Patent Application
20230333017
Image sensors are utilized for biological and chemical analysis. Various protocols in biological or chemical research involve performing controlled reactions on local support surfaces or within predefined reaction chambers. The designated reactions may then be observed or detected, and subsequent analysis may help identify or reveal properties of chemicals involved in the reaction. 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 well of a flow cell channel. Observing any chemical reactions that occur between the known probes and the unknown analyte within the wells 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.
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 analytes. Such optical systems may include an arrangement of lenses, filters, and light sources. In other detection systems, the controlled reactions occur immediately 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.
In some devices that provide fluorescent detection, including in those that utilize several wells (e.g., nanowells) or reaction sites, there may be a risk of crosstalk, where a sensor corresponding to one well or reaction site undesirably receives light from either another well or reaction site or some other source. It may therefore be beneficial, advantageous, and desirable to include features that eliminate or otherwise reduce the risk of such crosstalk. It may also be beneficial, advantageous, and desirable to provide such crosstalk reduction features without undesirably increasing the manufacturing cost or complexity of the device.
Accordingly, it may be beneficial to utilize a layer including germanium (e.g., silicon germanium, Si(x)Ge(1-x) or SixGe1-x), over the aforementioned sensor(s) (e.g., CCD and/or CMOS), for the purpose of loss induced crosstalk reduction (LICR). In various examples herein, resultant sensors (e.g., image sensors) can utilize a layer of germanium as both an emission filter (which blocks excitation light) and for LICR. Thus, in examples herein, one or more layers of germanium are utilized in biosensors to provide semiconductor filtering in addition to LICR.
Thus, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of a method for forming aspects of a biosensor. Various examples of the method are described below, and the method, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the method comprises: forming one or more diodes on a first surface of a substrate, wherein the first surface of the substrate is parallel to a second surface of the substrate; forming one or more trenches between the one or more diodes, the one or more trenches extending toward the second surface of the substrate from the first surface of the substrate, wherein the forming comprises filling the one or more trenches and planarizing the one or more filled trenches to form a first surface substantially parallel to a first surface of the one or more diodes and the first surface of the substrate; removing a portion of the substrate such that the one or more trenches extend through the substrate from the first surface of the substrate to the second surface of the substrate; bonding a carrier wafer to the second surface of the substrate; forming a germanium layer above the second surface of the substrate; and forming a dielectric stack above a surface of the germanium layer.
In some examples of the method, forming the one or more trenches comprises etching the one or more trenches in the substrate.
In some examples of the method, the substrate comprises silicon.
In some examples of the method, filling the one or more trenches comprises filling the one or more trenches with one or more dielectric layers.
In some examples of the method, the dielectric stack comprises one or more nanowells.
In some examples of the method, forming the germanium layer on the second surface of the substrate comprises depositing germanium on the second surface of the substrate.
In some examples of the method, a technique for the depositing is selected from the group consisting of: Plasma Enhanced Chemical Vapor Deposition (PECVD), sputter, e-beam evaporation, crystalline growth and etching, and radical activation bonding in vacuum.
In some examples of the method, the selected technique is crystalline growth and etching and the crystalline growth and etching comprises one of: transfer wafer bonding or direct wafer bonding.
In some examples of the method, forming the germanium layer above the second surface of the substrate further comprises: forming a first one or more dielectric layers on the second surface of the substrate; forming the germanium layer on a surface of the one or more dielectric layers; and forming a second one or more dielectric layers on a surface of the germanium layer.
In some examples of the method, the substrate, one or more diodes, the carrier wafer, and the one or more filled trenches comprise a sensor.
In some examples of the method, the sensor comprises a complementary metal-oxide-semiconductor (CMOS).
In some examples of the method, the germanium layer comprises germanium and silicon.
In some examples of the method, the stack comprises: one or more dielectric layers; and a sensor compatible metal.
In some examples of the method, the germanium layer performs loss induced crosstalk reduction and filters out excitation light when light source emits light toward the dielectric stack.
In some examples of the method, based on the loss induced crosstalk reduction, a signal at neighboring pixels is substantially lower than a signal at paired pixels.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of a method for forming aspects of a biosensor. Various examples of the method are described below, and the method, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the method comprises: forming a germanium layer above a top surface of an image sensor; and forming a dielectric stack above a top surface of the germanium layer.
In some examples of the method, the dielectric stack comprises one or more nanowells.
In some examples of the method, forming the germanium layer above the top surface of the image sensor further comprises: forming a first one or more dielectric layers on the top surface of the image sensor; forming the germanium layer on a surface of the one or more dielectric layers; and forming a second one or more dielectric layers on a surface of the germanium layer.
In some examples of the method, forming the germanium layer above the top surface of the image sensor comprises depositing germanium above the top surface of the image sensor.
In some examples of the method, a technique for the depositing is selected from the group consisting of: Plasma Enhanced Chemical Vapor Deposition (PECVD), sputter, e-beam evaporation, crystalline growth and etching, and radical activation bonding in vacuum.
In some examples of the method, the selected technique is crystalline growth and etching and the crystalline growth and etching comprises one of: transfer wafer bonding or direct wafer bonding.
In some examples of the method, the image sensor comprises a complementary metal-oxide-semiconductor (CMOS).
In some examples of the method, the image sensor comprises a backside image sensor with one or more deep trenches.
In some examples of the method, the germanium layer performs loss induced crosstalk reduction and filters out excitation light when light source emits light toward the dielectric stack.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of a method for utilizing a biosensor. Various examples of the method are described below, and the method, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the method comprises: obtaining a biosensor, the biosensor comprising: a germanium layer above a top surface of an image sensor; and a dielectric stack above a top surface of the germanium layer, wherein the dielectric stack comprises wells and reaction sites; placing one or more nucleic acids in the reaction sites; and exposing the reaction sites of the biosensor to light from a light source, wherein the light comprises excitation light and emitted light; obtaining, by the image sensor, the emitted light, from the reaction sites, via the germanium layer, the emitted light, wherein the germanium layer filters the excitation light from the light and reduces crosstalk associated with the emitted light; and identifying, by the image sensor, based on the emitted light, a composition of the nucleic acids.
In some examples of the method, the image sensor comprises one or more diodes.
In some examples of the method, the obtaining the emitted light, from the reaction sites, via the germanium layer further comprises: propagating the emitted light through the germanium layer at non-vertical angles to reach at least one diode of the one or more diodes.
In some examples of the method, the reaction sites comprise fluorophores, and wherein based on exposing the reaction sites of the biosensor to light from a light source, the excitation light causes the fluorophores to emit the emitted light.
In some examples of the method, the germanium layer comprises germanium and silicon.
In some examples of the method, the biosensor further comprises: a first one or more dielectric layers on the top surface of the image sensor; and a second one or more dielectric layers on a surface of the germanium layer.
In some examples of the method, the image sensor comprises a complementary metal-oxide-semiconductor (CMOS).
In some examples of the method, the germanium layer comprises germanium and silicon.
In some examples of the method, the dielectric stack comprises: one or more dielectric layers; and a sensor compatible metal.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of an apparatus that can be utilized as a biosensor. Various examples of the apparatus are described below, and the apparatus, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the apparatus comprises: a filter layer comprising germanium; a flow channel floor defining a plurality of wells, wherein each well provides a reaction site, wherein the filter layer is positioned under flow channel floor, wherein the filter layer spans contiguously under the plurality of wells.
In some examples, of the apparatus, the apparatus further comprises: a plurality of sensors positioned under the filter layer, each sensor of the plurality of sensors centered under a corresponding well and reaction site, such that each sensor forms a sensing pair with a corresponding reaction site.
In some examples, of the apparatus, the filter layer further comprises silicon.
In some examples, of the apparatus, the filter layer has a height of approximately 300 micrometers to approximately 500 micrometers.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of a method for utilizing a biosensor. Various examples of the method are described below, and the method, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the method comprises: placing one or more nucleic acids in reaction sites of an apparatus, the apparatus comprising: a filter layer comprising germanium; a flow channel floor defining a plurality of wells, wherein each well provides a reaction site of the reaction sites, wherein the filter layer is positioned under flow channel floor; wherein the filter layer spans contiguously under the plurality of wells; exposing the reaction sites of the apparatus to light from a light source, wherein the light comprises excitation light and emitted light; receiving the emitted light from the reaction sites via the filter layer, wherein the filter layer filters the excitation light from the light and reduces crosstalk associated with the emitted light; and identifying, based on the emitted light, a composition of the one or more nucleic acids.
In some examples of the method, the apparatus includes a plurality of sensors positioned under the filter layer, each sensor of the plurality of sensors centered under a corresponding well and another reaction site of the reaction sites, such that each sensor forms a sensing pair with a corresponding reaction site.
In some examples of the method, the filter layer of the apparatus further comprises silicon.
In some examples of the method, the filter layer has a height of approximately 300 micrometers to approximately 500 micrometers.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of a method for forming aspects of a biosensor. Various examples of the method are described below, and the method, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the method comprises: forming a germanium layer over a top surface of a sensor, wherein the sensor comprises: a substrate comprising one or more diodes; a first oxide layer formed over a top surface of the substrate; forming a first conductive layer over a top surface of the germanium layer; forming a second oxide layer over a top surface of the first conductive layer; forming a second conductive layer over a top surface of the second oxide layer; depositing photoresist on a first portion of a top surface of the second conductive layer; and etching through a second portion of the top surface of the second conductive layer, wherein the photoresist is not deposited on the second portion of the top surface of the second conductive layer, a portion of the second oxide layer, and a portion of the first conductive layer, wherein the etching forms one or more trenches, wherein the one or more trenches are each positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the second oxide layer.
In some examples of the method, the germanium layer further comprises silicon, and forming the germanium layer comprises sputtering silicon-germanium onto the top surface of the first oxide layer.
In some examples of the method, the one or more trenches comprise nanowells.
In some examples of the method, forming the germanium layer over a top surface of a sensor further comprises: depositing photoresist on a first portion of the top surface of the first oxide layer; etching through a second portion of the top surface of the first oxide layer, wherein the photoresist is not deposited on the second portion of the top surface of the first oxide layer, wherein the etching forms one or more trenches in the first oxide layer; depositing a crosstalk mitigating substance above the first oxide layer, wherein the depositing fills the one or more trenches in the first oxide layer; planarizing the crosstalk mitigating substance such that a portion of the crosstalk mitigating substance forms a contiguous surface with the first portion of the top surface of the first oxide layer; and depositing a layer of silicon germanium on the top surface of the first oxide layer.
In some examples of the method, the crosstalk mitigating substance is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the method, the method also includes: forming a passivation layer over the first portion of the top surface of the second conductive layer.
