WO2024259203A1

WO2024259203A1 - Sensor fanout packaging

Info

Publication number: WO2024259203A1
Application number: PCT/US2024/033967
Authority: WO
Inventors: Ravi Billa; Tracy FUNG; Hai Tran
Original assignee: Illumina Inc
Current assignee: Illumina Inc
Priority date: 2023-06-16
Filing date: 2024-06-14
Publication date: 2024-12-19
Anticipated expiration: 2025-12-16

Abstract

Provided herein include various examples of a method for manufacturing aspects of a flow cell. The method may include bonding a die to a first carrier with a first bonding material, encapsulating the die with a molding material, bonding a second carrier to a surface of the molding material with a second bonding material, releasing the first carrier from the die encapsulated with the molding material to expose a surface that includes fanout regions, applying chemistry to the exposed surface of the die such that the given surface of the die becomes an active detection area for the flow cell, and placing a lidding layer over the exposed surface to form a space over the active detection area; the space defines a fluidic channel.

Description

SENSOR FANOUT PACKAGING

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This PCT International Patent Application claims priority to U.S. Provisional Patent Application No. 63/508,708, filed June 16, 2023, entitled Sensor Fanout Packaging, the entire contents of which are hereby incorporated herein by reference.

BACKGROUND

[0002] 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.

[0003] In some conventional fluorescent-detection protocols, an optical system is used to direct an excitation light onto fluorescently labeled analytes and to also detect the fluorescent signals that may emit from the 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.

[0004] In flow cells, a fluidic channel is utilized to position matter above an active detection area of a detector (e.g, CMOS). The shape of the fluidic channel can impact the sequencing results and thus, manufacturing methods utilized to manufacture flow cells aim to create a flow cell with a predictable channel that delivers matter that is to be sequenced to an active detection area of a flow cell. A flow of sequencing reagents (fluids) over an active detection area may be improved when an entirety of a fluidic channel is flat and a top surface of a package encapsulating a sensor is contiguous with the top surface of the sensor.

SUMMARY

[0005] To position sequencing reagents (fluids) over an active detection area, the fluidic channel includes not only the active detection area, but also includes areas that do not participate in the detection. The fluid passes over these areas both before and after passing over the active detection area. Sacrificing part of a detector, which can be a complementary metal-oxide semiconductor (CMOS) die, to create these non-active areas is expensive and thus, various materials have been proposed to extend a surface in place of wasting space on a detector or sensor. Accordingly, in some flow cells, non-active areas, referred to as fanout areas or fanout surfaces, are built around a detector and extend the fluidic channel beyond the active detection area of a detector (e.g, CMOS). Some examples create fanout areas with an EMC package. An important challenge in forming these fluidic channels, which is addressed in the examples herein, is creating a flat surface, which includes both the fanout areas and the detectors (the detector includes the active detection area) because a warped fluidic channel can adversely affect detection (e.g., sequencing) results, including interfering with the ability of a flow cell to produce reproduceable results over time. Accordingly, it is beneficial to utilize both a flat fluidic fanout area with minimal step height at the detector (e.g., CMOS) to molding material (e.g., EMC) interface at the sidewall so as not to disturb the reagent flow and workflows that yield warpage- free molding material molded panels, thus minimizing or eliminating the wafer handleability concerns for downstream processing. To achieve both advantages, the examples herein include workflows that involve supporting a detector package that includes a molding material (e.g, an EMC wafer) with at least one support substrate.

[0006] 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 a flow cell. 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 i neon si stent), overcome these shortcomings. In some examples herein, the method comprises: bonding a die to a first carrier with a first bonding material, wherein a surface of the first carrier bonded to a given surface of die comprises a larger surface area than the given surface of the die, wherein the first bonding material covers the surface of the first carrier, wherein the given surface of the die comprises one or more reaction sites and one or more electrical contact points; encapsulating the die with a molding material, wherein portions of the molding material are flush to portions of the first bonding material; bonding a second carrier to a surface of the molding material with a second bonding material, wherein the surface of the first carrier and the surface of the molding material are parallel; releasing the first carrier from the die encapsulated with the molding material to expose a surface comprising the given surface of the die and the portions of the molding material, wherein the portions of the molding material comprise fanout regions; applying chemistry to the given surface of the die such that the given surface of the die becomes an active detection area; and placing a lidding layer over the surface comprising the given surface of the die and the portions of the molding material to form a space over the active detection area, wherein the space defines a fluidic channel.

[0007] In some examples, the method further comprises: releasing the second carrier from the surface of the molding material, orienting the die on the substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, where the substrate comprises electrical contact, and connecting the electrical contacts of the substrate to the electrical contact points of the die.

[0008] In some examples, the method further comprises: orienting the die on the substrate such that the second carrier is adjacent to an upper surface of the substrate, where the substrate comprises electrical contacts, and connecting the electrical contacts of the substrate to the electrical contact points of the die.

[0009] In some examples, the die comprises a complementary metal -oxide semiconductor (CMOS).

[0010] In some examples, the first carrier and the second carrier are each comprised of a material selected from the group consisting of: glass, quartz, silica, silicon, aluminum, and stainless steel. [0011] In some examples, the method further comprises: prior to bonding the second carrier to a surface of the molding material with a second bonding material, planarizing the surface of the molding material.

[0012] In some examples, releasing the first carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

[0013] In some examples, releasing the second carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

[0014] In some examples, the first carrier is transparent and releasing the first carrier comprises applying heat or applying ultraviolet radiation to the first carrier.

[0015] In some examples, the first carrier is not transparent and releasing the first carrier comprises applying heat to the first carrier.

[0016] In some examples, the first carrier and the second carrier are transparent, releasing the first carrier and releasing the second carrier comprise applying UV radiation to the first carrier and to the second carrier, and a wavelength of UV radiation applied to release the first carrier is different than a wavelength of ultraviolet radiation applied to release the second carrier.

[0017] In some examples, releasing the first carrier comprises applying thermal energy to the first carrier, releasing the second carrier comprises applying thermal energy to the second carrier, and a temperature of the thermal energy applied for releasing the second carrier is greater than or equal to a temperature of the thermal energy applied for releasing the first carrier.

[0018] In some examples, the surface of the first carrier and the given surface of the die are planar surfaces.

[0019] In some examples, the molding material comprises epoxy mold compound.

[0020] In some examples, bonding a die to a first carrier with a first bonding material comprises: prior to the bonding, simulating the die into portions, where each portion of the die comprises at least one reaction site of the one or more reaction sites, and orienting the portions of the die on the first bonding material at a lateral distance from each other. [0021] In some examples, placing the lidding layer over the surface comprises forming a stack and the method further comprises: modifying the stack by releasing the second carrier from the surface of the molding material; singulating the modified stack into packages, wherein each package comprises a given portion of the portions of the die; orienting at least one package on a substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the given portion of the die.

[0022] In some examples, placing the lidding layer over the surface comprises forming a stack and the method further comprises: singulating the stack into packages, wherein each package comprises a given portion of the portions of the die; orienting at least one package on a substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the given portion of the die.

[0023] 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 flow cells. 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 die packages, comprising: depositing a first bonding material on a planar surface of a first carrier; bonding two or more dies to the first carrier, the bonding comprising orienting the two or more dies on the first bonding material such that the first bonding material bonds the two or more dies to the first carrier, wherein the orienting comprises placing the two or more dies on the planar surface at orientations wherein each die of the two or more dies is at a lateral distance from a next die of the two or more dies, wherein each die comprises one or more nanowells and one or more electrical contact points, wherein the nanowells are coupled to the first bonding material; encapsulating the two or more dies with a molding material, wherein portions of the molding material are flush to portions of the first bonding material; bonding a second carrier to a surface of the molding material with a second bonding material, wherein the planar surface of the first carrier and the surface of the molding material are parallel and separated by a longitudinal distance; releasing the first carrier from the die encapsulated with the molding material to expose surfaces of the two or more dies comprising the nanowells and the portions of the molding material; and applying chemistry to surfaces of the two or more dies comprising the nanowells such that the surfaces of the two or more dies comprising the nanowells become active detection areas.

