Fluid flow channels above the active surface of the die

Abstract

The content provided herein includes various examples of devices, sensor systems, and examples of methods for manufacturing various aspects of devices and sensor systems. The method may include obtaining a tube core. One or more electrical contacts are accessible on the surface of the tube core. The method may also include forming an underfill layer in a cavity between the lower surface of the tube core and the substrate. The method may include forming a fluid fan-out region by depositing a curable material in a first space and a second space in the cavity. The method may also include forming a fluid flow channel above the active surface of the tube core.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 982,352, filed on February 27, 2020, entitled “FLUIDIC FLOW CHANNEL OVER ACTIVE SURFACE OF A DIE,” which is hereby incorporated by reference in its entirety for all purposes. Background Art

[0003] Various schemes in biological or chemical research involve carrying out controlled reactions. The specified reaction can then be observed or detected, and subsequent analysis can help identify or reveal the characteristics of the chemicals involved in the reaction. In some multiple determinations, an unknown analyte with an identifiable label (e.g., a fluorescent label) can be exposed to thousands of known probes under controlled conditions. Each known probe can be placed in a corresponding well of a microplate. Any chemical reaction occurring between the known probe and the unknown analyte in the observation well can help identify or reveal the characteristics of the analyte. Other examples of such schemes include known DNA sequencing processes, such as sequencing by synthesis (SBS) or cycle array sequencing.

[0004] In some fluorescence detection schemes, an optical system is used to direct excitation light to a fluorophore (e.g., a fluorescently labeled analyte), and is also used to detect fluorescence emission signal light that can be emitted from an analyte with a connected fluorophore. In other proposed detection systems, a controlled reaction in a circulation cell is detected by a solid-state light sensor array (e.g., a complementary metal oxide semiconductor (CMOS) detector). These systems do not involve large optical components for detecting fluorescence emission. The shape of the fluid flow channel in the circulation cell can determine its utility for various purposes, for example, using multiple liquid flows to implement SBS or cycle array sequencing in a sensor system, and therefore, a fluid flow channel of a specific shape is used for SBS or cycle array sequencing. Summary of the invention

[0005] Therefore, it may be advantageous to enable a flow cell manufacturing facility to manufacture and form flow cells on an individual level, i.e., using a process that can manufacture each tube core individually, rather than using an entire wafer to form multiple flow cells simultaneously, to control the formation of fluid flow channels above each individual tube core.

[0006] Therefore, the disadvantages of the prior art can be overcome, and the benefits described later in the present disclosure can be achieved by providing a method for manufacturing an apparatus for use in a sensor system. Various examples of the method are described below, and the method (including and excluding the additional examples listed below) overcomes these disadvantages in any combination (provided that these combinations are not inconsistent). The method includes: placing a die in a portion of a cavity in a substrate, wherein one or more electrical contacts on a surface of the die are accessible, wherein the substrate includes exposed electrical contacts accessible to the electrical contacts on the surface of the die, wherein the placement defines a first space in the cavity adjacent to a first edge of an upper surface of the die and a second space in the cavity adjacent to a second edge of the upper surface of the die; forming a bottom fill layer in the cavity between a lower surface of the die and the substrate; forming a fluid fan-out region by: depositing a curable material in the first space and the second space to form the fluid fan-out region, the surface of the fluid fan-out region being adjacent to the upper surface of the die; and forming a fluid flow channel above an active surface of the die, including: attaching a cap to a portion of the substrate adjacent to the fluid fan-out region to form a fluid flow channel between the active surface and the cap.

[0007] In some examples, the method also includes coupling the exposed electrical contacts to electrical contacts on the surface of the die.

[0008] In some examples of the method, the exposed electrical contacts and the electrical contacts on the surface of the die constitute bonding pads, including the bonding pads of the exposed electrical contacts each oriented in one of the first space or the second space, and the coupling includes wire bonding each of the exposed electrical contacts to one of the electrical contacts on the surface of the die to form a wire bonding connection.

[0009] In some examples, the method further includes encapsulating the wire bond connections by depositing a curable material over the fluid fan-out region prior to forming the fluid flow channel.

[0010] In some examples, forming the fluid flow channel over the active surface of the die further includes orienting the cap in physical contact with a top surface of each of the packaged wirebond connections, wherein the orientation flattens each top surface.