In some examples of the method, forming the germanium layer over a top surface of a sensor further comprises: sputtering an additional conductive layer on the top surface of the first oxide layer; depositing photoresist on a first portion of the additional conductive layer, wherein the second portion of the first oxide layer is exposed; removing a second portion of the additional conductive layer with etching, wherein the photoresist is not deposited on the second portion of the additional conductive layer, wherein based on the removing, the top surface of the first oxide layer and the first portion of the additional conductive layer are exposed; and depositing a layer of silicon germanium on the top surface of the first oxide layer.
In some examples of the method, forming the germanium layer over a top surface of the sensor comprises: depositing photoresist on a first portion of the top surface of the first oxide layer; etching through a second portion of the top surface of the first oxide layer, wherein the photoresist is not deposited on the second portion of the top surface of the first oxide layer, wherein the etching forms one or more trenches in the first oxide layer; depositing the germanium layer above the first oxide layer, wherein the depositing partially fills the one or more trenches in the first oxide layer; depositing a crosstalk mitigating substance above the germanium layer, wherein the depositing fills a remainder of the one or more trenches in the first oxide layer; and planarizing the crosstalk mitigating substance such that the top surface of the germanium layer is a contiguous surface comprising a portion of the crosstalk mitigating substance and the first portion of the top surface of the first oxide layer.
In some examples of the method, the crosstalk mitigating substance is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the method, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the method includes: forming a silicon layer on the top surface of the second oxide layer.
In some examples of the method, the first conductive layer and the second conductive layer are comprised of metal.
In some examples of the method, the first oxide layer comprises electrically conductive materials.
In some examples of the method, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of a method for forming aspects of a biosensor. Various examples of the method are described below, and the method, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the method comprises: forming a germanium layer over a top surface of a sensor, wherein the sensor comprises: a substrate comprising one or more diodes; a first oxide layer formed over a top surface of the substrate, wherein forming the germanium layer comprises: depositing photoresist on a first portion of a top surface of the germanium layer; and etching through a second portion of the top surface of the germanium layer, wherein the photoresist is not deposited on the second portion of the top surface of the germanium, wherein the etching forms one or more trenches, wherein the trenches are each positioned above a space between at least one diode and another diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the germanium layer; forming a second oxide layer over a top surface of the germanium layer; depositing photoresist on a first portion of a top surface of the second oxide layer; and etching through a second portion of the top surface of the second oxide layer, wherein the photoresist is not deposited on the second portion of the top surface of the second oxide layer, wherein the etching forms an additional one or more trenches, wherein the additional one or more trenches are each positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the second oxide layer.
In some examples of the method, the method includes: forming a silicon layer over the top surface of the second oxide layer.
In some examples of the method, forming the germanium layer over the top surface of the sensor further comprises: depositing silicon germanium on the top surface of the first oxide layer; depositing a conductive layer on the silicon germanium; and depositing photoresist on a first portion of the conductive layer; and etching through a second portion of the conductive layer, wherein the photoresist is not deposited on the second portion of the conductive layer, wherein the etching removes the second portion of the conductive layer, and wherein the top surface germanium layer comprises a surface comprising a portion of the silicon germanium and the first portion of the conductive layer.
In some examples of the method, the method includes: depositing a conductive layer on the top surface of the second oxide layer; depositing photoresist on a first portion of the conductive layer; and etching through a second portion of the conductive layer, wherein the photoresist is not deposited on the second portion of the conductive layer, wherein the etching removes the second portion of the conductive layer.
In some examples of the method, forming the germanium layer over the top surface of the sensor further comprises: depositing silicon germanium on the top surface of the first oxide layer; depositing a conductive layer on the top surface of the silicon germanium; depositing photoresist on a first portion of the conductive layer; and etching through a second portion of the conductive layer, wherein the photoresist is not deposited on the second portion of the conductive layer, wherein the etching removes the second portion of the conductive layer, and where the top surface of the germanium layer comprises the first portion of the conductive layer and a portion of the silicon germanium.
In some examples of the method, forming the germanium layer over the top surface of the sensor further comprises: depositing a conductive layer on the top surface of the sensor; depositing photoresist on a first portion of the conductive layer; and etching through a second portion of the conductive layer, wherein the photoresist is not deposited on the second portion of the conductive layer, wherein the etching removes the second portion of the conductive layer; and depositing silicon germanium over a portion of the first oxide layer and the first portion of the conductive layer.
In some examples of the method, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the first oxide layer comprises conductive components.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of an apparatus comprising a biosensor. Various examples of the apparatus are described below, and the apparatus, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the apparatus comprises: a sensor comprising: a substrate comprising one or more diodes; a first oxide layer formed over a top surface of the substrate; a germanium layer formed over a top surface of the sensor; a first conductive layer formed over a top surface of the germanium layer; a second oxide layer formed over a top surface of the first conductive layer; a second conductive layer formed over a top surface of the second oxide layer, wherein the second conductive layer, the second oxide layer, and the first conductive layer comprise one or more trenches, and wherein the one or more trenches are each positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the second oxide layer.
In some examples of the apparatus, the germanium layer further comprises silicon.
In some examples of the apparatus, the one or more trenches comprise nanowells.
In some examples of the apparatus, the first oxide layer comprises an oxide substance and a crosstalk mitigating substance, wherein the crosstalk mitigating substance fills trench structures in the oxide substance.
In some examples of the apparatus, the crosstalk mitigating substance is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the apparatus, the apparatus includes: a passivation layer formed over the first portion of the top surface of the second conductive layer.
In some examples of the apparatus, the germanium layer comprises: an additional conductive layer over the top surface of the first oxide layer, wherein the additional and conductive layer comprises fissures; and a layer of silicon germanium over the top surface of the first oxide layer.
In some examples of the apparatus, the first oxide layer comprises trench structures, wherein the top surface of the sensor is an uneven surface and the germanium layer formed over a top surface of the sensor comprises: silicon germanium filling a portion of the trench structures; and a crosstalk mitigating substance filling a remainder of the trench structures, wherein the top surface of the germanium layer is a contiguous surface comprising a portion of the crosstalk mitigating substance and a portion of a top surface of the first oxide layer.
In some examples of the apparatus, the crosstalk mitigating substance filling the remainder of the trench structures is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the apparatus, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the apparatus, the oxide layer comprises electrically conductive materials.
In some examples of the apparatus, the apparatus includes: a silicon layer on the top surface of the second oxide layer.
In some examples of the apparatus, the first conductive layer and the second conductive layer are comprised of metal.
In some examples of the apparatus, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the apparatus, the apparatus includes a pixel pitch of less than one micron.
In some examples of the apparatus, the germanium layer is of a thickness of less than 400 nm.
In some examples of the apparatus, the germanium layer is of a thickness between approximately 300 nm and approximately 330 nm.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of an apparatus comprising a biosensor. Various examples of the apparatus are described below, and the apparatus, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the apparatus comprises: a sensor comprising: a substrate comprising one or more diodes; and a first oxide layer formed over a top surface of the substrate; a germanium layer over a top surface of a sensor, wherein the germanium layer comprises one or more trenches positioned above a space between at least one diode and another diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the germanium layer; and a second oxide layer over a top surface of the germanium layer, wherein the second oxide layer fills the trenches in the germanium layer, wherein the second oxide layer comprises one or more trenches, each trench in the second oxide layer positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to a top surface of the second oxide layer, wherein the trenches in the second oxide layer expose portions of the germanium layer.
In some examples of the apparatus, the apparatus includes: a silicon layer over the top surface of the second oxide layer.
In some examples of the apparatus, the apparatus includes: a conductive layer comprising lining the one or more trenches in the germanium layer.
In some examples of the apparatus, the apparatus includes: a conductive layer over the top surface of the second oxide layer.
In some examples of the apparatus, the apparatus includes: a conductive layer over the top surface of the sensor.
In some examples of the apparatus, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the apparatus, the first oxide layer comprises conductive components.
In some examples of the apparatus, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the apparatus, the apparatus includes: a pixel pitch of less than one micron.
In some examples of the apparatus, the germanium layer is of a thickness of less than 400 nm.
In some examples of the apparatus, the germanium layer is of a thickness of less than 300 nm.
In some examples of the apparatus, the germanium layer is of a thickness between approximately 300 nm and approximately 330 nm.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of a method for utilizing a biosensor. Various examples of the method are described below, and the method, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the method comprises: placing one or more nucleic acids in reaction sites of a sensor, the sensor comprising: a substrate comprising one or more diodes; and a first oxide layer formed over a top surface of the substrate; a germanium layer over a top surface of the first oxide layer, wherein the germanium layer comprises one or more trenches positioned above a space between at least one diode and another diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the germanium layer; and a second oxide layer over a top surface of the germanium layer, wherein the second oxide layer fills the trenches in the germanium layer, wherein the second oxide layer comprises one or more trenches, each trench in the second oxide layer positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to a top surface of the second oxide layer, wherein the trenches in the second oxide layer expose portions of the germanium layer, wherein the second oxide layer comprises wells and the reaction sites; exposing the reaction sites of the sensor to light from a light source, wherein the light comprises excitation light and emitted light; receiving, by the one or more diodes, the emitted light from the reaction sites via the germanium layer, wherein the germanium layer filters the excitation light from the light and reduces crosstalk associated with the emitted light; and identifying, based on the emitted light, a composition of the nucleic acids.
In some examples of the method, the sensor further comprises: a conductive layer on the top surface of the sensor.
In some examples of the method, receiving the emitted light from the reaction sites via the germanium layer further comprises: propagating the emitted light through the germanium layer to reach at least one diode of the one or more diodes.
In some examples of the method, the reaction sites comprise fluorophores, and wherein based on exposing the reaction sites of the sensor to light from a light source, the excitation light causes the fluorophores to emit the emitted light.
In some examples of the method, the germanium layer comprises germanium and silicon.
In some examples of the method, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the sensor further comprises: a silicon layer over the top surface of the second oxide layer.
In some examples of the method, the sensor further comprises: a conductive layer comprising lining the one or more trenches in the germanium layer.
In some examples of the method, the sensor further comprises: a conductive layer over the top surface of the second oxide layer.