[0024] In some examples, forming the die packages further comprises: releasing the second carrier from the surface of the molding material; and dicing through the molding material to separate the two or more dies into individual die packages, wherein each die package comprises a die of the two or more dies and part of portions of the molding material comprising fanout regions on each side of the die of the two or more dies, wherein a top surface of each die package comprises an active detection areas of the active detection areas.

[0025] In some examples, the method further comprises: dicing through the molding material and the second carrier to separate the two or more dies into individual die packages, wherein each die package comprises a die of the two or more dies and part of portions of the molding material comprising fanout regions on each side of the die of the two or more dies, wherein a top surface of each die package comprises an active detection areas of the active detection areas.

[0026] In some examples, the method further comprises: orienting an individual die package of the individual die packages on a substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the individual die package.

[0027] In some examples, the method further comprises: singulating a die wafer to form the two or more dies.

[0028] In some examples, the die wafer comprises a complementary metal -oxide semiconductor (CMOS).

[0029] In some examples, the first carrier and the second carrier are each comprised of a material selected from the group consisting of: glass, quartz, silica, silicon, aluminum, and stainless steel.

[0030] In some examples, the first bonding material and the second bonding material comprise a bonding tape. [0031] In some examples, releasing the first carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

[0032] In some examples, releasing the second carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

[0033] In some examples, the first carrier is transparent and releasing the first carrier comprises applying heat or applying ultraviolet radiation to the first carrier.

[0034] In some examples, the first carrier is not transparent and releasing the first carrier comprises applying heat to the first carrier.

[0035] In some examples, the first carrier and the second carrier are transparent, releasing the first carrier and releasing the second carrier comprise applying UV radiation to the first carrier and to the second carrier, and a wavelength of UV radiation applied to release the first carrier is different than a wavelength of ultraviolet radiation applied to release the second carrier.

[0036] In some examples, releasing the first carrier comprises applying thermal energy to the first carrier, releasing the second carrier comprises applying thermal energy to the second carrier, and a temperature of the thermal energy applied for releasing the second carrier is greater than or equal to a temperature of the thermal energy applied for releasing the first carrier.

[0037] In some examples, the molding material comprises epoxy mold compound.

[0038] In some examples, the method further comprises: planarizing the surface of the molding material parallel to the planar surface of the first carrier.

[0039] In some examples, bonding the two or more dies to the first carrier comprises applying pressure to the first bonding material via the first carrier.

[0040] In some examples, bonding the two or more dies to the second carrier comprises applying pressure to the second bonding material via the second carrier.

[0041] 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. 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 package comprising a die encapsulated in a molding material, wherein a top surface of the sensor package comprises a detection surface of the die comprising one or more reaction sites and one or more electrical contact points, and portions of the molding material forming fanout areas at sidewalls of the die; a lidding layer over the detection surface oriented to define a fluidic channel over the detection surface, the lidding layer comprising an inlet and an outlet for fluid; and a carrier bonded to a bottom surface of the sensor package with a bonding material, wherein the bottom surface is parallel to the top surface.

[0042] In some examples, the apparatus further comprises a substrate comprising electrical contacts, the electrical contacts electrically coupled to the electrical contact points in the sensor package, where the substrate is bonded to the carrier.

[0043] 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 flow a cell. 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 in a flow cell, the flow cell comprising: a sensor package comprising a die encapsulated in a molding material, wherein a top surface of the sensor package comprises a detection surface of the die comprising one or more nanowells and one or more electrical contact points, and portions of the molding material forming fanout areas at sidewalls of the die, where the one or more nanowells comprise the reaction sites; a lidding layer over the detection surface oriented to define a fluidic channel over the detection surface, the lidding layer comprising an inlet and an outlet for fluid; a carrier bonded to a bottom surface of the sensor package with a bonding material, wherein the bottom surface is parallel to the top surface; and a substrate comprising electrical contacts, the electrical contacts electrically coupled to the electrical contact points in the sensor package, wherein the substrate is bonded to the carrier; exposing the reaction sites of the sensor package to light from a light source, wherein the light comprises excitation light and emitted light; and obtaining a signal from the sensor package.

[0044] 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.

[0045] It should be appreciated that all combinations of the foregoing aspects and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter and to achieve the advantages disclosed herein.

BRIEF DESCRIPTION OF THE DRAWINGS

[0046] 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:

FIGS. 1A-1B illustrate an example of a flow cell that can be formed utilizing aspects of the example workflows described herein;

FIGS. 2A-2B illustrate an example of a flow cell that can be formed utilizing aspects of the example workflows described herein;

FIG. 3 is an example of a general workflow that includes aspects integrated into examples of the methods for forming the flow cell of FIGS. 1A-1B;

FIG. 4 illustrates an example of the flow cells of FIGS. 1A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16; FIG. 5 illustrates an example of the flow cells of FIGS. 1 A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16;

FIG. 6 illustrates an example of the flow cells of FIGS. 1A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16;

FIG. 7 illustrates an example of the flow cells of FIGS. 1A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16;

FIG. 8 illustrates an example of the flow cells of FIGS. 1A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16;

FIG. 9 illustrates an example of the flow cells of FIGS. 1A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16;

FIG. 10 illustrates an example of the flow cells of FIGS. 1A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16;

FIG. 11 illustrates an example of the flow cell of FIGS. 1A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16;

FIG. 12 illustrates an example of the flow cells of FIGS. 1A-1B and 2A-2B during at least one stage in the formation of these flow cells in accordance with aspects of the workflows of FIG. 3 and FIG. 16;

FIG. 13 illustrates an example of the flow cell of FIGS. 1A-1B during at least one stage in the formation of this flow cell in accordance with aspects of the workflow of FIG. 3; FIG. 14 illustrates an example of the flow cell of FIGS. 1 A-1B during at least one stage in the formation of this flow cell in accordance with aspects of the workflow of FIG. 3;

FIG. 15 illustrates an example of the flow cell of FIGS. 1A-1B during at least one stage in the formation of this flow cell in accordance with aspects of the workflow of FIG. 3;

FIG. 16 is an example of a general workflow that includes aspects integrated into examples of the methods for forming the flow cell of FIGS. 2A-2B;

FIG. 17 illustrates some examples of the flow cell of FIGS. 2A-2B during at least one stage in the formation of this flow cell in accordance with aspects of the workflow of FIG. 16;

FIG. 18 illustrates some examples of the flow cell of FIGS. 2A-2B during at least one stage in the formation of this flow cell in accordance with aspects of the workflow of FIG. 16; and

FIG. 19 is an example of a general workflow that includes aspects integrated into examples of a method for utilizing the flow cell of FIGS. 1A-1B and 2A-2B.

DETAILED DESCRIPTION

[0047] 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.

[0048] 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 j oining of one component and another component with no intervening components therebetween (z.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.

[0049] The terms “including” and “comprising”, as used herein, mean the same thing.

[0050] 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%.

[0051] As used herein, a “flow cell” can include a device optionally having a lid extending over a reaction structure to form a fluidic 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 (optionally 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 fluidic 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 lightemitting 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.

[0052] 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.

[0053] 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/acqui sition. 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.

[0054] 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 Forster) resonance energy transfer (FRET), for example, by bringing a donor fluorophore in proximity to an acceptor fluorophore, decrease FRET by separating donor and acceptor fluorophores, increase fluorescence by separating a quencher from a fluorophore, or decrease fluorescence by co-locating a quencher and fluorophore. [0055] 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.

[0056] 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.