[0011] In some examples of the method, the die also includes one or more through silicon vias (TSVs) extending through a portion of the silicon wafer and a passivation stack disposed below a lower surface of the portion of the silicon wafer, a portion of each of the one or more TSVs being exposed through one of the one or more openings in the passivation stack, and each exposed portion being coupled to an electrical contact.

[0012] In some examples, placing also includes coupling the exposed electrical contacts to the electrical contacts.

[0013] In some examples, the method also includes coupling the exposed electrical contacts to electrical contacts on the surface of the die.

[0014] In some examples, the coupling includes utilizing a method selected from the group consisting of: reflowing the electrical contacts, wherein the electrical contacts of the die include stud bumps, and utilizing an anisotropic conductive film to couple the electrical contacts to the exposed electrical contacts.

[0015] In some examples of the method, the curable material is selected from the group consisting of epoxies and adhesives.

[0016] In some examples of the method, forming the fluid fan-out region further includes solidifying the curable material. The method further includes solidifying the curable material.

[0017] In some examples, the curing includes utilizing a method selected from the group consisting of: exposing the curable material to ultraviolet radiation and exposing the curable material to thermal energy.

[0018] In some examples of the method, the die includes a sensor.

[0019] In some examples of the method, the sensor includes a complementary metal oxide semiconductor (CMOS) detection device.

[0020] In some examples of the method, the cavity includes: a die cavity portion, a fluid cavity portion, and a top-level portion, wherein the die cavity portion and the bottom fill layer together have a height substantially equal to the die, wherein the fluid cavity portion includes a space having a height of a fluid flow channel, and wherein the top-level portion has a height of a portion of the substrate adjacent to the fluid fan-out region.

[0021] In some examples, placing the die in the portion of the cavity in the substrate includes placing the die in a die cavity portion of the substrate.

[0022] In some examples of the method, the portion of the substrate adjacent to the fluid fan-out region includes a portion of a circuit board, and the top-level portion includes an interface between the circuit board and the cover.

[0023] In some examples of the method, the cover includes an inlet for the fluid and an outlet for the fluid.

[0024] In some examples, attaching the cover includes applying an adhesive between the circuit board and the cover.

[0025] In some examples of the method, die are singulated from a silicon wafer.

[0026] In some examples of the method, the surface of the die is selected from: an upper surface of the die, a portion of the upper surface of the die including the active surface, and a lower surface parallel to the upper surface.

[0027] The disadvantages of the prior art can be overcome, and benefits as described later in the present disclosure can be achieved by providing an apparatus for use in a sensor system. Various examples of the apparatus are described below, and the apparatus (including and excluding the additional examples listed below) overcomes these disadvantages in any combination (provided that these combinations are not inconsistent). The apparatus includes: a die, wherein one or more electrical contacts on the surface of the die are accessible; a substrate, the substrate including a cavity, wherein the die is oriented in a portion of the cavity in the substrate, wherein the substrate includes exposed electrical contacts, which are electrically coupled to electrical contacts on the surface of the die, wherein the orientation defines a first space in the cavity adjacent to a first edge of the upper surface of the die and a second space in the cavity adjacent to a second edge of the upper surface of the die; and fluid fan-out regions, which include a first solidified material deposited in the first space and the second space, and the surfaces of the fluid fan-out regions are adjacent to the upper surface of the die.

[0028] In some examples of the device, the device also includes a fluid flow channel above the active surface of the tube core, the fluid flow channel being defined by a surface of the fluid fan-out area and an upper surface of the tube core and a cover attached to a portion of the substrate adjacent to the fluid fan-out area.

[0029] In some examples of the apparatus, the apparatus further includes an underfill layer in the cavity between the lower surface of the die and the substrate.

[0030] In some examples of the apparatus, the dies are singulated from a silicon wafer.

[0031] In some examples of the apparatus, the exposed electrical contacts constitute substrate bond pads and the electrical contacts on the surface of the die constitute die bond pads, and wherein each die bond pad is coupled to at least one substrate bond pad with a wire to form a wire bond connection.

[0032] In some examples of the apparatus, the wire bond connections are encapsulated in the second cured material.

[0033] In some examples of the apparatus, the cap is oriented to physically contact a top surface of each of the packaged wire bonded connections.