As aforementioned, shortcomings of the prior art can be overcome and benefits as described later in this disclosure can be achieved through the provision of a method for utilizing a biosensor. Various examples of the method are described below, and the method, including and excluding the additional examples enumerated below, in any combination (provided these combinations are not inconsistent), overcome these shortcomings. In some examples herein, the method comprises: placing one or more nucleic acids in reaction sites of a biosensor, the biosensor comprising: a sensor, the sensor comprising: a substrate comprising one or more diodes; and a first oxide layer formed over a top surface of the substrate; a germanium layer formed over a top surface of the sensor; a first conductive layer formed over a top surface of the germanium layer; a second oxide layer formed over a top surface of the first conductive layer; a second conductive layer formed over a top surface of the second oxide layer, wherein the second conductive layer, the second oxide layer, and the first conductive layer comprise one or more trenches, and wherein the one or more trenches are each positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the second oxide layer, wherein the trenches comprise wells and reaction sites; exposing the reaction sites of the biosensor to light from a light source, wherein the light comprises excitation light; receiving, by the one or more diodes, the emitted light from the reaction sites via the germanium layer, wherein the germanium layer filters the excitation light and reduces crosstalk associated with the emitted light; and identifying, based on the emitted light, a composition of the nucleic acids.
In some examples of the method, the germanium layer further comprises silicon.
In some examples of the method, the first oxide layer comprises an oxide substance and a crosstalk mitigating substance, and the crosstalk mitigating substance fills trench structures in the oxide substance.
In some examples of the method, the crosstalk mitigating substance is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the method, the biosensor further comprises: a passivation layer formed over the first portion of the top surface of the second conductive layer.
In some examples of the method, the germanium layer comprises: an additional conductive layer over the top surface of the first oxide layer, wherein the additional and conductive layer comprises fissures; and a layer of silicon germanium over the top surface of the first oxide layer.
In some examples of the method, the first oxide layer comprises trench structures, wherein the top surface of the sensor is an uneven surface and the germanium layer formed on a top surface of the sensor comprises: silicon germanium filling a portion of the trench structures; and a crosstalk mitigating substance filling a remainder of the trench structures, wherein the top surface of the germanium layer is a contiguous surface comprising a portion of the crosstalk mitigating substance and a portion of a top surface of the first oxide layer.
In some examples of the method, the crosstalk mitigating substance filling the remainder of the trench structures is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the method, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the oxide layer comprises electrically conductive materials.
In some examples of the method, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the obtaining the emitted light from the reaction sites, via the germanium layer further comprises: propagating the emitted light through the germanium layer to reach at least one diode of the one or more diodes.
In some examples of the method, the reaction sites comprise fluorophores, and wherein based on exposing the reaction sites of the sensor to light from a light source, the excitation light causes the fluorophores to emit the emitted light.
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.
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.
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 in which:
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 part 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 are 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.
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.
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 small fluctuations 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%.
As used herein, a “flow cell” can include a device optionally having a lid extending over a reaction structure to form a flow channel therebetween that is in communication with a plurality of reaction sites (e.g., nanowells) of the reaction structure, and can optionally include a detection device that detects designated reactions that occur at or proximate to the reaction sites. 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, the image sensor structure of a sensor system 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. As another specific example, 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 diodes (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 flow cell.
Flow cells described herein perform various biological or chemical processes. More specifically, the flow cells 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, flow cells described herein 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.
The flow cells facilitate a plurality of designated reactions that may be detected individually or collectively. The flow cells perform numerous cycles in which the plurality of designated reactions occurs in parallel. For example, the flow cells 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 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 be, 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 cells, the reaction sites may be located in reaction recesses or chambers, which may at least partially compartmentalize the designated reactions therein.
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 particular flow cells, 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 flow cells, 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 another example of flow cells, the detected fluorescence is a result of chemiluminescence or bioluminescence. A designated reaction may also increase fluorescence (or Förster) 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.
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.
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.
As used herein, the term “reaction site” is a localized region where at least one designated reaction may occur. Reaction sites in the context of the biosensors described herein can also be referred to as nanowells. A reaction site may include support surfaces of a reaction structure or substrate where a substance may be immobilized thereon. For example, 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 flow cells, 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 flow cells a reaction site may contain only a single nucleic acid molecule, for example, in a single stranded or double stranded form.
The terms “active surface” and “active area” are used herein to characterize a surface or area of a reaction structure which operates to support one or more designation reactions. Throughout this disclosure, the terms die and wafer are also used in reference to certain examples herein, as a die can include a sensor and the die is fabricated from a wafer. The words wafer and substrate are also used interchangeably herein.
Examples described herein may be used in various biological or chemical processes and systems for 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.
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.
In some examples, the wells or reaction sites are randomly distributed across a substantially planar 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 substantially planar 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.
In some examples, image sensors may detect light emitted from wells (e.g., nanowells) or reaction sites and the signals indicating photons emitted from the wells or reaction sites and detected by the individual image sensors may be referred to as 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 referred to as 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 referred to as a sharpened image.
In some examples, image sensors (e.g., photodiodes) are associated with corresponding wells or reaction sites. 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 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.
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 is an array, generates a signal. The sensors discussed in the examples herein, which can include image sensors can include front side illuminated sensors (FSIs) and back-side illuminated sensors (BSIs).
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 first reaction 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.
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.
As used herein, the term loss-induced crosstalk reduction or “LICR” refers to a tailored absorption of light that might otherwise result in crosstalk. While certain LICR features may not eliminate crosstalk, as discussed herein, they can reduce it to a degree where any remaining crosstalk may be computationally corrected through conventional image processing techniques (where such image processing techniques, alone, may be insufficient in the absence of the LICR features described herein). Based on LICR, a signal at neighboring pixels is substantially lower than a signal at paired pixels.
As used herein the term “emission 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. 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).
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) wafer (substrate) is exposed to one or more volatile precursors, which react and/or decompose on the substrate surface to produce a desired deposit. As discussed herein, 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. In the context of the examples herein, CVD and/or specifically PECVD is utilized to deposit an oxide layer with a low index of refraction (referred to also as a low index oxide layer, e.g., SiO (silicon monoxide)) on certain of the apparatuses discussed. This description also includes references to high index oxide materials, which refer to materials with a high index of refraction, including but not limited to SiN (silicon nitride).
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.
Various examples herein include a layer of germanium. Some examples reference silicon germanium SiGe, specifically. This example is provided for illustrative purposes and the germanium layers referenced, in various examples, can comprise silicon germanium, Si(x)Ge(1-x) or SixGe1-x).
Reference is made below to the drawings, which are not 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. To the extent that the figures illustrate diagrams of the functional blocks of various examples, the functional blocks are not necessarily indicative of the division between hardware components. Thus, for example, one or more of the functional blocks (e.g., processors or memories) may be implemented in a single piece of hardware (e.g., a general-purpose signal processor or random-access memory, hard disk, or the like). Similarly, the programs may be standalone programs, may be incorporated as subroutines in an operating system, may be functions in an installed software package, and the like. The various examples are not limited to the arrangements and instrumentality shown in the drawings.
It is desirable to reduce crosstalk in sensors, including in biosensors utilized in flow cells as crosstalk adversely affects performance. A traditional way in which crosstalk can be reduced in an apparatus with an image sensor, such as a flow cell, is by physically constraining transmission of light by embedding various light guides in the sensor, including but not limited to curtain structures, light pipes, and/or optical waveguides and/or microlenses. These structures direct light emitted from a corresponding reaction site directly downwardly toward an image sensor that forms a sensing pair with the reaction site. As will be described herein in reference to
Because of the manufacturing complexities and structural limitations associated with sensor devices that include structural elements (e.g., curtain structures, light pipes, and/or optical waveguides) 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 distance, which will be discussed herein. Rather than integrate what are sometimes complex structures into sensing devices to reduce crosstalk, such as the aforementioned curtain structures, light pipes, and/or optical waveguides, which increase the cost and complexity of the sensor devices, examples of sensor devices, also referred to herein as biosensors, described herein instead include at least one layer of germanium that provides LICR and/or an emission filter. LICR features, such as the germanium layer, integrated into biosensors described herein do not completely eliminate crosstalk, but, rather, provide tailored absorption of light that might otherwise result in crosstalk. LICR examples 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 in a biosensor. Utilizing layers to reduce crosstalk, rather than structures, such as that in
As discussed on
Described herein are structures of examples of sensor devices (e.g., biosensors) which include this at least one germanium layer for LICR and as an emission filter, methods of using these sensor devices, and methods of manufacturing these sensor devices. Manufacturing examples herein include both biosensors that include from an off-the-shelf sensor components, such as an off-the shelf-CMOS, as well as methods that involve forming a custom sensor or CMOS. As noted above, utilizing a sensor device with a germanium layer for LICR instead of a complex structure (e.g., curtain structures, light pipes, and/or optical waveguides) reduces development cost and turn-around time of sensor-based sequencers, including, but not limited to, CMOS-based sequencers. The methods of manufacture utilized to manufacture sensors with curtain structures, light pipes, and/or optical waveguides, involve a high level of customization, increase cost, and, from a performance perspective, add difficulty to increasing reaction site density, when compared with method of manufacture of biosensors with the aforementioned germanium layer.
To contrast existing biosensors that utilize structural elements spanning the height of the biosensors for crosstalk reduction and the examples herein which utilize a layer of germanium for LICR and as an emission filter,
As biosensor 100 is exposed to excitation light 101 (e.g., as generated by one or more light sources), the excitation light 101 causes fluorophores at reaction sites 114 to emit light 111. The filter material 132 filters out the excitation light 101 without filtering out the emitted light 111. In scenarios where nucleic acids are at reaction sites 114, the emitted light 111 may indicate the composition of such nucleic acids. An image sensor 150 is positioned under each light guide 130 and is configured to receive the light 111 emitted from the corresponding reaction site 114 via the corresponding light guide 130. Thus, each image sensor 150 forms a “sensing pair” with the reaction site 114 that is directly aligned with (e.g., positioned directly above) the image sensor 150. In versions where each image sensor 150 represents a single pixel, the image sensor 150 forming a sensing pair with a reaction site 114 may be referred to as the “center pixel” associated with that reaction site 114; while the image sensors 150 adjacent to the center pixel may be referred to as “neighbor pixels.” Similarly, an image sensor 150 that does not form a sensing pair with a given reaction site 114 may be referred to as a “neighbor sensor” with respect to that reaction site 114.
In some other examples, a single image sensor 150 may receive photons through more than one light guide 130 and/or from more than one reaction site 114. In such versions, the particular region of the single image sensor 150 that is directly aligned with (e.g., positioned directly under) a reaction site 114 may be said to form a “sensing pair” with that reaction site 114.