[0057] 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. Although nanowells are often used in the examples herein for illustrative purposes, the examples of flow cells depicted herein can include various functionalized sensor surfaces, including but not limited to surfaces of reaction recesses, such 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.

[0058] The terms “active surface” and “active area” and “active detection 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.

[0059] 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.

[0060] 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.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] 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 one or more signals. The sensors discussed in the examples herein may include image sensors such as front side illuminated sensors (FSIs) and back-side illuminated sensors (BSIs).

[0065] 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.

[0066] 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. The various examples are not limited to the arrangements and instrumentality shown in the drawings.

[0067] Warpage of a surface in a flow cell under a fluidic channel, a surface that includes the active detection area of the flow cell, adversely affects results of a reaction facilitated in the flow cell. In the examples herein, this surface includes a sensor or detector (e.g., CMOS) and fanout areas. Throughout this paper, the words detector and sensor are used interchangeably. The fanout packaging in these examples addresses this warpage concern. In flow cells, fanout areas are utilized to create additional fluidic flow areas that help optimize flow of sequencing reagents (fluids) over an active detection area. Sacrificing part of a sensor itself to create fanout areas is expensive and thus, previously proposed approaches utilize an EMC package to create the fanout surface beyond the active area. For the flow cell to function effectively, this fanout surface is flat and at a consistent height with the active area. However, EMC can warp during manufacture and if it does, the resultant flow cells will not function properly, especially over time. Disclosed herein are workflows for manufacturing flow cells with the fan-out regions with components that minimize these warpage concerns. Elements of the approach described herein produce flow cells with both flat fluidic fanouts area with minimal step height at the detector e.g., CMOS) to molding material (e.g., EMC) interface at the side-wall so as not to disturb the reagent flow and warpage-limited molded panels, thus minimizing or eliminating the wafer handleability concerns for downstream processing.

[0068] FIGS. 1 A-1B (collectively referred to FIG. 1) and FIGS. 2A-2B (collectively referred to as FIG. 2) illustrate flow cells 101 201 formed using techniques described herein. FIGS. 1A-1B and FIGS. 2A-2B all illustrated cross-sections, but FIGS. IB and 2B show an orthogonal crosssection and hence the electrical connections (bond pads 135a-135b 235a-235b, electrical connections 148 248 to the bond pads 135a- 135b 235a-235b, and vias 149 249 that each connect the electrical connections 158 248 to the bond pads to electrical connections 181 281 at the base of the substrate 173 183). FIG. IB and FIG. 2B illustrate the electrical connections 148 248 (which can be wire bound connections) in different planes and in neither case, in these examples, is the electrical connection 148 248 made through the molding material 176 276, which can be comprised of an epoxy mold compound (EMC), in a non-limiting example.

[0069] FIG. 3 illustrates an exemplary workflow 300 for forming the flow cell 101 of FIG. 1 while FIG. 16 illustrates an exemplary workflow 1600 for forming the flow cell 201 of FIG. 2. As illustrated in FIGS. 4-15, and 17-18, which add illustrative details to the workflows 300 1600, both workflows 300 1600 include supporting molding material (e.g., an EMC wafer), which will form the fanout areas of a flow cell 101 201, with at least one support substrate or carrier. Although FIGS. 1 -2, 4-15, and 17-18 and illustrate aspects of controlling warpage in the formation of flow cell with a fanout area comprised of a molding material e.g., EMC), and in doing so, employing a wafer that is circular, the shape of the wafer is merely illustrative as the techniques in the exemplary workflows herein can be utilized across differing wafer shapes.

[0070] FIGS. 1 and 2 illustrate flow cells 101 201 formed using techniques described herein. These resultant flow cells 101 201 have many similarities and their structural differences are based on differences in the workflows 300 (FIG. 3) 1600 (FIG. 16) utilized to form these flow cells 101 201, which will be discussed herein. Although both workflows 300 (FIG. 3) 1600 (FIG. 16) include utilizing two carriers to control warpage of a fanout area, only the flow cell 201 of FIG. 2 includes one of the carriers in the resultant flow cell 201. Before the workflows 300 (FIG. 3) 1600 (FIG. 16) are reviewed, the structure of the resultant flow cells 101 201 is discussed. [0071] In FIGS. 1 and 2, the flow cell 101 201 includes additional fluidic areas, i.e., a fanout areas 11 la-11 lb 21 la-21 lb, outside of the active detection area 121 221 in the sensor 125 225 or detector of the flow cell 101 201. The fanout areas 11 la-11 lb 21 la-21 lb help optimize flow of sequencing reagents (fluids) over the active detection area 121 221. The active detection area 121 221 is a (top) surface of a sensor 125 225 (e.g., CMOS). As illustrated in FIGS. 1-2, the active detection area 121 221 includes nanowells 131 231. The number of nanowells 131 231 is provided as a non-limiting example. The (top) surface of the sensor 125 225 also includes bond pads 135a-135b 235a-235b to which electrical vias (not pictured) can be affixed (e.g., wire- bonded). Different types of flow cells can include different numbers of bond pads as well as different orientations for the bond pads 135a-135b 235a-235b on the sensor 125 225 relative to the active detection area 121 221. Two bond pads 135a- 135b 235a-235b are provided in this example just for illustrative purposes and not to suggest any limitations. Thus, a top surface 153 253 of the package 164 174 (the package includes molding material 176 276 encapsulating one or more sensors 125 225). The configuration of the 135a- 135b 235a-235b of the flow cells 101 201 in FIGS. 1-2 is provided by way of example, for illustrative purposes only, and not to suggest any limitations.

[0072] In the flow cells 101 201, a fluidic channel 141 241 is capped with a lidding layer 161 261. In these examples, the lidding layer 161 261 can be glass to enable exposure of the active detection area 121 221 (and hence, the sequencing reagents) to light from a light source (not pictured) to enable detecting various reactions. The lidding layer 161 261 includes an inlet 151 251 and an outlet 171 271 for the fluids to enter and to exit the fluidic channel 141 241. In this example, the lidding layer 161 and molding material 176 are not in direct contact and are separated by an intermediate layer 127 (e.g., spacer or interposer layer).

[0073] As will be discussed in greater detail herein, the fanout areas 11 la-11 lb 21 la-21 lb are formed by surfaces comprised of molding material (e.g., EMC) 176276. During the formation of the flow cell, the molding material 176 276 is molded around one or more sensors 125 225, encapsulating the one or more sensors 125 225. In the flow cell 101 of FIG. 1, a (bottom) surface 178 of the molding material 176 which is parallel to the (top) surface 153 of the package 164 of the molding material 176 that includes the fanout areas 11 la-11 lb, is attached to a substrate 173. The substrate 173 can encapsulate various electrical connections such as vias 149 that electrically couple electrical connections 148 (e.g., wires) from the bond pads 135a- 135b to electrical connections 181 at the base of the substrate 173. In FIG. 2, a surface 278 of the molding material 276 which is parallel to the surface of the molding material 276 that forms the fanout area 211 is attached to a carrier 289 and the carrier 289 is attached to the substrate 273. As will be discussed herein, the carrier 289 provides structural integrity to the top surface 253 of the flow cell 201, and especially the fanout areas 21 la-21 lb.

[0074] As noted earlier, workflows 300 (FIG. 3) 1600 (FIG. 16) utilized to form both flow cells 101 201 include bonding or affixing a package 164 264 that includes molding material 176 276 encapsulating one or more sensors 125 225 to two carriers, to reduce or prevent warpage of the fanout areas 11 la-11 lb 21 la-21 lb. In the flow cell 101 of FIG. 1, both these carriers are removed before a resultant stack 192 (e.g., the lidding layer 161, separated by an intermediate layer 127 (e.g., spacer or interposer layer) which is in contact with the lidding layer 161 and the molding material 176, the molding material 176, and sensor 125 package 164) is attached to a substrate 173. In FIG. 2, though, the resultant stack 293 also includes a carrier 289 (referred to as a second carrier in the workflows described herein). Utilizing an adhesive or other bonding material 263, this carrier 289 is bonded or attached to the surface 278 of the molding material 276 which is parallel to the top surface 253 that includes the portions of the molding material 276 that form the fanout areas 21 la-21 lb. Thus, in the flow cell of FIG. 2, the substrate 273 encapsulates various electrical connections such as vias 249 that electrically couple electrical connections 248 (e.g., wires) from the bond pads 235 to electrical connections 280 at the base of the substrate 273, which is attached to the carrier 289.