[0034] In some examples, the die also includes a silicon wafer, a passivation stack, and one or more through-silicon vias extending through a portion of the silicon wafer and the passivation stack, wherein the passivation stack is disposed below a lower surface of the portion of the silicon wafer, wherein a portion of each of the one or more through-silicon vias is exposed through one of the one or more openings in the passivation stack, and wherein each exposed portion is coupled to an electrical contact.

[0035] In some examples, the electrical contacts of the die include stud bumps.

[0036] In some examples, each of the curable material and the second curable material is selected from: an epoxy resin and an adhesive.

[0037] In some examples, the die includes a sensor.

[0038] In some examples, the sensor includes a complementary metal oxide semiconductor (CMOS) detection device.

[0039] In some examples of the device, the device also includes a bottom fill layer in the cavity between the lower surface of the tube core and the substrate, and the cavity includes: a tube core cavity portion, a fluid cavity portion, and a top portion, wherein the tube core cavity portion and the bottom fill layer have a height substantially equal to the tube core, wherein the fluid cavity portion includes a space having a height of the fluid flow channel, and wherein the top portion has a height of a portion of the substrate adjacent to the fluid fan-out area.

[0040] In some examples, the portion of the cavity in the substrate in which the die is oriented comprises the die cavity portion.

[0041] In some examples, the portion of the substrate adjacent to the fluid fan-out region includes a portion of a circuit board, and the top-level portion includes an interface between the circuit board and the cover.

[0042] In some examples, the cover includes an inlet for the fluid and an outlet for the fluid.

[0043] In some examples, the fluid flow channel is approximately 100 μm from the active surface to the cover.

[0044] In some examples, the circuit board is selected from: a printed circuit board and a ceramic circuit board.

[0045] In some examples, the surface is selected from: an upper surface of the die, a portion of the upper surface of the die including the active surface, and a lower surface parallel to the upper surface.

[0046] Thus, the disadvantages of the prior art can be overcome, and the benefits as described later in the present disclosure can be achieved by providing a method for manufacturing a device for use in a sensor system. Various examples of the method are described below, and the method (including and excluding the additional examples listed below) overcomes these disadvantages in any combination (provided that these combinations are not inconsistent). The method includes: picking up and placing a die including a sensor and one or more electrical contacts accessible on the surface of the die on a cavity surface at the base of a cavity of a carrier, wherein the carrier includes a substrate and a cavity, wherein the substrate includes exposed electrical contacts, and wherein the placement defines a first space in the cavity adjacent to a first edge of the surface of the die and a second space in the cavity adjacent to a second edge of the surface of the die; connecting each of the one or more electrical contacts of the die to at least one of the exposed electrical contacts of the substrate; forming a fluid fan-out region by: depositing a curable material in the first space and the second space to form a fluid fan-out region; and attaching a cap to a portion of the substrate adjacent to the fluid fan-out region to form a fluid flow channel between the active surface of the sensor and the cap.

[0047] In some examples of the method, the electrical contacts of the die include stud bumps.

[0048] The disadvantages of the prior art can be overcome, and the benefits as described later in the present disclosure can be achieved by providing a device for use in a sensor system. Various examples of the device are described below, and the device (including and excluding the additional examples listed below) overcomes these disadvantages in any combination (provided that these combinations are not inconsistent). The device includes: a tube core; a substrate, the substrate includes a cavity, wherein the tube core is oriented in a portion of the cavity in the substrate, wherein the orientation defines a first space in the cavity adjacent to a first edge of the upper surface of the tube core and a second space in the cavity adjacent to a second edge of the upper surface of the tube core; fluid fan-out areas, these fluid fan-out areas include a first solidified material deposited in the first space and the second space, and the surfaces of these fluid fan-out areas are adjacent to the upper surface of the tube core; and a fluid flow channel above the active surface of the tube core, the fluid flow channel is defined by the surface of the fluid fan-out area and the upper surface of the tube core and a cover attached to the portion of the substrate adjacent to the fluid fan-out area.

[0049] Additional features are achieved through the techniques described herein. Other examples and aspects are described in detail herein and are considered part of the aspects protected by the claims. These and other objects, features and advantages of the present disclosure will become apparent from the following detailed description of the various aspects of the present disclosure in conjunction with the accompanying drawings.