As shown in
The biosensor 100 depicted in
The integration of curtains 140 into a biosensor 100 may effectively prevent optical crosstalk within the biosensor 100 by suitably preventing light 111 emitted at a reaction site 114 from reaching an image sensor 150 that does not form a sensing pair with the reaction site 114. However, as noted above generally and demonstrated in this non-limiting example, including curtains 140 in a biosensor 100 may tend to add complexity and expense to the process of manufacturing biosensor 100, especially with curtains 140 extending through the full height distance (H) of biosensor 100. Such complexity and expense may be due, at least in part, to curtains 140 having sub-micron feature sizes (in the x-y plane) and several-micron thickness (in the z direction). Such complexity and expense may also be due, at least in part, to filter material 460 being applied separately within each individual light guide 462.
In addition, it may be desirable to minimize the pitch distance (P) in a biosensor 100 in order to maximize the total number of reaction sites 114 in the biosensor 100 (e.g., to maximize the density of reaction sites 114 in biosensor 100); and the presence of curtains 140 in a biosensor 100 may constrain the reduction of pitch distance (P) in the biosensor 100 since curtains 140 occupy physical space in the biosensor. Thus, it is possible to reduce the pitch distance (P) in the biosensor 100 if curtains 140 are eliminated.
As biosensor 200 is exposed to excitation light 201 (e.g., as generated by one or more light sources), the excitation light 201 causes fluorophores at reaction sites 214 to emit light 211. In scenarios where nucleic acids are at reaction sites 214, the emitted light 211 may indicate the composition of such nucleic acids. Image sensors 250 receive the light 211 emitted from the reaction sites 214 via the layer 232 of filter material. The filter material of layer 232 filters out the excitation light 201 without filtering out the emitted light 211. As will be discussed herein, including in
Since biosensor 200 of the example shown in
The distribution of an optical signal from light 211 emitted from a single reaction site 214 over the image sensors 250 of biosensor 200 may be defined as a point-spread function (PSF). The PSF may thus represent the degree of crosstalk occurring within biosensor 200. The PSF may depend on the height-to-pitch ratio (HIP), as shown below in Equation I:
In this non-limiting example, the reaction sites 314 and wells 312 are comprised of multiple oxide layers and/or of another dielectric material (e.g., NiO, SiO2, tantalum pentoxide, Si3N4, etc.) 328 and a sensor (e.g., CMOS) compatible metal (e.g., aluminum, tantalum, etc.) 326. By way of example and not to impose or suggest any limitations, the compatible metal 326 can be approximately 200 to approximately 500 nm.
An image sensor 355 (e.g., a backside image sensor with deep trenches) is positioned under the layer 332 that includes germanium. This layer 332 serves as both a filter layer and a LICR layer. In this example, between the layer 332 and the sensor 355 is one or more layers of isolation oxide and/or of another dielectric material (e.g., SiO2, NiO, Si3N4, etc.) 324. One or more layers of isolation oxide and/or of another dielectric material (e.g., SiO2, NiO, Si3N4, etc.) 324 are also situated between the layer 332 and the multiple oxide layers and/or layers of another dielectric material (e.g., NiO, SiO2, Si3N4, tantalum pentoxide, etc.) 328 and the sensor (e.g., CMOS) compatible metal (e.g., aluminum, tantalum, etc.) 326, below the base of the latter. Although not pictured in
As biosensor 300 is exposed to excitation light 301 (e.g., as generated by one or more light sources), the excitation light 301 causes fluorophores at reaction sites 314 to emit light 311. In scenarios where nucleic acids are at reaction sites 314, the emitted light 311 may indicate the composition of such nucleic acids. The image sensor 355 receives light emitted from the reaction sites 314 via the layer 332 of filter material. The filter material of layer 332 filters out the excitation light 301 without substantially filtering out the emitted light. The layer 332 of filter material suitably prevents transmission of substantially all or all wavelengths of excitation light 301 while permitting transmission of all or substantially all wavelengths of emitted light. As is the case with the biosensor of
As discussed above, an advantage of eliminating complex structures for crosstalk reduction or elimination, such as the curtains 140 of
As noted above,
Germanium and composite materials that include germanium can be utilized effectively in biosensors for LICR and as an emission filter at least because properties of germanium and of silicon germanium, including the absorption coefficient of these materials are conducive to this use.
Turning first to
In Equation II, QE is an emission or excitation wavelength. Thus. QEred is the emission wavelength of red while QEgreen is the excitation wavelength of green. H represents the thickness of the germanium and Δa=ared−agreen=300,000 1/cm.
Thus, H, the thickness of the germanium, can be represented by Equation III.
Thus, when the absorption of red and green is compared, it is greater than 105, as illustrated in Equation IV below.
When the calculations in this non-limiting example are complete the thickness, H, is found to be greater than 360 nanometers, as illustrated in Result V below.
H>360 nm (V)
The thickness of the germanium layer utilized in various examples of the biosensors described herein is selected based on a relationship between excitation wavelength QE (e.g., green and blue) and emission wavelength QE (e.g., red). To optimize functionality is some examples of the biosensors described herein, the germanium layer would increase red QE and reduce blue and green QE. For the purpose of ease in fabrication combined with performance gains, it is desirable to utilize a layer of the lowest thickness that gives a high enough
ratio to act as an effective emission filter. Higher thickness improves
but reduces the absolute amount of QEred, which can adversely affect the operation of the biosensor. Thus, an optimum value for the thickness would cause the layer to operate as a filter that performs enough excitation rejection (the ratio) and receives enough of the signal (red QE). In some examples, this optimum value for thickness is expressed as
Now turning to
As discussed above, biosensors that include germanium (e.g., silicon germanium, Si(x)Ge(1-x)) can be fabricated utilizing various methods discussed herein. However, certain of the methods can include fabricating an image sensor (e.g., CMOS) as a custom part of the biosensor while other methods can utilize off-the-shelf image sensors and deposit a germanium layer. Non-limiting examples of both types of fabrication/manufacturing processes are illustrated herein.
Referring to
The workflow 800 also includes forming one or more trenches between the one or more diodes (820). These trenches extend toward the second surface of the substrate from the first surface of the substrate. Various methods can be utilized to form these trenches, including but not limited to etching the one or more trenches in the substrate.
The workflow 800 includes forming a first surface substantially parallel to a first surface of the diodes and the first surface of the substrate by filling the trenches and planarizing the filled trenches (830). In some examples, the trenches are filled with one or more oxide layers and/or one or more dielectric layers (which do not include oxide). As noted above, some methods of forming or manufacturing examples of the biosensors described herein, which include at least one layer with germanium for LICR and filtering, start with a pre-existing sensor while others include forming the sensor.
The workflow 800 can include removing a portion of the substrate such that the trenches extend through the substrate from the first surface of the substrate to the second surface of the substrate (840). The workflow 800 includes bonding a carrier wafer to the second surface of the substrate (850). In some examples, the carrier wafer is bonded to the surface of the substrate before a portion of the substrate is removed and in others, the portion of the substrate is removed before bonding the carrier wafer to this sensor structure. The workflow 800 of
The workflow 800 includes forming a germanium layer above the second surface of the substrate (860). The layer can be formed utilizing various techniques. For example, one can deposit the germanium layer on the surface of the substrate. One non-limiting technique that can be utilized to deposit this germanium is Plasma-enhanced chemical vapor deposition (PECVD). PECVD is a chemical vapor deposition process used to deposit thin films from a gas state (vapor) to a solid state on a substrate. As part of this process plasma is created, for example, by radio frequency (RF) (alternating current (AC)) frequency or direct current (DC) discharge between two electrodes, the space between which is filled with the reacting gases. In some examples, one deposits the germanium layer at a low temperature (e.g., ˜200-˜300 C) as part of the PECVD process. Other techniques that can be utilized to deposit the germanium layer (a layer that includes germanium but can also include silicon, as explained above) include, but are not limited to, sputter, e-beam evaporation, crystalline growth and etching, and radical activation bonding in vacuum. In some examples, when crystalline growth and etching is utilized, this includes either transfer wafer bonding or direct wafer bonding. Table 1 below lists various of the deposition techniques discussed earlier that can be utilized in various examples to deposit a germanium layer above the second surface of the substrate. In each case, the technique, the material, and a non-limiting example of one or more approximate temperatures is provided.
Returning to
Referring to
As mentioned when
Referring to
Returning to
As illustrated in
In contrast to
A dielectric stack 1225 is formed on a top surface of the sensor package (1130). For example, the dielectric can be formed, in some examples, on the germanium layer 1232. In other examples, an additional one or more layers of isolation oxide and/or of another dielectric material (e.g., SiO2, NiO, Si3N4, etc.) 1224 are formed over the germanium layer 1232, forming a barrier between the germanium layer 1232 and a dielectric stack 1225. Thus, in these examples, the dielectric stack is formed on a top layer of these additional one or more layers of isolation oxide and/or of another dielectric material (e.g., SiO2, NiO, Si3N4, etc.) 1224. In some examples, the dielectric stack 1225 is comprised of multiple oxide layers and/or of another dielectric material (e.g., NiO, SiO2, Si3N4, tantalum pentoxide, etc.) 1228 and sensor compatible metal (e.g., aluminum, tantalum, etc.) 1236. The dielectric stack 1225 includes wells 1212 and reaction sites 1214. The sensor 1255 can comprise one or more sensors which are vertically centered under a corresponding well 1212 and reaction site 1214, such that each sensor forms sensing pair with a corresponding reaction site 1214. In the resultant biosensor 1203 of
It is desirable to reduce crosstalk in sensors, including in biosensors utilized in flow cells, as crosstalk adversely affects performance. A traditional way in which crosstalk can be reduced in an apparatus with an image sensor, such as a flow cell, is by physically constraining transmission of light by embedding various light guides in the sensor, including but not limited to curtain structures, light pipes, and/or optical waveguides and/or micro-lenses. These structures 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 reduce crosstalk by physically blocking light to provide tailored absorption of light that might otherwise result in crosstalk. As is the case with the LICR layer, discussed in later examples, the physical structures reduce crosstalk.
Because of the manufacturing complexities and structural limitations associated with sensor devices that include structural elements (e.g., curtain structures, light pipes, and/or optical waveguides) 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 distance, which will be discussed herein. Rather than integrate what are sometimes complex structures into sensing devices to reduce crosstalk, such as the aforementioned curtain structures, light pipes, and/or optical waveguides, which increase the cost and complexity of the sensor devices, examples of sensor devices, also referred to herein as biosensors, described herein instead include at least one layer of germanium that provides LICR and/or an emission filter. LICR features, such as the germanium layer, integrated into biosensors described herein do not completely eliminate crosstalk, but, rather, provide tailored absorption of light that might otherwise result in crosstalk. LICR examples 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 in a biosensor. Utilizing layers to reduce crosstalk, rather than structures, provide blankets that are uniform in the x-y plane.