[0075] FIG. 3 is a workflow 300 that provides an overview of a process for forming the flow cell 101 illustrated in FIG. 1. Various aspects in FIG. 3 are further illustrated in FIGS. 4-15. Thus, as the workflow 300 is described, aspects of FIGS. 4-15 are referenced to provide non-limiting examples (provided for illustrative purposes only) of various aspects of the workflow 300.

[0076] The workflow 300 of FIG. 3 commences, as illustrated in FIG. 4, when one singulates a die 423 into what will become individual sensors or detectors 425a-425c (310). Once singulated into individual sensors 425a-425c each sensor 425a-425c comprises what will become an active detection area 421a-421c. Different technologies can be utilized to singulate this die 423 (e.g., CMOS), including but not limited to using saw-dicing and/or stealth dicing. Once the die 423 has been singulated into what will become individual sensors 425a-425c in flow cells (e.g., FIG. 1, 101), as illustrated in FIG. 5, one bonds the sensors 525a-525b to a first carrier 587 (320). The sensors 525a-525b can be bonded to the first carrier 587 using a bonding material 518. A surface of each (now singulated) sensor 525a-525b bonded to the first carrier comprises what will become the active detection area 521a-521b of the sensor 525a-525b.

[0077] The carriers in these examples, including the first carrier 587 (FIG. 5), and yet-to-be- discussed second carrier (e.g., FIG. 2, 289) are attached to the packages (e.g., FIGS. 1-2, 164 264) (which include one or more sensors (e.g., FIGS. 1-2, 125 225) encapsulated in a molding material (e.g., FIGS. 1-2, 175 275), such as EMC) to reduce or prevent warpage of a fanout areas (e.g., FIGS. 1-2, 11 la-11 lb, 21 la-21 lb). Materials utilized to form the carrier can vary based on factors including, but not limited to, whether the carrier will remain in the final flow cell (e.g., FIG. 2, 289). One selects the material of the carrier and a bonding material utilized to bond the sensor and/or the package (which includes the sensor and the molding material) to a carrier (to prevent or mitigate warpage) together because the bonding material is selected to stay bonded and/or to release at various points in the processes described herein. The material of the carrier can affect the outside trigger (e.g., thermal energy or UV light) which can access the bonding material to allow for bonding and releasing (e.g., de-bonding) at planned intervals when forming the flow cell. In some examples, including some when the carrier is ultimately removed before formation of the flow cell is completed (see, e.g., FIG. 1, 101), any rigid material can be utilized as a carrier. Examples of carriers can include, but are not limited to, silicon, aluminum, and/or stainless steel, for a non-transparent carrier, and glass, quartz, and/or fused silica, for a transparent carrier. Thickness of the carrier can vary depending on the pressure that the carrier and the package is subjected to during formation of the resultant flow cell as well as the heat and/or pressure the resultant flow cell is subjected to during use (if the carrier is retained). In some examples, one can select a carrier with a thickness of approximately 0.5mm to approximately 2mm.

[0078] As illustrated in FIG. 5, the sensors 525a-525b (which can be singulated from the die and spaced at a distance on an x-axis from each other, e.g., a lateral distance) are bonded to a first carrier 587 (320) utilizing a bonding material 518, including not limited to, a tape. To preserve the integrity of the resultant flow cell, various considerations can be weighed to select a bonding material that is complementary to the carrier as well as to the workflow of forming the flow cell as well as to the operation of the resultant flow cell. In some examples, the bonding material 518 is pressure sensitive because forming the flow cell will involve applying pressure to the various elements. Additionally, this first carrier 587, in both this workflow 300 as well as the workflow 1600 of FIG. 16 (which illustrates forming the flow cell 201 of FIG. 2) is temporarily bonded (by a bonding material 518) to the sensors 525a-525b and is later released. In various examples one may select a bonding material 587 that releases using one of more of UV light or thermal energy. In some examples, if the carrier 587 is transparent (e.g., glass, quartz, and/or fused silica), one may select a bonding material 518 that releases upon exposure to UV light. If the carrier 587 is not transparent (e.g., silicon, aluminum, and/or stainless steel), one may select a bonding 518 material that releases upon exposure to thermal energy. The first carrier 587 is a temporary carrier, meaning that one removes the carrier before completing formation of the flow cell (e.g., FIG. 1, 101). In some examples, if the first carrier 587 is not transparent, one selects a thermal release bonding material 518 (e.g., tape). However, if the first carrier 587 is transparent, one can select either a thermal or a UV release bonding material 518 (e.g., tape).

[0079] Returning to FIG. 3 and as illustrated in FIG. 6, after utilizing a bonding material 618 to bond the singulated sensors 625a-625b to a first carrier 687 at a (e.g., lateral) distance from each other (320), one can encapsulate the sensors (dies) in molding material 676 (e.g., EMC material) (330). Techniques including, but not limited to, a transfer or compression molding technique can be utilized to encapsulate the sensors 625a-625b with the molding material 676. When encapsulating the sensors 625a-625b, the molding material 676, because it is molded to the carrier 676 at the same surface where the sensors 625a-625b are attached, a surface is formed that includes the molding material 676 and the active detection area 621a-621b of the sensors 625a-625b. The molding material surface adjacent to the sensors 625a-625b can form fanout areas 61 la-611c (or portions of fanout areas) in the eventual flow cell. In some examples, as illustrated in FIG. 7, one can planarize (e.g., grind) a surface 778 of the molding material 776 that is parallel (at a longitudinal distance) from the surface of the molding material 776 that will form the fanout areas 71 la-711c (or part of the fanout areas) so that the (cured) molding material 776 is of a uniform thickness across the wafer (e.g., the package 764 is of a uniform thickness) (340). [0080] As illustrated in FIG. 8, the workflow 300 includes bonding a second carrier 889 to the package 864 (e.g., the molding material 876 and the sensors 825a-825b) (350). This second carrier 889 can be laminated or otherwise bonded or attached to the package 864 using a second bonding material 863. As illustrated in FIG. 8, using a bonding material 863, one can bond a second carrier 889 to a surface 878 of the package 864 opposing the first carrier 887 (350). In this example, like the first carrier 887, the second carrier 889, is eventually released, meaning that both carriers are only temporarily attached to the package 876 (to reduce or prevent warpage during the formation of the resultant flow cell (e.g., FIG. 1, 101)). If the bonding materials 818 863 used to attach both the first carrier 887 and the second carrier 889 are thermal release bonding materials (e.g., tape), in some examples, one selects two different bonding materials such that the temperature applied to release the second carrier 889 is greater than the temperature applied to release the first carrier 887. Thus, the first bonding material 818 and the second bonding material 863 are selected to be released with this temperature differential in mind. If the bonding materials 818 863 used to attach both the first carrier 887 and the second carrier 889 to the package 864 are UV release bonding materials (e.g., tape), in some examples, one selects bonding materials 818 863 so that the wavelength applied to release the second carrier 889 is different than the wavelength applied to release the first carrier 887.