[0050] 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 present subject matter and achieve the advantages disclosed herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] One or more aspects are particularly pointed out and distinctly claimed as examples in the claims at the end of this specification. The foregoing contents and objects, features and advantages of one or more aspects will be apparent from the following detailed description taken in conjunction with the accompanying drawings, in which:

[0052] Figure 1 An example of a flow cell is depicted, the flow cell comprising a substrate having a cavity in which a sensor is positioned;

[0053] Figure 2 An example of a flow cell is depicted, the flow cell comprising a substrate having a cavity in which a sensor is positioned;

[0054] Figure 3 An example of a flow cell is depicted, the flow cell comprising a substrate having a cavity in which a sensor is positioned;

[0055] Figure 4 An example of a flow cell is depicted, the flow cell comprising a substrate having a cavity in which a sensor is positioned;

[0056] Figure 5 Depicted is an exemplary workflow showing the manufacturing Figures 1 to 4 Any flow cell process;

[0057] FIG. 6A to FIG. 6C Various views of a substrate having one or more pre-designed cavities in one example are depicted, such that the substrate can be used to manufacture Figure 1 In the method of the flow cell;

[0058] 7A to 7E Depicted is an example of a method for manufacturing Figure 1 The flow cell process at different points FIG. 6A to FIG. 6C A cross section of a substrate;

[0059] FIG. 8A to FIG. 8C Depicts an example of using Figure 5 and 7A to 7E Various views of an example of a flow cell fabricated by the method shown;

[0060] 9A to 9C Various views of a substrate having one or more pre-designed cavities in one example are depicted, such that the substrate can be used to manufacture Figure 2 In the method of the flow cell;

[0061] FIG. 10A to FIG. 10EDepicted is an example of a method for manufacturing Figure 2 The flow cell process at different points 9A to 9C A cross section of a substrate;

[0062] FIG. 11A to FIG. 11C Describes the use of Figure 5 and FIG. 10A to FIG. 10E Various views of an example of a flow cell fabricated by the method shown;

[0063] FIG. 12A to FIG. 12C Various views of a substrate having one or more pre-designed cavities in one example are depicted, such that the substrate can be used to manufacture Figure 3 In the method of the flow cell;

[0064] FIG. 13A to FIG. 13F Depicted is an example of a method for manufacturing Figure 3 The flow cell process at different points FIG. 12A to FIG. 12C A cross section of a substrate;

[0065] FIG. 14A to FIG. 14C Describes the use of Figure 5 and FIG. 13A to FIG. 13F Various views of an example of a flow cell fabricated by the method shown;

[0066] FIG. 15A to FIG. 15C Various views of a substrate having one or more pre-designed cavities in one example are depicted, such that the substrate can be used to manufacture Figure 4 In the method of the flow cell;

[0067] FIG. 16A to FIG. 16F Depicted is an example of a method for manufacturing Figure 4 The flow cell process at different points FIG. 15A to FIG. 15C A cross section of a substrate;

[0068] FIG. 17A to FIG. 17C Depicts an example of using Figure 5 and FIG. 16A to FIG. 16F Various views of an example of a flow cell fabricated by the method shown;

[0069] 18A to 18C depicts various views of an example of a flow cell in which a carrier including a substrate includes cavities for individually housing a plurality of silicon CMOS sensors;

[0070] Fig.19 depicts an example of a flow cell where thermal management is accomplished by adding thermal vias; and

[0071] FIG. 20A to FIG. 20B Depicted are examples of flow cells where thermal management is accomplished by adding through cuts to the substrate or by adding additional cavities in the substrate. DETAILED DESCRIPTION

[0072] The accompanying drawings further illustrate embodiments of the present invention and, together with the detailed description of the embodiments, are used to explain the principles of the embodiments of the present invention, in which like reference numerals refer to the same or functionally similar elements throughout the individual views, and the accompanying drawings are incorporated in and form a part of this specification. As will be appreciated by those skilled in the art, the accompanying drawings are provided to facilitate understanding and illustrate various aspects of certain examples of embodiments of the present invention. The embodiments are not limited to the examples depicted in the accompanying drawings.

[0073] The terms "connected," "connected," "contacted," "coupled," and the like are broadly defined herein to encompass a variety of discrete arrangements and assembly techniques. These arrangements and techniques include, but are not limited to: (1) the direct engagement of one component with another component without intervening components (i.e., the components are in direct physical contact); and (2) the engagement of one component with another component with one or more components in between, provided that the one component is "connected to" or "contacted with" or "coupled to" the other component to some extent in operational communication (e.g., electrical, fluidic, physical, optical communication, etc.) with the other component (although there are one or more additional components in between). It should be understood that some components that are in direct physical contact with each other may or may not be in electrical and / or fluidic contact with each other. In addition, two components that are electrically connected, electrically coupled, optically connected, optically coupled, fluidically connected, or fluidically coupled may or may not be in direct physical contact, and one or more other components may be disposed between the two components.