Described herein are structures of examples of sensor devices (e.g., biosensors) which include this at least one germanium layer for LICR and as an emission filter, methods of using these sensor devices, and methods of manufacturing these sensor devices. Manufacturing examples herein include both biosensors that include off-the-shelf sensor components, such as an off-the shelf-CMOS, as well as methods that involve forming a custom sensor or CMOS. As noted above, utilizing a sensor device with a germanium layer for LICR instead of a complex structure (e.g., curtain structures, light pipes, and/or optical waveguides) reduces development cost and turn-around time of sensor-based sequencers, including, but not limited to, CMOS-based sequencers. The methods of manufacture utilized to manufacture sensors with curtain structures, light pipes, and/or optical waveguides, involve a high level of customization, increase cost, and, from a performance perspective, add difficulty to increasing reaction site density, when compared with methods of manufacture of biosensors with a germanium layer. The off-the-shelf-sensors utilized in the examples herein include both FSI and BSI sensors.
In various traditional crosstalk mitigation methods, the structures include one or more of an organic filter and/or a metallic curtain that surrounds the organic filter to reduce crosstalk. In lieu of this organic filter and/or other structural elements spanning the height of the biosensors for crosstalk reduction (e.g., curtain structures, light pipes, and/or optical waveguides) to reduce crosstalk, the examples herein employ germanium (in a non-limiting example, ˜300-˜330 nm) as a filter and LICR medium. Some benefits and advantages of the methods and apparatuses described herein over biosensors with the aforementioned organic filter and/or complex structures are that: 1) the devices produced using the methods described herein can employ off-the-shelf image sensors (including both FSI and BSI sensors); 2) the methods herein are less complex and thus produce devices with fewer complexities; 3) the devices produced with the methods described herein can enable further density increases while shrinking pixel pitch; and 4) based on the methods producing less complex devices and producing them with fewer complex steps, supply chain risks are reduced. Other benefits and advantages may be discussed herein or may be apparent from this disclosure. One of the reasons that germanium is effective in crosstalk reduction in biosensors is that it has a high absolute difference in absorption between red and green. Other materials with similar high absolute difference in absorption between different ranges of wavelengths, for example, between red and green, may be suitable.
Examples herein include both BSI and FSI sensors or chips that are utilized as a base for fabricating a biosensor.
Examples herein have various similarities in both structure and method of manufacture, regardless of whether the base sensor is a BSI sensor or an FSI sensor. For this reason, examples of off-the shelf sensors that can be integrated into these examples are illustrated in
Certain examples herein are depicted with nanowells, however, nanowells are only one example of structures that can be utilized atop a biosensor to accomplish various aspects of the functionalities of the biosensors. Thus, when the examples herein depict nanowells, one of skill in the art will understand that different structures can be substituted as the nanowells as they may not be required or alternative structures may prove suitable in certain implementations.
Whether the sensor utilized in the resultant biosensor is a BSI sensor or an FSI sensor, certain of the techniques for fabricating the examples herein are similar if not identical. Before discussing various examples and the specifics of fabricating these examples,
As illustrated in
The germanium layer can include silicon. Various techniques can be utilized to form this germanium layer in different examples. For example, the layer can be formed by sputtering silicon-germanium onto the top surface of the first oxide layer (the oxide layer included in the sensor).
In other examples, the germanium layer on the sensor is formed by a combination of aspects. First, one can deposit photoresist on a first portion of the top surface of the first oxide layer. Then, one can etch through a second portion of the top surface of the first oxide layer (the photoresist is not deposited on the second portion of the top surface of the first oxide layer) to form one or more trenches in the first oxide layer.
Once the etching is complete, one can deposit a crosstalk mitigating substance above the first oxide layer (e.g., oxide, nitride, and silicon), which includes filling the one or more trenches in the first oxide layer. One can planarize the crosstalk mitigating substance such that a portion of the crosstalk mitigating substance forms a contiguous surface with the first portion of the top surface of the first oxide layer. One can then remove the photoresist. Once the photoresist (which preserved the surface as described) is removed, one can deposit a layer of silicon germanium on the top surface of the first oxide layer. CMP can be utilized to perform the planarization. Various methods and techniques can be utilized to remove the photoresist. For example, one can remove the photoresist utilizing a combination of a plasma resist strip followed by a SPM (sulfuric peroxide mix) or other chemical wet cleaning process to remove the remaining residue. In some examples, an etching process, including but not limited to, plasma etching, can be utilized to remove the photoresist. In some examples, after a chemical process is utilized, the remainder of the residue can be removed via etching.
Depending on the techniques used to form the germanium layer, the nature and shape of the layer can vary. In some examples, wherein the structure includes a conductive layer (e.g., metal, which will be described in greater detail herein) forming this germanium layer includes sputtering a conductive layer on the top surface of the first oxide layer. This example can also include depositing photoresist on a first portion of the conductive layer, wherein the second portion of the first oxide layer remains exposed (the photoresist does not cover this portion of the first oxide layer). Based on depositing the photoresist, one can remove a second portion of the conductive layer with etching (the photoresist is not deposited on the second portion of the conductive layer). This etching removes the top surface of the first oxide layer and the first portion of the conductive layer. After these structural changes are implemented, one can deposit a layer of silicon germanium on the top surface of the first oxide layer.
Another example that results in a germanium layer of a distinct configuration is a method where forming the germanium layer over a top surface of the sensor includes depositing photoresist on a first portion of the top surface of the first oxide layer. Based on depositing the photoresist, this example of the method includes etching through a second portion of the top surface of the first oxide layer (the photoresist is not deposited on the second portion of the top surface of the first oxide layer) to form one or more trenches in the first oxide layer. The method then includes depositing the germanium layer above the first oxide layer. This depositing action partially fills the one or more trenches in the first oxide layer rendering the one or more trenches shallower than prior to the depositing. The method then includes depositing a crosstalk mitigating substance (e.g., oxide, nitride, and silicon), above the germanium layer, wherein the depositing fills a remainder of the one or more trenches in the first oxide layer (the germanium did not fill the entirety of the trenches). The method then includes planarizing (e.g., utilizing CMP) the crosstalk mitigating substance such that the top surface of the germanium layer is a contiguous surface that includes a portion of the crosstalk mitigating substance and the first portion of the top surface of the first oxide layer.
Returning to
Continuing with the workflow 1500 of
The aspect in the methods described herein of forming the germanium layer on the top surface of the sensor (1610) can include various sub-aspects. In one example, the formation of this layer includes depositing silicon germanium on the top surface of the first oxide layer (this is the oxide layer that is part of the initial sensor). This example includes depositing a conductive layer on the top surface of the silicon germanium. One can also deposit a photoresist on a first portion of the conductive layer. The photoresist preserves the parts of the layer upon which it is deposited so one can etch through a second portion of the conductive layer, the portion upon which the photoresist is not deposited, to remove this second portion of the conductive layer. After this etching is complete, the top surface of the germanium layer includes the first portion of the conductive layer and a portion of the silicon germanium.
Another variation in forming the germanium layer involves depositing a conductive layer on the top surface of the sensor and depositing photoresist on a first portion of the conductive layer. After depositing the photoresist, one can etch through a second portion of the conductive layer (i.e., the portion of the layer upon which the photoresist is not deposited) and the etching removes the second portion of the conductive layer. Once the etching is complete, this example of the method proceeds to deposit silicon germanium over a portion of the first oxide layer and the first portion of the conductive layer.
Returning to
As with the workflow 1500 of
Additional aspects can be included in the workflow 1600. For example, one can form a silicon layer on the top surface of the second oxide layer. Additionally, some examples include depositing a conductive layer on the top surface of the second oxide layer. Upon depositing this layer one can deposit photoresist on a first portion of the conductive layer. After depositing the photoresist, one can etch through a second portion of the conductive layer (the photoresist is not deposited on the second portion of the conductive layer) to remove the second portion of the conductive layer.
Each workflow in
In each of the workflow 1803-1804 of
As discussed above, certain of the biosensors formed with the methods discussed herein include nanowells, which perform some of the desired functionality. Thus, the workflows 1802-1804 of
Returning to
Each workflow 2002, 2003, 2004 in
In the second and third workflow 2003-2004, the low index material 2030 in the lightpipe portion of the sensor is replaced first, by depositing a photoresist (e.g., utilizing photolithography) 2011 on a first portion of a top surface of the low index material (the portions that are not above the lightpipe) (2012), and then, by etching where the photoresist 2011 is not deposited to form trenches 2013 in the lightpipe 2030 areas, and then removing the photoresist (e.g., utilizing resist strips, chemical cleaning, and/or etching) (2014). One then fills the trenches 2013 with the material of choice (2015) (e.g., utilizing PECVD), in the second workflow 2003; this material is a material with a high refractive index 2062 (e.g., an oxide of nitride including but not limited to SiO), and in the third workflow 2004, this material is silicon 2063. After the trenches are filled with a material, the top of the material (e.g., a material with a high refractive index 2062 or silicon 2063) can be planarized (e.g., using CMP) (2016) and then, one can form the blocking layer 2077 (2008), deposit photoresist 2011 (2012), etch the blocking layer 2077 to leave blocking elements 2074 at the top surface of the sensor 2010, remove the photoresist, and deposit the germanium layer 2070 (2018). This germanium layer 2070 (e.g., SiGe) can be formed using a sputter technique. As discussed earlier, depending upon the desired topography of the resultant biosensor (e.g., its intended use), planarization of its surfaces, including the use of CMP, can be omitted.
In each of the workflow 2003-2004 of
As discussed above, certain of the biosensors formed with the methods discussed herein include nanowells, which perform some of the desired functionality. Thus, the workflows 2002-2004 of
Returning to
Each of the biosensors 2101a-2101b includes a germanium layer 2170 formed in the lightpipe 2130 on part of the remaining low (refractive) index layer 2160, after a portion of the low (refractive) index layer 2160 is removed (specifically, from the lightpipe 2130), a first conductive layer 2180 (e.g., metal) formed over a top surface of the sensor 2110, a second low (refractive) index layer (e.g., oxide) 2183 formed over a top surface of the first conductive layer 2180, and a second conductive layer 2190 (e.g., metal) formed over a top surface of the second low index layer 2183. In these examples, the second conductive layer 2190, the second low index layer 2183, and the first conductive layer 2180, include trenches 2173. These trenches 2173 can form nanowells 2176. Each trench (e.g., nanowell) is positioned above at least one diode of the diodes 2150 (i.e., on a vertical axis extending from a bottom surface of the sensor 2110 to the top surface of the second low index layer 2183). Each biosensor 2101a-2101b is topped with a passivation layer 2197, which in these examples, can be comprised of silicon.