[0081] As illustrated in FIG. 9, after bonding the second carrier 989 to the package 964 (350), one can flip (e.g., re-orient) the stack 933 (the combination of the first carrier 987, the second carrier 989, and the package 964) one hundred and eighty degrees (360). After re-orienting this stack 933, the first carrier 987 is atop the stack 933. Once the first carrier 987 is atop the stack, release the first carrier 987 from the stack 933 (370). As illustrated in FIG. 10, releasing the first carrier 987 (FIG. 9) (370) exposes a surface of the (now) top surface 1053 which includes the active detection areas I02Ia-1021b of the sensors 1025a-1025b and the portions of the molding material 1076 which will become fanout areas 101 la-1011c or part of these areas.

[0082] Returning to FIG. 9, how one releases the first carrier 987 is dependent upon the bonding material 918 used to bond the first carrier 987 to the sensors 925a-925b (or vice versa). If the bonding material 918 releases when exposed to UV light, then one can expose the first carrier 987 (provided it is transparent) to UV light to release the first carrier 987 from the stack 933. If the bonding material 918 is a material that releases when exposed to thermal energy, then one can release the first carrier 987 (which can be either transparent or not transparent) by exposing it to thermal energy of a temperature which will activate the release. The bonding material 918 selected is also selected so that it will leave minimal residue (as will be discussed later herein, the second bonding material 963 can also be selected based on this quality). In some examples, the bonding material 918, when released, does not leave any residue. However, should the boding material leave residue (which is desired or tolerated to be at least minimal in some examples), referring to FIG. 10, one can clean the residue from the top surface 1053, the surface of the package 1064 that includes the active detection areas 102 la- 102 lb and what will become the fanout areas 101 la-1011c (formed by the molding compound). A simple solvent can be utilized to remove the residue and avoid damaging the active detection areas 1021a-1021b. Once the carrier has been released (370), as illustrated in FIG. 11, one can apply wafer level chemistry 1129 to the active detection areas 1121a- 1121b of the sensors 1125a- 1125b (375).

[0083] FIG. 11 illustrates applying wafer level chemistry, which may be applied to all or a portion of the sensor surface (z.e., a “functionalized coating”) to facilitate immobilizing biomolecules (or biological or chemical substances) thereto. The functionalized coating may include a plurality of functionalized molecules, which in some aspects include polymer coatings covalently attached to the surface of a passivation layer over the substrate. The polymer coatings, such as poly(N-(5-azidoacetamidylpentyl)acrylamide-co-acrylamide) (PAZAM), are used in the formation and manipulation of substrates, such as molecular arrays and flow cells. In applying this chemistry, a sensor surface may be coated, in at least one area, by using beads coated with a covalently attached polymer, such as PAZAM, and used, in the resultant flow cell, in determining a nucleotide sequence of a polynucleotide attached to a substrate surface, in some aspects. In some examples, nucleic acids can be immobilized to the functionalized sensor surface, such as to surfaces of reaction recesses, which in the examples of FIGS. 1-2 are nanowells. Natural nucleotides and enzymes that are configured to interact with the natural nucleotides may be utilized. Natural nucleotides include, for example, ribonucleotides or deoxyribonucleotides. Natural nucleotides can be in the mono-, di-, or tri-phosphate form and can have a base selected from adenine (A), Thymine (T), uracil (U), guanine (G) or cytosine (C). It will be understood, however, that non-natural nucleotides, modified nucleotides or analogs of the aforementioned nucleotides can be utilized. [0084] As illustrated in FIGS. 3 and 12, one can place a lidding layer 1261 over the top surface 1253, defining a fluidic channel 1241a-1241b above each active detection area 1221a-1221b (380). FIG. 12, in addition to FIGS. 4-11, illustrate the formation of two flow cells. However, this number was chosen for illustrative purposes only and provides a non-limiting example. One or more flow cells can be formed utilizing the processes and aspects of the processes described herein. FIG. 12 illustrates two sensors 1225a-1225b, each of which can be utilized in a flow cell (e.g., FIG. 1, 101), each flow cell to include a lidding layer 1261 (e.g., glass) placed/oriented over an active detection area 1221a-1221b, defining a fluidic channel 1241a-1241b over this top surface 1253. The top surface 1253 includes the contiguous surface of the active detection area 1221a-1221b and (what will become) fanout areas 121 la-1211c (comprised of a molding material 1276). Each resultant flow cell can include a flat fluidic fanout 121 la-1211c area abutting the sidewall of the sensor 1225a-1225b with minimal step height at the sensor 1225a- 1225b. The lidding layer 1261 includes openings that serve as either inlets 1251a-1251b or outlets 1271a-1271b during the sequencing or other operations performed in the flow cells. In some examples, the lidding layer is laminated or otherwise bonded to a portion of the package 1264.

[0085] As illustrated in FIG. 13, once the lidding layer 1361 is attached to the material 1263 (FIG. 12) via an intermediate layer 1327 (e.g., an interposer or a spacer) (380), one can release the second carrier 1289 (FIG. 12) by releasing the second bonding material 1263 (FIG. 12) (385). FIG. 13 depicts the sensor package 1364 with the lidding layer 1361 attached after the second carrier 1289 (FIG. 12) is released. Releasing the second carrier 1389 (385) exposes the (bottom) surface 1378 of the package comprised of the molding material 1376; this surface which opposes the top surface 1353, which includes the active detection areas 1321a-1321b of the sensors 1325a-1325b.

[0086] As with releasing the first carrier (see, e.g., FIG. 9, 987 and FIG. 10), how one releases the second carrier (see, e.g., FIG. 12, 1289 and FIG. 13) is dependent upon the bonding material 1263 (FIG. 12) used to bond the second carrier 1289 (FIG. 12) to the molding material 1276 (or vice versa). If the bonding material 1263 releases when exposed to UV light, then one can expose the second carrier 1289 (provided it is transparent) to UV light to release the second carrier 1289. If the bonding material 1263 is a type that releases when exposed to thermal energy, then one can release the second carrier 1289 (which can be either transparent or not transparent) by exposing it to thermal energy of a temperature which will activate the release. Should the bonding material leave a residue, one can clean the residue from the surface of the molding material 1276 with a simple solvent. In some examples, the bonding material 1263 is a tape that does not leave a residue.

[0087] After releasing the second carrier (385), as illustrated in FIGS. 14-15, one can singulate the remainder of the stack 1442 into individual flow cell packages 1416a-1416b 1516a-l 516b, ready for attachment to a substrate (as illustrated in FIG. 1) (390). Each resultant flow cell package 1416a-1416b 1516a-1516b includes an inlet 1451a-1451b 1551a-1551b and an outlet 1471a-1471b 1571a-1571b in the lidding layer 1416a-1416b 1516a-1516b. The individual flow cells packages 1416a-1416b 1516a- 1516b can then each be assembled into individual flow cells like the flow cell 101 of FIG. 1 by electrically connecting the bond pads 135 to electrical connections 181 at the base of a substrate 173 via electrical vias or connections (not depicted) and encapsulating the connections in the substrate 173 (395). These connections can be made using wire-bonding.

[0088] As aforementioned and illustrated in FIG. 2, a resultant flow cell 201 can also include a carrier when formed using a workflow 1600 where the second carrier 289 (FIG. 2) is not released. FIG. 16 provides an overview of this workflow 1600. The workflow 1600 of FIG. 16 is similar to the workflow 300 of FIG. 300 except that the second carrier 289 (FIG. 12) is not released from the stack and becomes part of the resultant flow cell 201 (FIG. 2). This second carrier 289 acts as a support for the flow cell 201 and specifically, for the fanout areas 21 la-21 lb comprised of molding compound 276. The second workflow 1600 is illustrated with FIGS. 4-12, however, but because the second carrier 289 (FIG. 1) is not released in this workflow 1600, FIGS. 17-18 illustrate latter aspects of the workflow 1600.