[0074] As used herein, the terms "including" and "comprising" are synonymous.

[0075] 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 illustrate small fluctuations from a reference or parameter, for example, due to changes in processing. Such small fluctuations also include zero fluctuations from a reference or parameter. For example, they may 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, i.e., ±0%.

[0076] As used herein, "circulation cell" may include a device with a cap extending above the reaction structure to form a flow channel communicating with multiple reaction sites of the reaction structure therebetween, and may include a detection device for detecting a specified reaction occurring at or near the reaction site. The circulation cell may include a solid-state light detection or "imaging" device, such as a charge coupled device (CCD) or a complementary metal oxide semiconductor (CMOS) (light) detection device. As a specific example, the circulation cell may be fluidically coupled and electrically coupled to a box (with an integrated pump), which may be fluidically coupled and / or electrically coupled to a bioassay system. The box and / or the bioassay system may deliver the reaction solution to the reaction site of the circulation cell according to a predetermined scheme (e.g., sequencing while synthesizing), and perform multiple imaging events. For example, the box and / or the bioassay system may guide one or more reaction solutions through the flow channel of the circulation cell, thereby flowing along the reaction site. At least one of the reaction solutions may include four types of nucleotides with the same or different fluorescent labels. In some examples, the nucleotides are bound to the reaction site of the circulation cell, such as the corresponding oligonucleotides bound to the reaction site. The cartridge and / or bioassay system in these examples then illuminates the reaction site using an excitation light source (e.g., a solid-state light source, such as a light emitting diode (LED)). In some examples, the excitation light has one or more predetermined wavelengths, including a range of wavelengths. The fluorescent markers excited by the incident excitation light can provide an emission signal (e.g., light of one or more wavelengths that are different from the excitation light and may be different from each other) that can be detected by the light sensor of the flow cell.

[0077] Flow cell as described herein performs various biological or chemical processes. More specifically, flow cell as described herein can be used for various processes and systems in which it is desired to detect events, attributes, quality or features indicating a specified reaction. For example, flow cell as described herein can include light detection equipment, sensors (including but not limited to biosensors and parts thereof), and bioassay systems operated with sensors (including biosensors), or integrated with the aforementioned equipment.

[0078] The circulation cell promotes multiple specified reactions that can be detected individually or together. The circulation cell performs multiple cycles, wherein the multiple specified reactions occur in parallel. For example, the circulation cell can be used to sequence a dense array of DNA features through iterative cycles of enzyme manipulation and light or image detection / collection. Therefore, the circulation cell can be in fluid communication with one or more microfluidic channels, and the microfluidic channels deliver reagents or other reaction components in the reaction solution to the reaction sites of the circulation cell. The reaction sites can be provided or spaced apart in a predetermined manner, such as provided or spaced apart in a uniform or repeated pattern. Alternatively, the reaction sites can be randomly distributed. Each site in the reaction site can 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, the light guide includes one or more filters for filtering light of certain wavelengths. The light guide can be, for example, an absorption filter (e.g., an organic absorption filter) so that the filter material absorbs a specific wavelength (or wavelength range) and allows at least one predetermined wavelength (or wavelength range) to pass therethrough. In some circulation cells, the reaction site can be located in a reaction groove or reaction chamber, which can at least partially separate the specified reactions therein.

[0079] As used herein, a "specified reaction" includes a change in at least one of the chemical, electrical, physical, or optical properties (or mass) of a chemical or biological substance of interest (e.g., an analyte of interest). In a particular flow cell, the specified reaction is a positive binding event, for example, the binding of a fluorescently labeled biomolecule to an analyte of interest. More generally, a specified reaction can be a chemical transformation, a chemical change, or a chemical interaction. A specified reaction can also be a change in an electrical property. In a particular flow cell, a specified reaction includes binding a fluorescently labeled molecule to an analyte. The analyte can be an oligonucleotide, and the fluorescently labeled molecule can be a nucleotide. A specified reaction can be detected when excitation light is directed to an oligonucleotide having a labeled nucleotide and the fluorophore emits a detectable fluorescent signal. In another example of a flow cell, the detected fluorescence is the result of chemiluminescence or bioluminescence. A specified reaction can also be, for example, to increase fluorescence (or ) resonance energy transfer (FRET), reducing FRET by separating the donor and acceptor fluorophores, increasing fluorescence by separating the quencher from the fluorophore, or decreasing fluorescence by colocalizing the quencher and fluorophore.