Each workflow in
After planarizing the surface, (2221) (e.g., using CMP) fill the remainder of the trenches 2244 with either silicon 2261 or a material with a high refractive index 2269 (e.g., oxide and/or nitride) (2222) (e.g., utilizing CVD). The top surface of the resulting structure can then be planarized, e.g., utilizing CMP (2224). The planarized surface includes either silicon 2261 or a material with a high refractive index 2269, germanium 2270 (e.g., SiGe), and portion of the low index material in the low-index layer 2260. As discussed earlier, depending upon the desired topography of the resultant biosensor (e.g., its intended use), planarization of its surfaces, including the use of CMP, can be omitted.
One can form a first conductive layer 2280 (e.g., metal) over a top surface of the sensor 2210 (e.g., using a technique including but not limited to, metal sputtering) (2228). This example of the method can then include forming a second low index layer 2283 (e.g., an oxide layer) over a top surface of this first conductive layer 2280 (2238). Atop the second low index layer 2283, one can form a second conductive layer 2290 (2248).
As discussed above, certain of the biosensors formed with the methods discussed herein include nanowells, which perform some of the desired functionality. Thus, the workflows 2202-2203 of
Continuing with
Each of the biosensors 2301a-2301c includes an etched germanium layer 2370 formed over a top surface of the sensor 2310. The germanium layer 2370 is etched to include trenches 2379. A second low (refractive) index layer (e.g., oxide) 2383 is formed over a top surface of the germanium layer 2370. Parts of the second low (refractive) index layer (e.g., oxide) 2383 fill the trenches 2379 in the germanium layer. The first example 2301a includes a conductive layer 2387 (e.g., metal) formed over a top surface of the germanium layer 2370, including in the trenches 2379, situated between the germanium layer 2370 and the second low (refractive) index layer 2383. The third example 2301c includes a conductive layer 2387 (e.g., metal) formed on the top surface of the germanium layer 2370. In these examples, the second low index layer 2383 includes trenches 2373. These trenches 2373 can form nanowells 2376. Each trench (e.g., nanowell) is positioned above at least one diode of the diodes 2350 (i.e., on a vertical axis extending from a bottom surface of the sensor 2310 to the top surface of the second low index layer 2383). Each biosensor 2301a-2301c is topped with a passivation layer 2397, which in these examples, can be comprised of silicon.
In examples that include nanowells 2476, one can deposit photoresist 2411 on a first portion of a top surface of the second low index layer 2483 (2458) (e.g., using photolithography). Portions of the surfaces upon which photoresist 2411 is deposited are preserved during a subsequent etching process. In these examples, the photoresist 2411 is deposited on portions of the top surface of the second low index layer 2483 above (on a longitudinal axis) the trenches 2479 in the germanium layer 2470. One can then etch the portions of the second low index layer 2483 that are not covered by the photoresist 2411 (e.g., utilizing an oxide and metal etching process) to form trenches 2473 in the second low index layer 2483, exposing parts of the germanium layer 2470 (2468). One can also remove the photoresist 2411. In some examples, various chemistries can then be applied to the trenches 2473. A passivation layer 2497 can be deposited atop the top surface of the structure, which can be a silicon layer (2478).
In the third workflow 2404, before depositing the passivation layer 2497 (2478), one deposits a conductive layer 2487 on the second low index layer 2483 (which is already etched) (2481). This workflow 2404 includes covering a first portion of the conductive layer 2487 with a photoresist 2411 (2482). Where the photoresist is not covering the conductive layer 2487, one removes the conductive layer 2487 (e.g., using etching), and removes the photoresist (2484). Then, a passivation layer 2497 can be deposited atop the top surface of the structure, which can be a silicon layer (2478).
Upon forming the blocking (conductive) elements 2674, these workflows 2602-2604 proceed similarly in the workflows 2402-2404 of
In the first workflow 2602, one can form a conductive layer 2687 (e.g., metal) over a top surface of the germanium layer 2670 (e.g., using a technique including but not limited to, metal sputtering) (2628). In some examples, one removes certain portions of the conductive layer 2687 (the portions that do not line the trenches 2679), by depositing a photoresist 2611 on the top surface of the structure in the trenches 2679 (2629) and etching the exposed portions of the conductive layer 2687 (2631), exposing portions of the germanium layer 2670. After forming the conductive layer 2687 (e.g., via a metal sputter) in the first workflow 2602 and without forming this layer in the second and third workflows 2603-2604, one can form a second low index layer 2683 (e.g., an oxide layer) over a top surface of the germanium later 2670 (which includes filling the trenches 2679 in the germanium layer 2670), and this top surface, in the first workflow 2602, includes the conductive layer 2687.
In examples that include nanowells 2676, one can deposit photoresist 2611 on a first portion of a top surface of the second low index layer 2683 (2658) (e.g., using photolithography). Portions of the surfaces upon which photoresist 2611 is deposited are preserved during a subsequent etching process. In these examples, the photoresist 2611 is deposited on portions of the top surface of the second low index layer 2683 above (on a longitudinal axis) the trenches 2679 in the germanium layer 2670. One can then etch the portions of the second low index layer 2683 that are not covered by the photoresist 2611 (e.g., utilizing an oxide and metal etching process) to form trenches 2673 in the second low index layer 2683, exposing parts of the germanium layer 2670 (2668). One can then remove the photoresist 2611. In some examples, various chemistries can then be applied to the trenches 2673. A passivation layer 2697 can be deposited atop the top surface of the structure, which can be a silicon layer (2678).
In the third workflow 2604, before depositing the passivation layer 2697 (2678), one deposits a conductive layer 2687 on the second low index layer 2683 (which is already etched) (2681). This workflow 2604 includes covering a first portion of the conductive layer 2687 with a photoresist 2611 (2682). Where the photoresist is not covering the conductive layer 2687, one removes the conductive layer 2687 (e.g., using etching), as well as the photoresist 2611 (following completion of the etching). Then, a passivation layer 2697 can be deposited atop the top surface of the structure, which can be a silicon layer (2678).
Turning to
In
Each workflow in
Picking up the second workflow 2803 after forming the blocking elements 2874 and the first workflow 2802 at the beginning, one forms a germanium layer 2870 over a top surface of the sensor 2810 (which includes the blocking elements 2874 in the second workflow 2803) (2818). This germanium layer 2870 (e.g., SiGe) can be formed using a sputter technique. Once the germanium layer 2870 has been deposited (2818), one can form a first conductive layer 2880 (e.g., metal) over a top surface of the germanium layer 2870 (e.g., using a technique including but not limited to, metal sputtering) (2828). One can then form a second low index layer 2883 (e.g., an oxide layer) over a top surface of this first conductive layer 2880 (2838). Atop the second low index layer 2883, one can form a second conductive layer 2890 (2848).
Forming nanowells is optional (as discussed herein) and some examples will omit them, but for illustrative purposes, portions of this aspect are included in
The biosensors 2901a-2901c in
The workflows 3002-3004 all include forming a conductive (e.g., metal) layer 3077 atop the sensor 3010. This layer is a blocking layer that contributes to crosstalk reduction. Generally,
Upon forming the blocking (conductive) elements 3074, these workflows 3002-3004 proceed similarly in the workflows 2402-2404 of
In the first workflow 3002, one can form a conductive layer 3087 (e.g., metal) over a top surface of the germanium layer 3070 (e.g., using a technique including but not limited to, metal sputtering) (3028). In some examples, one removes certain portions of the conductive layer 3087 (the portions that do not line the trenches 3079), by depositing a photoresist 3011 on the top surface of the structure in the trenches 3079 (3029) and etching the exposed portions of the conductive layer 3087 (3031), exposing portions of the germanium layer 3070. After forming the conductive layer 3087 (e.g., via a metal sputter) in the first workflow 3002 and without forming this layer in the second and third workflows 3003-3004, one can form a second low index layer 3083 (e.g., an oxide layer) over a top surface of the germanium layer 3070 (which includes filling the trenches 3079 in the germanium layer 3070), and this top surface, in the first workflow 3002, includes the conductive layer 3087.
In examples that include nanowells 3076, one can deposit photoresist 3011 on a first portion of a top surface of the second low index layer 3083 (3058) (e.g., using photolithography). Portions of the surfaces upon which photoresist 3011 is deposited are preserved during a subsequent etching process. In these examples, the photoresist 3011 is deposited on portions of the top surface of the second low index layer 3083 above (on a longitudinal axis) the trenches 3079 in the germanium layer 3070. One can then etch the portions of the second low index layer 3083 that are not covered by the photoresist 3011 (e.g., utilizing an oxide and metal etching process) to form trenches 3073 in the second low index layer 3083, exposing parts of the germanium layer 3070 (3068). One can then remove the remaining photoresist 3011. In some examples, various chemistries can then be applied to the trenches 3073. A passivation layer 3097 can be deposited atop the top surface of the structure, which can be a silicon layer (3078).
In the third workflow 3004, before depositing the passivation layer 3097 (3078), one deposits a conductive layer 3087 on the second low index layer 3083 (which is already etched) (3081). This workflow 3004 includes covering a first portion of the conductive layer 3087 with a photoresist 3011 (3082). Where the photoresist is not covering the conductive layer 3087, one removes the conductive layer 3087 (e.g., using etching) and then removes the photoresist 3011 (e.g., utilizing resist strips, chemical cleaning, and/or etching). Then, a passivation layer 3097 can be deposited atop the top surface of the structure, which can be a silicon layer (3078).
Each apparatus described herein can be utilized as a biosensor.
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.
In some examples herein, the method comprises: forming one or more diodes on a first surface of a substrate, wherein the first surface of the substrate is parallel to a second surface of the substrate; forming one or more trenches between the one or more diodes, the one or more trenches extending toward the second surface of the substrate from the first surface of the substrate, wherein the forming comprises filling the one or more trenches and planarizing the one or more filled trenches to form a first surface substantially parallel to a first surface of the one or more diodes and the first surface of the substrate; removing a portion of the substrate such that the one or more trenches extend through the substrate from the first surface of the substrate to the second surface of the substrate; bonding a carrier wafer to the second surface of the substrate; forming a germanium layer above the second surface of the substrate; and forming a dielectric stack above a surface of the germanium layer.
In some examples of the method, forming the one or more trenches comprises etching the one or more trenches in the substrate.
In some examples of the method, the substrate comprises silicon.
In some examples of the method, filling the one or more trenches comprises filling the one or more trenches with one or more dielectric layers.
In some examples of the method, the dielectric stack comprises one or more nanowells.
In some examples of the method, forming the germanium layer on the second surface of the substrate comprises depositing germanium on the second surface of the substrate.