[0089] Referring to FIGS. 4 and 16, one can singulate a die 423 into what will become individual sensors 425a-425c (1610). Per FIG. 5, one can then utilize a bonding material 518 to bond the singulated sensors 525a-525b to a first carrier 587 at a lateral distance from each other (1620). As is the case with the flow cells formed using the workflow 300 of FIG. 3, in this workflow 1600, the combination of the materials used for the first carrier and the second carrier are selected to enable the first carrier to be released at a particular time during the formation of the flow cell. If the first carrier is transparent (e.g., glass, quartz, fused silica, etc.) the bonding material can be either a UV-release bonding material or a thermal release bonding material and if the first carrier is not transparent (e.g., silicon, aluminum, stainless steel, etc.), the bonding material can be a thermal release material. In some examples, the carrier has a thickness in the range of approximately 0.5mm to approximately 2.0mm. As illustrated in FIG. 6, once the dies or individual sensors 625a-625b are bonded to the first carrier 687, one can encapsulate the dies or individual sensors 625a-625b in molding material 676 (e.g., EMC material) (1630). As illustrated in FIG. 7, one can planarize (e.g., grind) a surface 778 of the molding material 776 that is parallel (at a longitudinal distance) from the surface of the molding material 776 forming the fanout areas 71 la-711c (which will be the top surface 753) so that the molding material 776 is of a uniform thickness across the wafer package 764 (1640) (see, e.g., FIG. 7). Per FIG. 8, one can bond a second carrier 889 to the package 864 (e.g., the molding material and the sensors) (1650) creating a stack that includes, from the top down, the second carrier 889, the package 864, and the first carrier 887. As illustrated in FIG. 9, one can re-orient this stack 933 by flipping it one hundred and eighty degrees such that the first carrier 987 is on top (1660). One can then release the first carrier 987 (which is atop the stack) from the stack (1670). Per FIG. 10, releasing the first carrier (1670) exposes the active detection areas 1021a-1021b on the sensors and the surfaces of the molding material that are contiguous with the active detection areas 102 la- 102 lb that will become the fanout areas 101 la- 1011c. As illustrated in FIG. 11, one can apply wafer level chemistry 1129 to the active detection areas 1121 a- 1121b of the sensors 1125a-l 125b (1675). Once the chemistry is applied, as illustrated in FIG. 12, one can orient a lidding layer 1261 over the top surface 1253, that includes the active detection areas 1221a- 1221b and the portions of the mold compound that will form the fanout areas 121 la-1211c, defining a fluidic channel (1680) (see, e.g., FIG. 11). After this aspect, the workflow 1600 diverges from the workflow 300 of FIG. 3.

[0090] Rather than release the second carrier, in the workflow 1600 of FIG. 6, retain the second carrier 1789 (FIG. 17) in the resultant flow cells (see, e.g., FIG. 2). Thus, as illustrated in FIGS. 17 and 18, one can singulate the stack, which includes the lidding layer 1751, the package 1764 (which includes the molding material 1776 and the sensors 1725a- 1725b), and the second carrier 1789 (bonded with the bonding material 1763, into individual flow cell packages 1717a-1717b 1817a-1817b (1685). These resultant singulated flow cell packages 1817a-l 817b, illustrated in FIG. 18, can be assembled into flow cells, such as the flow cell 201 of FIG. 2. The individual flow cells packages 1817a- 1817b can then each be assembled into individual flow cells 201 by electrically connecting the bond pads 235 to electrical connections 281 at the base of a substrate 273 via electrical vias or connections (not depicted) and encapsulating the connections in the substrate 273 (390). These connections can be made using wire-bonding (1690). In this example, this assembly includes bonding the glass carrier 289 to the substrate 273 through which the electrical connections are made.

[0091] FIG. 19 is an example of a workflow 1900 that describes utilizing one or more of the examples of the flow cells described herein (e.g., FIG. 1, 101, FIG. 2, 201). FIG. 19 is provided as an illustrative example and does not suggest any limitations to how the flow cells 101 201 described herein can be utilized. The flow cell utilized in this workflow 1900, of which examples are illustrated in FIGS. 1-2 can include a sensor package (e.g., a die encapsulated in a molding material, where a top surface of the sensor package comprises a detection surface of the die comprising one or more nanowells and one or more electrical contact points, and portions of the molding material forming fanout areas at sidewalls of the die, where the nanowells comprise the reaction sites), a lidding layer (including an inlet and an outlet for fluid) over the detection surface oriented to define a fluidic channel over the detection surface, a carrier bonded to a bottom surface of the sensor package with a bonding material, wherein the bottom surface is parallel to the top surface, and a substrate comprising electrical contacts, the electrical contacts electrically coupled to the electrical contact points in the sensor package, wherein the substrate is bonded to the carrier. As illustrated in the workflow, to utilize the flow cell (e.g., 101 201), one places one or more nucleic acids in reaction sites of a sensor in a flow cell (1910). One exposes the reaction sites of the sensor package to light from a light source (e.g., excitation light and emitted light) (1920). One obtains a signal from the sensor package (1930).

[0092] In one aspect, a method is provided, for example, a method of forming a flow cell. The method can include: bonding a die to a first carrier with a first bonding material, wherein a surface of the first carrier bonded to a given surface of die comprises a larger surface area than the given surface of the die, wherein the first bonding material covers the surface of the first carrier, wherein the given surface of the die comprises one or more reaction sites and one or more electrical contact points; encapsulating the die with a molding material, wherein portions of the molding material are flush to portions of the first bonding material; bonding a second carrier to a surface of the molding material with a second bonding material, wherein the surface of the first carrier and the surface of the molding material are parallel; releasing the first carrier from the die encapsulated with the molding material to expose a surface comprising the given surface of the die and the portions of the molding material, wherein the portions of the molding material comprise fanout regions; applying chemistry to the given surface of the die such that the given surface of the die becomes an active detection area; and placing a lidding layer over the surface comprising the given surface of the die and the portions of the molding material to form a space over the active detection area, wherein the space defines a fluidic channel.

[0093] In some examples, the method further comprises: releasing the second carrier from the surface of the molding material, orienting the die on the substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, where the substrate comprises electrical contact, and connecting the electrical contacts of the substrate to the electrical contact points of the die.

[0094] In some examples, the method further comprises: orienting the die on the substrate such that the second carrier is adjacent to an upper surface of the substrate, where the substrate comprises electrical contacts, and connecting the electrical contacts of the substrate to the electrical contact points of the die.

[0095] In some examples, the die comprises a complementary metal -oxide semiconductor (CMOS).

[0096] In some examples, the first carrier and the second carrier are each comprised of a material selected from the group consisting of: glass, quartz, silica, silicon, aluminum, and stainless steel.

[0097] In some examples, the method further comprises: prior to bonding the second carrier to a surface of the molding material with a second bonding material, planarizing the surface of the molding material.

[0098] In some examples, releasing the first carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material. [0099] In some examples, releasing the second carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

[0100] In some examples, the first carrier is transparent and releasing the first carrier comprises applying heat or applying ultraviolet radiation to the first carrier.

[0101] In some examples, the first carrier is not transparent and releasing the first carrier comprises applying heat to the first carrier.

[0102] In some examples, the first carrier and the second carrier are transparent, releasing the first carrier and releasing the second carrier comprise applying UV radiation to the first carrier and to the second carrier, and a wavelength of UV radiation applied to release the first carrier is different than a wavelength of ultraviolet radiation applied to release the second carrier.

[0103] In some examples, releasing the first carrier comprises applying thermal energy to the first carrier, releasing the second carrier comprises applying thermal energy to the second carrier, and a temperature of the thermal energy applied for releasing the second carrier is greater than or equal to a temperature of the thermal energy applied for releasing the first carrier.

[0104] In some examples, the surface of the first carrier and the given surface of the die are planar surfaces.

[0105] In some examples, the molding material comprises epoxy mold compound.