[0080] As used herein, "electrically coupled" and "optically coupled" refer to the transfer of electrical energy and light waves, respectively, between any combination of power sources, electrodes, conductive portions of substrates, droplets, conductive traces, wires, waveguides, nanostructures, other circuit segments, etc. The terms "electrically coupled" and "optically coupled" may be used in conjunction with direct or indirect connections, and may be through various intermediaries, such as fluid intermediaries, air gaps, etc.

[0081] As used herein, "reaction solution," "reaction component," or "reactant" includes any substance that can be used to obtain at least one specified reaction. For example, possible reaction components include, for example, reagents, enzymes, samples, other biomolecules, and buffers. The reaction components can be delivered to and / or fixed at the reaction sites in the flow cells disclosed herein. The reaction components can interact directly or indirectly with another substance, such as an analyte of interest fixed at the reaction site of the flow cell.

[0082] As used herein, the term "reaction site" is a local area where at least one specified reaction can occur. The reaction site can include a reaction structure or a support surface of a substrate on which a substance can be fixed. For example, the reaction site can include a surface (can be located in a channel of a circulation cell) of a reaction structure with a reactive component (such as a nucleic acid colony thereon). In some circulation cells, the nucleic acid in the colony has the same sequence, for example, a cloned copy of a strand or double-stranded template. However, in some circulation cells, the reaction site can only include a single nucleic acid molecule, such as a strand or double-stranded form.

[0083] The term "fan-out" is used herein to characterize the area packaged with the detector that extends beyond the horizontal distance of the detector. For example, in the example where a CMOS sensor is used as a detector in a flow cell, the fan-out refers to the additional horizontal distance on each side of the horizontal boundary of the CMOS sensor.

[0084] As used herein, the term "pillar bump" is used to describe the electrical contacts in the examples shown and described herein. In the various examples of the devices shown herein, various examples of electrical contacts may also be used wherever the term "pillar bump" is used. The electrical contact, which may be a pillar bump, may include a conductive material, such as a metallic material (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum), or a combination thereof), but it should be understood that other conductive materials may be utilized.

[0085] Reference will now be made to the drawings, which are not drawn to scale for ease of understanding, and in which the same reference numerals are used throughout the different drawings to designate the same or similar components.

[0086] Detection devices and image sensors that can be used as sensors (such as biosensors) in flow cells include image sensors or detectors that contain a CMOS and a fan-out region. The surface of the CMOS and the fan-out region (on either side) form an active surface. In a CMOS (e.g., Figure 1Above the active surface of the silicon wafer 130 in the flow cell 100 is a (micro) fluid flow channel, which is defined by the cap and adjacent surface of the flow cell 100 on one side, and the adjacent surface includes the active surface of the silicon wafer and the portion of the fan-out area on either side of the surface of the silicon wafer. When manufacturing the flow cell, one or more molding processes in a variety of complex molding processes can be used to form the fluid flow channel above the CMOS or other sensor, and the various complex molding processes involve a manufacturing technology consisting of multiple processes, each of which may or may not bring inconsistencies. In addition, various factors in the manufacture and / or construction of the system can affect the effectiveness of the system. For example, the engagement of the cap with the sensor surface can result in improper coverage of the pixel area, thereby reducing the total number of pixels available. Another example of a channel shape that may not be used for SBS is a channel between the cap and the CMOS, which is not designed to achieve uniform fluid flow above the sensing area (e.g., active surface). If the fluid flow channel is not formed in a usable shape, the reagents are not exchanged (e.g., single-pot reagents) or cannot be exchanged in a way that provides reliable results. Therefore, it is expected that any manufacturing process of the flow cell includes fewer processes and / or a less complex molding process, but the resulting flow cell includes fluid flow channels that can be used with biosensor processes (including but not limited to SBS or cycle array sequencing).

[0087] To this end, examples discussed herein include methods (and resulting devices) that provide yield improvement by including a designed cavity-based substrate in the formation or manufacture of a flow cell. In the examples discussed herein, the cavity-based substrate encapsulates a molding compound and a die to form a sensor system.