In some examples of the method, a technique for the depositing is selected from the group consisting of: Plasma Enhanced Chemical Vapor Deposition (PECVD), sputter, e-beam evaporation, crystalline growth and etching, and radical activation bonding in vacuum.
In some examples of the method, the selected technique is crystalline growth and etching and the crystalline growth and etching comprises one of: transfer wafer bonding or direct wafer bonding.
In some examples of the method, forming the germanium layer above the second surface of the substrate further comprises: forming a first one or more dielectric layers on the second surface of the substrate; forming the germanium layer on a surface of the one or more dielectric layers; and forming a second one or more dielectric layers on a surface of the germanium layer.
In some examples of the method, the substrate, one or more diodes, the carrier wafer, and the one or more filled trenches comprise a sensor.
In some examples of the method, the sensor comprises a complementary metal-oxide-semiconductor (CMOS).
In some examples of the method, the germanium layer comprises germanium and silicon.
In some examples of the method, the stack comprises: one or more dielectric layers; and a sensor compatible metal.
In some examples of the method, the germanium layer performs loss induced crosstalk reduction and filters out excitation light when light source emits light toward the dielectric stack.
In some examples of the method, based on the loss induced crosstalk reduction, a signal at neighboring pixels is substantially lower than a signal at paired pixels.
In some examples herein, the method comprises: forming a germanium layer above a top surface of an image sensor; and forming a dielectric stack above a top surface of the germanium layer.
In some examples of the method, the dielectric stack comprises one or more nanowells.
In some examples of the method, forming the germanium layer above the top surface of the image sensor further comprises: forming a first one or more dielectric layers on the top surface of the image sensor; forming the germanium layer on a surface of the one or more dielectric layers; and forming a second one or more dielectric layers on a surface of the germanium layer.
In some examples of the method, forming the germanium layer above the top surface of the image sensor comprises depositing germanium above the top surface of the image sensor.
In some examples of the method, a technique for the depositing is selected from the group consisting of: Plasma Enhanced Chemical Vapor Deposition (PECVD), sputter, e-beam evaporation, crystalline growth and etching, and radical activation bonding in vacuum.
In some examples of the method, the selected technique is crystalline growth and etching and the crystalline growth and etching comprises one of: transfer wafer bonding or direct wafer bonding.
In some examples of the method, the image sensor comprises a complementary metal-oxide-semiconductor (CMOS).
In some examples of the method, the image sensor comprises a backside image sensor with one or more deep trenches.
In some examples of the method, the germanium layer performs loss induced crosstalk reduction and filters out excitation light when light source emits light toward the dielectric stack.
In some examples herein, the method comprises: obtaining a biosensor, the biosensor comprising: a germanium layer above a top surface of an image sensor; and a dielectric stack above a top surface of the germanium layer, wherein the dielectric stack comprises wells and reaction sites; placing one or more nucleic acids in the reaction sites; and exposing the reaction sites of the biosensor to light from a light source, wherein the light comprises excitation light and emitted light; obtaining, by the image sensor, the emitted light, from the reaction sites, via the germanium layer, the emitted light, wherein the germanium layer filters the excitation light from the light and reduces crosstalk associated with the emitted light; and identifying, by the image sensor, based on the emitted light, a composition of the nucleic acids.
In some examples of the method, the image sensor comprises one or more diodes.
In some examples of the method, the obtaining the emitted light, from the reaction sites, via the germanium layer further comprises: propagating the emitted light through the germanium layer at non-vertical angles to reach at least one diode of the one or more diodes.
In some examples of the method, the reaction sites comprise fluorophores, and wherein based on exposing the reaction sites of the biosensor to light from a light source, the excitation light causes the fluorophores to emit the emitted light.
In some examples of the method, the germanium layer comprises germanium and silicon.
In some examples of the method, the biosensor further comprises: a first one or more dielectric layers on the top surface of the image sensor; and a second one or more dielectric layers on a surface of the germanium layer.
In some examples of the method, the image sensor comprises a complementary metal-oxide-semiconductor (CMOS).
In some examples of the method, the germanium layer comprises germanium and silicon.
In some examples of the method, the dielectric stack comprises: one or more dielectric layers; and a sensor compatible metal.
In some examples herein, the apparatus comprises: a filter layer comprising germanium; a flow channel floor defining a plurality of wells, wherein each well provides a reaction site, wherein the filter layer is positioned under flow channel floor, wherein the filter layer spans contiguously under the plurality of wells.
In some examples, of the apparatus, the apparatus further comprises: a plurality of sensors positioned under the filter layer, each sensor of the plurality of sensors centered under a corresponding well and reaction site, such that each sensor forms a sensing pair with a corresponding reaction site.
In some examples, of the apparatus, the filter layer further comprises silicon.
In some examples, of the apparatus, the filter layer has a height of approximately 300 micrometers to approximately 500 micrometers.
In some examples herein, a method for utilizing a biosensor (e.g., an apparatus) comprises: placing one or more nucleic acids in reaction sites of an apparatus, the apparatus comprising: a filter layer comprising germanium; a flow channel floor defining a plurality of wells, wherein each well provides a reaction site of the reaction sites, wherein the filter layer is positioned under flow channel floor; wherein the filter layer spans contiguously under the plurality of wells; exposing the reaction sites of the apparatus to light from a light source, wherein the light comprises excitation light and emitted light; receiving the emitted light from the reaction sites via the filter layer, wherein the filter layer filters the excitation light from the light and reduces crosstalk associated with the emitted light; and identifying, based on the emitted light, a composition of the one or more nucleic acids.
In some examples of the method, the apparatus includes a plurality of sensors positioned under the filter layer, each sensor of the plurality of sensors centered under a corresponding well and another reaction site of the reaction sites, such that each sensor forms a sensing pair with a corresponding reaction site.
In some examples of the method, the filter layer of the apparatus further comprises silicon.
In some examples of the method, the filter layer has a height of approximately 300 micrometers to approximately 500 micrometers.
In some examples herein, a method for forming aspects of a biosensor comprises: forming a germanium layer over a top surface of a sensor, wherein the sensor comprises: a substrate comprising one or more diodes; a first oxide layer formed over a top surface of the substrate; forming a first conductive layer over a top surface of the germanium layer; forming a second oxide layer over a top surface of the first conductive layer; forming a second conductive layer over a top surface of the second oxide layer; depositing photoresist on a first portion of a top surface of the second conductive layer; and etching through a second portion of the top surface of the second conductive layer, wherein the photoresist is not deposited on the second portion of the top surface of the second conductive layer, a portion of the second oxide layer, and a portion of the first conductive layer, wherein the etching forms one or more trenches, wherein the one or more trenches are each positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the second oxide layer.
In some examples of the method, the germanium layer further comprises silicon, and forming the germanium layer comprises sputtering silicon-germanium onto the top surface of the first oxide layer.
In some examples of the method, the one or more trenches comprise nanowells.
In some examples of the method, forming the germanium layer over a top surface of a sensor further comprises: depositing photoresist on a first portion of the top surface of the first oxide layer; etching through a second portion of the top surface of the first oxide layer, wherein the photoresist is not deposited on the second portion of the top surface of the first oxide layer, wherein the etching forms one or more trenches in the first oxide layer; depositing a crosstalk mitigating substance above the first oxide layer, wherein the depositing fills the one or more trenches in the first oxide layer; planarizing the crosstalk mitigating substance such that a portion of the crosstalk mitigating substance forms a contiguous surface with the first portion of the top surface of the first oxide layer; and depositing a layer of silicon germanium on the top surface of the first oxide layer.
In some examples of the method, the crosstalk mitigating substance is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the method, the method also includes: forming a passivation layer over the first portion of the top surface of the second conductive layer.
In some examples of the method, forming the germanium layer over a top surface of a sensor further comprises: sputtering an additional conductive layer on the top surface of the first oxide layer; depositing photoresist on a first portion of the additional conductive layer, wherein the second portion of the first oxide layer is exposed; removing a second portion of the additional conductive layer with etching, wherein the photoresist is not deposited on the second portion of the additional conductive layer, wherein based on the removing, the top surface of the first oxide layer and the first portion of the additional conductive layer are exposed; and depositing a layer of silicon germanium on the top surface of the first oxide layer.
In some examples of the method, forming the germanium layer over a top surface of the sensor comprises: depositing photoresist on a first portion of the top surface of the first oxide layer; etching through a second portion of the top surface of the first oxide layer, wherein the photoresist is not deposited on the second portion of the top surface of the first oxide layer, wherein the etching forms one or more trenches in the first oxide layer; depositing the germanium layer above the first oxide layer, wherein the depositing partially fills the one or more trenches in the first oxide layer; depositing a crosstalk mitigating substance above the germanium layer, wherein the depositing fills a remainder of the one or more trenches in the first oxide layer; and planarizing the crosstalk mitigating substance such that the top surface of the germanium layer is a contiguous surface comprising a portion of the crosstalk mitigating substance and the first portion of the top surface of the first oxide layer.
In some examples of the method, the crosstalk mitigating substance is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the method, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the method includes: forming a silicon layer on the top surface of the second oxide layer.
In some examples of the method, the first conductive layer and the second conductive layer are comprised of metal.
In some examples of the method, the first oxide layer comprises electrically conductive materials.
In some examples of the method, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples herein, a method for forming aspects of a biosensor comprises: forming a germanium layer over a top surface of a sensor, wherein the sensor comprises: a substrate comprising one or more diodes; a first oxide layer formed over a top surface of the substrate, wherein forming the germanium layer comprises: depositing photoresist on a first portion of a top surface of the germanium layer; and etching through a second portion of the top surface of the germanium layer, wherein the photoresist is not deposited on the second portion of the top surface of the germanium, wherein the etching forms one or more trenches, wherein the trenches are each positioned above a space between at least one diode and another diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the germanium layer; forming a second oxide layer over a top surface of the germanium layer; depositing photoresist on a first portion of a top surface of the second oxide layer; and etching through a second portion of the top surface of the second oxide layer, wherein the photoresist is not deposited on the second portion of the top surface of the second oxide layer, wherein the etching forms an additional one or more trenches, wherein the additional one or more trenches are each positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the second oxide layer.
In some examples of the method, the method includes: forming a silicon layer over the top surface of the second oxide layer.
In some examples of the method, forming the germanium layer over the top surface of the sensor further comprises: depositing silicon germanium on the top surface of the first oxide layer; depositing a conductive layer on the silicon germanium; and depositing photoresist on a first portion of the conductive layer; and etching through a second portion of the conductive layer, wherein the photoresist is not deposited on the second portion of the conductive layer, wherein the etching removes the second portion of the conductive layer, and wherein the top surface germanium layer comprises a surface comprising a portion of the silicon germanium and the first portion of the conductive layer.