[0106] In some examples, bonding a die to a first carrier with a first bonding material comprises: prior to the bonding, singulating the die into portions, where each portion of the die comprises at least one reaction site of the one or more reaction sites, and orienting the portions of the die on the first bonding material at a lateral distance from each other.

[0107] In some examples, placing the lidding layer over the surface comprises forming a stack and the method further comprises: modifying the stack by releasing the second carrier from the surface of the molding material; singulating the modified stack into packages, wherein each package comprises a given portion of the portions of the die; orienting at least one package on a substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the given portion of the die.

[0108] In some examples, placing the lidding layer over the surface comprises forming a stack and the method further comprises: singulating the stack into packages, wherein each package comprises a given portion of the portions of the die; orienting at least one package on a substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the given portion of the die.

[0109] In one aspect, a method is provided, for example, a method of forming flow cells. The method can include: forming die packages, comprising: depositing a first bonding material on a planar surface of a first carrier; bonding two or more dies to the first carrier, the bonding comprising orienting the two or more dies on the first bonding material such that the first bonding material bonds the two or more dies to the first carrier, wherein the orienting comprises placing the two or more dies on the planar surface at orientations wherein each die of the two or more dies is at a lateral distance from a next die of the two or more dies, wherein each die comprises one or more nanowells and one or more electrical contact points, wherein the nanowells are coupled to the first bonding material; encapsulating the two or more dies with a molding material, wherein portions of the molding material are flush to portions of the first bonding material; bonding a second carrier to a surface of the molding material with a second bonding material, wherein the planar surface of the first carrier and the surface of the molding material are parallel and separated by a longitudinal distance; releasing the first carrier from the die encapsulated with the molding material to expose surfaces of the two or more dies comprising the nanowells and the portions of the molding material; and applying chemistry to surfaces of the two or more dies comprising the nanowells such that the surfaces of the two or more dies comprising the nanowells become active detection areas.

[0110] In some examples, forming the die packages further comprises: releasing the second carrier from the surface of the molding material; and dicing through the molding material to separate the two or more dies into individual die packages, wherein each die package comprises a die of the two or more dies and part of portions of the molding material comprising fanout regions on each side of the die of the two or more dies, wherein a top surface of each die package comprises an active detection areas of the active detection areas.

[0111] In some examples, the method further comprises: dicing through the molding material and the second carrier to separate the two or more dies into individual die packages, wherein each die package comprises a die of the two or more dies and part of portions of the molding material comprising fanout regions on each side of the die of the two or more dies, wherein a top surface of each die package comprises an active detection areas of the active detection areas.

[0112] In some examples, the method further comprises: orienting an individual die package of the individual die packages on a substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the individual die package.

[0113] In some examples, the method further comprises: singulating a die wafer to form the two or more dies.

[0114] In some examples, the die wafer comprises a complementary metal -oxide semiconductor (CMOS).

[0115] In some examples, the first carrier and the second carrier are each comprised of a material selected from the group consisting of: glass, quartz, silica, silicon, aluminum, and stainless steel.

[0116] In some examples, the first bonding material and the second bonding material comprise a bonding tape.

[0117] In some examples, releasing the first carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

[0118] In some examples, releasing the second carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

[0119] In some examples, the first carrier is transparent and releasing the first carrier comprises applying heat or applying ultraviolet radiation to the first carrier. [0120] In some examples, the first carrier is not transparent and releasing the first carrier comprises applying heat to the first carrier.

[0121] In some examples, the first carrier and the second carrier are transparent, releasing the first carrier and releasing the second carrier comprise applying UV radiation to the first carrier and to the second carrier, and a wavelength of UV radiation applied to release the first carrier is different than a wavelength of ultraviolet radiation applied to release the second carrier.

[0122] In some examples, releasing the first carrier comprises applying thermal energy to the first carrier, releasing the second carrier comprises applying thermal energy to the second carrier, and a temperature of the thermal energy applied for releasing the second carrier is greater than or equal to a temperature of the thermal energy applied for releasing the first carrier.

[0123] In some examples, the molding material comprises epoxy mold compound.

[0124] In some examples, the method further comprises: planarizing the surface of the molding material parallel to the planar surface of the first carrier.

[0125] In some examples, bonding the two or more dies to the first carrier comprises applying pressure to the first bonding material via the first carrier.

[0126] In some examples, bonding the two or more dies to the second carrier comprises applying pressure to the second bonding material via the second carrier.

[0127] In one aspect, an apparatus is provided. The apparatus can include: a sensor package comprising a die encapsulated in a molding material, wherein a top surface of the sensor package comprises a detection surface of the die comprising one or more reaction sites and one or more electrical contact points, and portions of the molding material forming fanout areas at sidewalls of the die; a lidding layer over the detection surface oriented to define a fluidic channel over the detection surface, the lidding layer comprising an inlet and an outlet for fluid; and a carrier bonded to a bottom surface of the sensor package with a bonding material, wherein the bottom surface is parallel to the top surface. [0128] In some examples, the apparatus further comprises a substrate comprising electrical contacts, the electrical contacts electrically coupled to the electrical contact points in the sensor package, where the substrate is bonded to the carrier.

[0129] In one aspect, a method is provided, for example, a method for utilizing a flow cells. The method can include: placing one or more nucleic acids in reaction sites of a sensor in a flow cell, the flow cell comprising: a sensor package comprising a die encapsulated in a molding material, wherein a top surface of the sensor package comprises a detection surface of the die comprising one or more nanowells and one or more electrical contact points, and portions of the molding material forming fanout areas at sidewalls of the die, where the one or more nanowells comprise the reaction sites; a lidding layer over the detection surface oriented to define a fluidic channel over the detection surface, the lidding layer comprising an inlet and an outlet for fluid; a carrier bonded to a bottom surface of the sensor package with a bonding material, wherein the bottom surface is parallel to the top surface; and a substrate comprising electrical contacts, the electrical contacts electrically coupled to the electrical contact points in the sensor package, wherein the substrate is bonded to the carrier; exposing the reaction sites of the sensor package to light from a light source, wherein the light comprises excitation light and emitted light; and obtaining a signal from the sensor package.

[0130] 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. [0131] 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.

[0132] 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.

[0133] 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.

[0134] 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.

[0135] 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.

[0136] 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.

Claims

CLAIMS What is claimed is:

1. A method, comprising: bonding a die to a first carrier with a first bonding material, wherein a surface of the first carrier bonded to a given surface of die comprises a larger surface area than the given surface of the die, wherein the first bonding material covers the surface of the first carrier, wherein the given surface of the die comprises one or more reaction sites and one or more electrical contact points; encapsulating the die with a molding material, wherein portions of the molding material are flush to portions of the first bonding material; bonding a second carrier to a surface of the molding material with a second bonding material, wherein the surface of the first carrier and the surface of the molding material are parallel; releasing the first carrier from the die encapsulated with the molding material to expose a surface comprising the given surface of the die and the portions of the molding material, wherein the portions of the molding material comprise fanout regions; applying chemistry to the given surface of the die such that the given surface of the die becomes an active detection area; and placing a lidding layer over the surface comprising the given surface of the die and the portions of the molding material to form a space over the active detection area, wherein the space defines a fluidic channel.

2. The method of claim 1, further comprising: releasing the second carrier from the surface of the molding material; orienting the die on a substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the die.

3. The method of claim 1, further comprising: orienting the die on a substrate such that the second carrier is adjacent to an upper surface of the substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the die.

4. The method of any one of claims 1-3, wherein the die comprises a complementary metal-oxide semiconductor (CMOS).

5. The method of any one of claims 1-4, wherein the first carrier and the second carrier are each comprised of a material selected from the group consisting of: glass, quartz, silica, silicon, aluminum, and stainless steel.

6. The method of any one of claims 1-5, further comprising: prior to bonding the second carrier to a surface of the molding material with a second bonding material, planarizing the surface of the molding material.