In some examples of the method, the method includes: depositing a conductive layer on the top surface of the second oxide layer; depositing photoresist on a first portion of the conductive layer; and etching through a second portion of the conductive layer, wherein the photoresist is not deposited on the second portion of the conductive layer, wherein the etching removes the second portion of the conductive layer.
In some examples of the method, forming the germanium layer over the top surface of the sensor further comprises: depositing silicon germanium on the top surface of the first oxide layer; depositing a conductive layer on the top surface of the silicon germanium; depositing photoresist on a first portion of the conductive layer; and etching through a second portion of the conductive layer, wherein the photoresist is not deposited on the second portion of the conductive layer, wherein the etching removes the second portion of the conductive layer, and where the top surface of the germanium layer comprises the first portion of the conductive layer and a portion of the silicon germanium.
In some examples of the method, forming the germanium layer over the top surface of the sensor further comprises: depositing a conductive layer on the top surface of the sensor; depositing photoresist on a first portion of the conductive layer; and etching through a second portion of the conductive layer, wherein the photoresist is not deposited on the second portion of the conductive layer, wherein the etching removes the second portion of the conductive layer; and depositing silicon germanium over a portion of the first oxide layer and the first portion of the conductive layer.
In some examples of the method, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the first oxide layer comprises conductive components.
In some examples herein, an apparatus including a biosensor comprises: a sensor comprising: a substrate comprising one or more diodes; a first oxide layer formed over a top surface of the substrate; a germanium layer formed over a top surface of the sensor; a first conductive layer formed over a top surface of the germanium layer; a second oxide layer formed over a top surface of the first conductive layer; a second conductive layer formed over a top surface of the second oxide layer, wherein the second conductive layer, the second oxide layer, and the first conductive layer comprise one or more trenches, and wherein the one or more trenches are each positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the second oxide layer.
In some examples of the apparatus, the germanium layer further comprises silicon.
In some examples of the apparatus, the one or more trenches comprise nanowells.
In some examples of the apparatus, the first oxide layer comprises an oxide substance and a crosstalk mitigating substance, wherein the crosstalk mitigating substance fills trench structures in the oxide substance.
In some examples of the apparatus, the crosstalk mitigating substance is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the apparatus, the apparatus includes: a passivation layer formed over the first portion of the top surface of the second conductive layer.
In some examples of the apparatus, the germanium layer comprises: an additional conductive layer over the top surface of the first oxide layer, wherein the additional and conductive layer comprises fissures; and a layer of silicon germanium over the top surface of the first oxide layer.
In some examples of the apparatus, the first oxide layer comprises trench structures, wherein the top surface of the sensor is an uneven surface and the germanium layer formed over a top surface of the sensor comprises: silicon germanium filling a portion of the trench structures; and a crosstalk mitigating substance filling a remainder of the trench structures, wherein the top surface of the germanium layer is a contiguous surface comprising a portion of the crosstalk mitigating substance and a portion of a top surface of the first oxide layer.
In some examples of the apparatus, the crosstalk mitigating substance filling the remainder of the trench structures is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the apparatus, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the apparatus, the oxide layer comprises electrically conductive materials.
In some examples of the apparatus, the apparatus includes: a silicon layer on the top surface of the second oxide layer.
In some examples of the apparatus, the first conductive layer and the second conductive layer are comprised of metal.
In some examples of the apparatus, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the apparatus, the apparatus includes a pixel pitch of less than one micron.
In some examples of the apparatus, the germanium layer is of a thickness of less than 400 nm.
In some examples of the apparatus, the germanium layer is of a thickness between approximately 300 nm and approximately 330 nm.
In some examples herein, an apparatus including a biosensor comprises: a sensor comprising: a substrate comprising one or more diodes; and a first oxide layer formed over a top surface of the substrate; a germanium layer over a top surface of a sensor, wherein the germanium layer comprises one or more trenches positioned above a space between at least one diode and another diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the germanium layer; and a second oxide layer over a top surface of the germanium layer, wherein the second oxide layer fills the trenches in the germanium layer, wherein the second oxide layer comprises one or more trenches, each trench in the second oxide layer positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to a top surface of the second oxide layer, wherein the trenches in the second oxide layer expose portions of the germanium layer.
In some examples of the apparatus, the apparatus includes: a silicon layer over the top surface of the second oxide layer.
In some examples of the apparatus, the apparatus includes: a conductive layer comprising lining the one or more trenches in the germanium layer.
In some examples of the apparatus, the apparatus includes: a conductive layer over the top surface of the second oxide layer.
In some examples of the apparatus, the apparatus includes: a conductive layer over the top surface of the sensor.
In some examples of the apparatus, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the apparatus, the first oxide layer comprises conductive components.
In some examples of the apparatus, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the apparatus, the apparatus includes: a pixel pitch of less than one micron.
In some examples of the apparatus, the germanium layer is of a thickness of less than 400 nm.
In some examples of the apparatus, the germanium layer is of a thickness of less than 300 nm.
In some examples of the apparatus, the germanium layer is of a thickness between approximately 300 nm and approximately 330 nm.
In some examples herein, a method for utilizing a biosensor comprises: placing one or more nucleic acids in reaction sites of a sensor, the sensor comprising: a substrate comprising one or more diodes; and a first oxide layer formed over a top surface of the substrate; a germanium layer over a top surface of the first oxide layer, wherein the germanium layer comprises one or more trenches positioned above a space between at least one diode and another diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the germanium layer; and a second oxide layer over a top surface of the germanium layer, wherein the second oxide layer fills the trenches in the germanium layer, wherein the second oxide layer comprises one or more trenches, each trench in the second oxide layer positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to a top surface of the second oxide layer, wherein the trenches in the second oxide layer expose portions of the germanium layer, wherein the second oxide layer comprises wells and the reaction sites; exposing the reaction sites of the sensor to light from a light source, wherein the light comprises excitation light and emitted light; receiving, by the one or more diodes, the emitted light from the reaction sites via the germanium layer, wherein the germanium layer filters the excitation light from the light and reduces crosstalk associated with the emitted light; and identifying, based on the emitted light, a composition of the nucleic acids.
In some examples of the method, the sensor further comprises: a conductive layer on the top surface of the sensor.
In some examples of the method, receiving the emitted light from the reaction sites via the germanium layer further comprises: propagating the emitted light through the germanium layer to reach at least one diode of the one or more diodes.
In some examples of the method, the reaction sites comprise fluorophores, and wherein based on exposing the reaction sites of the sensor to light from a light source, the excitation light causes the fluorophores to emit the emitted light.
In some examples of the method, the germanium layer comprises germanium and silicon.
In some examples of the method, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the sensor further comprises: a silicon layer over the top surface of the second oxide layer.
In some examples of the method, the sensor further comprises: a conductive layer comprising lining the one or more trenches in the germanium layer.
In some examples of the method, the sensor further comprises: a conductive layer over the top surface of the second oxide layer.
In some examples herein, a method of utilizing a biosensor comprises: placing one or more nucleic acids in reaction sites of a biosensor, the biosensor comprising: a sensor, the sensor comprising: a substrate comprising one or more diodes; and a first oxide layer formed over a top surface of the substrate; a germanium layer formed over a top surface of the sensor; a first conductive layer formed over a top surface of the germanium layer; a second oxide layer formed over a top surface of the first conductive layer; a second conductive layer formed over a top surface of the second oxide layer, wherein the second conductive layer, the second oxide layer, and the first conductive layer comprise one or more trenches, and wherein the one or more trenches are each positioned above at least one diode of the one or more diodes, on a vertical axis extending from a bottom surface of the sensor to the top surface of the second oxide layer, wherein the trenches comprise wells and reaction sites; exposing the reaction sites of the biosensor to light from a light source, wherein the light comprises excitation light; receiving, by the one or more diodes, the emitted light from the reaction sites via the germanium layer, wherein the germanium layer filters the excitation light and reduces crosstalk associated with the emitted light; and identifying, based on the emitted light, a composition of the one or more nucleic acids.
In some examples of the method, the germanium layer further comprises silicon.
In some examples of the method, the first oxide layer comprises an oxide substance and a crosstalk mitigating substance, and the crosstalk mitigating substance fills trench structures in the oxide substance.
In some examples of the method, the crosstalk mitigating substance is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the method, the biosensor further comprises: a passivation layer formed over the first portion of the top surface of the second conductive layer.
In some examples of the method, the germanium layer comprises: an additional conductive layer over the top surface of the first oxide layer, wherein the additional and conductive layer comprises fissures; and a layer of silicon germanium over the top surface of the first oxide layer.
In some examples of the method, the first oxide layer comprises trench structures, wherein the top surface of the sensor is an uneven surface and the germanium layer formed on a top surface of the sensor comprises: silicon germanium filling a portion of the trench structures; and a crosstalk mitigating substance filling a remainder of the trench structures, wherein the top surface of the germanium layer is a contiguous surface comprising a portion of the crosstalk mitigating substance and a portion of a top surface of the first oxide layer.
In some examples of the method, the crosstalk mitigating substance filling the remainder of the trench structures is selected from the group consisting of: oxide, nitride, and silicon.
In some examples of the method, the sensor is a front-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the oxide layer comprises electrically conductive materials.
In some examples of the method, the sensor is a back-side illuminated complementary metal-oxide semiconductor.
In some examples of the method, the obtaining the emitted light, from the reaction sites, via the germanium layer further comprises: propagating the emitted light through the germanium layer to reach at least one diode of the one or more diodes.
In some examples of the method, the reaction sites comprise fluorophores, and wherein based on exposing the reaction sites of the sensor to light from a light source, the excitation light causes the fluorophores to emit the emitted light.
The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various examples of the present implementation. In this regard, each block in the flowchart or block diagrams can represent a module, segment, or portion of instructions, which comprises one or more executable instructions for implementing the specified logical function(s). In some alternative implementations, the functions noted in the blocks can occur out of the order noted in the Figures. For example, two blocks shown in succession can, in fact, be executed substantially concurrently, or the blocks can sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts or carry out combinations of special purpose hardware and computer instructions.
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.
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.
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.
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 those skilled 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.
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 art 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.
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 such disclosed 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.
This application claims priority to U.S. Provisional Patent Application No. 63/362,909, which was filed on Apr. 13, 2022, and to U.S. Provisional Patent Application No. 63/485,400, which was filed on Feb. 16, 2023, which are both incorporated by reference herein in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63362909 | Apr 2022 | US | |
| 63485400 | Feb 2023 | US |