7. The method of any one of claims 1-6, wherein releasing the first carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

8. The method of claim 2, wherein releasing the second carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

9. The method of any one of claims 1-4, wherein the first carrier is transparent and wherein releasing the first carrier comprises applying heat or applying ultraviolet radiation to the first carrier.

10. The method of any one of claims 1-4, wherein the first carrier is not transparent and wherein releasing the first carrier comprises applying heat to the first carrier.

11. The method of claim 2, wherein the first carrier and the second carrier are transparent, wherein releasing the first carrier and releasing the second carrier comprise applying UV radiation to the first carrier and to the second carrier, and wherein a wavelength of UV radiation applied to release the first carrier is different than a wavelength of ultraviolet radiation applied to release the second carrier.

12. The method of claim 2, wherein releasing the first carrier comprises applying thermal energy to the first carrier, wherein releasing the second carrier comprises applying thermal energy to the second carrier, and wherein a temperature of the thermal energy applied for releasing the second carrier is greater than or equal to a temperature of the thermal energy applied for releasing the first carrier.

13. The method of any one of claims 1 -12, wherein the surface of the first carrier and the given surface of the die are planar surfaces.

14. The method of any one of claims 1-13, wherein the molding material comprises epoxy mold compound.

15. The method of claim 1, wherein bonding the die to the first carrier with the first bonding material comprises: prior to the bonding, singulating the die into portions, wherein each portion of the die comprises at least one reaction site of the one or more reaction sites; and orienting the portions of the die on the first bonding material at a lateral distance from each other.

16. The method of claim 15, wherein placing the lidding layer over the surface comprises forming a stack, the method further comprising: modifying the stack by releasing the second carrier from the surface of the molding material; singulating the modified stack into packages, wherein each package comprises a given portion of the portions of the die; orienting at least one package on a substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the given portion of the die.

17. The method of claim 15, wherein placing the lidding layer over the surface comprises forming a stack, the method further comprising: singulating the stack into packages, wherein each package comprises a given portion of the portions of the die; orienting at least one package on a substrate such that the surface of the molding material is adjacent to an upper surface of the substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the given portion of the die.

18. A method comprising: forming die packages, comprising: depositing a first bonding material on a planar surface of a first carrier; bonding two or more dies to the first carrier, the bonding comprising orienting the two or more dies on the first bonding material such that the first bonding material bonds the two or more dies to the first carrier, wherein the orienting comprises placing the two or more dies on the planar surface at orientations wherein each die of the two or more dies is at a lateral distance from a next die of the two or more dies, wherein each die comprises one or more nanowells and one or more electrical contact points, wherein the nanowells are coupled to the first bonding material; encapsulating the two or more dies with a molding material, wherein portions of the molding material are flush to portions of the first bonding material; bonding a second carrier to a surface of the molding material with a second bonding material, wherein the planar surface of the first carrier and the surface of the molding material are parallel and separated by a longitudinal distance; rel easing the first carrier from the die encapsulated with the molding material to expose surfaces of the two or more dies comprising the nanowells and the portions of the molding material; and applying chemistry to surfaces of the two or more dies comprising the nanowells such that the surfaces of the two or more dies comprising the nanowells become active detection areas.

19. The method of claim 18, wherein forming the die packages further comprises: releasing the second carrier from the surface of the molding material; and dicing through the molding material to separate the two or more dies into individual die packages, wherein each die package comprises a die of the two or more dies and part of portions of the molding material comprising fanout regions on each side of the die of the two or more dies, and wherein a top surface of each die package comprises an active detection area of the active detection areas.

20. The method of claim 18 further comprising: dicing through the molding material and the second carrier to separate the two or more dies into individual die packages, wherein each die package comprises a die of the two or more dies and part of portions of the molding material comprising fanout regions on each side of the die of the two or more dies, and wherein a top surface of each die package comprises an active detection area of the active detection areas.

21. The method of claim 19 or claim 20, further comprising: orienting an individual die package of the individual die packages on a substrate, wherein the substrate comprises electrical contacts; and connecting the electrical contacts of the substrate to the electrical contact points of the individual die package.

22. The method of any one of claims 18-21, further comprising: singulating a die wafer to form the two or more dies.

23. The method of any one of claims 18-22, wherein the die wafer comprises a complementary metal-oxide semiconductor (CMOS).

24. The method of any one of claims 18-23, wherein the first carrier and the second carrier are each comprised of a material selected from the group consisting of: glass, quartz, silica, silicon, aluminum, and stainless steel.

25. The method of any one of claims 18-24, wherein the first bonding material and the second bonding material comprise a bonding tape.

26. The method of any one of claims 18-25, wherein releasing the first carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

27. The method of claim 19, wherein releasing the second carrier comprises applying thermal energy or ultraviolet radiation to the first bonding material.

28. The method of any one of claims 18-27, wherein the first carrier is transparent and wherein releasing the first carrier comprises applying heat or applying ultraviolet radiation to the first carrier.

29. The method of any one of claims 18-28, wherein the first carrier is not transparent and wherein releasing the first carrier comprises applying heat to the first carrier.

30. The method of claims 19, wherein the first carrier and the second carrier are transparent, wherein releasing the first carrier and releasing the second carrier comprise applying UV radiation to the first carrier and to the second carrier, and wherein a wavelength of UV radiation applied to release the first carrier is different than a wavelength of ultraviolet radiation applied to release the second carrier.

31. The method of claims 19, wherein releasing the first carrier comprises applying thermal energy to the first carrier, wherein releasing the second carrier comprises applying thermal energy to the second carrier, and wherein a temperature of the thermal energy applied for releasing the second carrier is greater than or equal to a temperature of the thermal energy applied for releasing the first carrier.

32. The method of any one of claims 18-31, wherein the molding material comprises epoxy mold compound.

33. The method of any one of claims 18-32, further comprising: planarizing the surface of the molding material parallel to the planar surface of the first carrier.

34. The method of any one of claims 18-33, wherein bonding the two or more dies to the first carrier comprises applying pressure to the first bonding material via the first carrier.

35. The method of any one of claims 18-34, wherein bonding the two or more dies to the second carrier comprises applying pressure to the second bonding material via the second carrier.

36. An apparatus comprising: a sensor package comprising a die encapsulated in a molding material, wherein a top surface of the sensor package comprises a detection surface of the die comprising one or more reaction sites and one or more electrical contact points, and portions of the molding material forming fanout areas at sidewalls of the die; a lidding layer over the detection surface oriented to define a fluidic channel over the detection surface, the lidding layer comprising an inlet and an outlet for fluid; and a carrier bonded to a bottom surface of the sensor package with a bonding material, wherein the bottom surface is parallel to the top surface.

37. The apparatus of claim 36, further comprising: a substrate comprising electrical contacts, the electrical contacts electrically coupled to the electrical contact points in the sensor package, wherein the substrate is bonded to the carrier.

38. A method comprising: placing one or more nucleic acids in reaction sites of a sensor in a flow cell, the flow cell comprising: a sensor package comprising a die encapsulated in a molding material, wherein a top surface of the sensor package comprises a detection surface of the die comprising one or more nanowells and one or more electrical contact points, and portions of the molding material forming fanout areas at sidewalls of the die, where the one or more nanowells comprise the reaction sites; a lidding layer over the detection surface oriented to define a fluidic channel over the detection surface, the lidding layer comprising an inlet and an outlet for fluid; a carrier bonded to a bottom surface of the sensor package with a bonding material, wherein the bottom surface is parallel to the top surface; and a substrate comprising electrical contacts, the electrical contacts electrically coupled to the electrical contact points in the sensor package, wherein the substrate is bonded to the carrier; exposing the reaction sites of the sensor package to light from a light source, wherein the light comprises excitation light and emitted light; and obtaining a signal from the sensor package.