[0088] In some examples, a sensor system including a fan-out region and a flow channel is provided, in part, by molding on a cavity-based substrate. In some examples, a fluid flow channel having material compatibility with sequencing is formed over a separate die (e.g., a sensor) without utilizing a complex molding process in existing methods. A material is compatible when the material used to form the fluid path is chemically and biochemically compatible with the sequencing reagents and enzymes. For example, a material is compatible when the enzymatic activity in one of the reagents is not inhibited by contact with the material of the flow channel.

[0089] Figures 1 to 4 Examples of sensor systems that can be formed using examples of the methods discussed herein are shown. Various processes for forming these sensor systems are discussed, but Figures 1 to 4 It is to illustrate some examples of the resulting devices. Figures 1 to 4 are all cross-sectional views of examples of sensor systems. Figure 1 to Figure 2Both depict examples of flow cells having one or more TSVs 120 passing through a silicon wafer 130 to enable heat transfer from the silicon wafer 130 (eg, CMOS). Figure 3 to Figure 4 An example of a sensor system formed as a result of an example of the method disclosed herein is depicted in which TSVs are not used for heat transfer.

[0090] Figure 1 An example of a flow cell 100 (also referred to herein as a "sensor system") formed using some of the methods described herein is provided. Figure 1 In the flow cell 100, a portion is formed by joining a sensor structure 142 to a carrier 196 including a substrate 197. The carrier includes at least one cavity 105, the bottom of the cavity includes the substrate 197, and the sensor structure 142 is placed in the cavity 105. The cavity 105 can be understood to include different parts that will be discussed herein, including a sensor structure cavity portion 109 (which can also be understood as a tube core cavity portion) and a fluid flow channel portion 111 in some examples (which can also be understood as a fluid cavity portion). The placement of the sensor structure 142 in the cavity 105 is discussed in various examples herein.

[0091] like Figure 1 As shown in the example of FIG. 1 , the sensor structure 142 portion of the flow cell 100 includes an active (photosensitive) surface 110 of a silicon wafer die 130 (e.g., CMOS) for light-sensing activities (e.g., DNA sequencing). A chemical coating (not shown) may have been previously applied to the active surface 110. Above the active surface 110 of the silicon wafer die 130 including the chemical coating (not shown) is a (micro)fluidic flow channel 192, which is defined by a cap 190 of the flow cell 100 on one side and an adjacent surface, which includes the active surface 110 of the silicon wafer die 130 and portions of the fan-out region 180 on either side of the surface of the silicon wafer die 130. As depicted in the example, the cap 190 is attached to a carrier 196. Capping the carrier 196 (rather than the active surface 110 and / or the fan-out region 180 adjacent to the active surface 110) can avoid area loss when utilizing the flow cell in its sensor system utility.

[0092] In this example, the (micro)fluid flow channel 192 is further defined by a portion of the carrier 196. In this example, the vertical height of the carrier 196 wall 103 adjacent to the cavity 105 containing the sensor structure 142 exceeds the vertical height of the sensor structure 142 when placed in the cavity 105. For example, a cover 190 (e.g., a glass or other translucent cover) may or may not be attached to the carrier wall 103 at the upper surface of each wall 103 by applying an adhesive to the cover 190 and the carrier 196. When the silicon wafer die 130 is used as a digital image sensor, the active surface 110 of the digital image sensor includes photosites or pixels for sensing light. In these examples, non-limiting examples of sensor functions include, for example, light sensing (e.g., having a predetermined wavelength range sensed), detecting the presence of one or more substances (e.g., biological or chemical substances), and detecting changes in the concentration of something (e.g., ion concentration).

[0093] exist Figure 1 In the example shown, the sensor structure 142 also includes one or more TSVs 120 that pass through the silicon wafer die 130 to at least a passivation layer 140 on one or more backside metallization layers, which in some examples are metallization layers for RDL. In some examples, the passivation layer 140 is a polyamide layer deposited and cured at a relatively high temperature (e.g., about 100° C.-180° C.). Connection to the TSVs 120 and therefore to the silicon wafer die 130 is facilitated by an opening area 150 in the passivation layer 140. For ease of understanding, the passivation layer 140 is formed at a substantially flat surface. Figure 1140 is depicted as a separate layer in the figure. However, the passivation layer 140 is part of the silicon wafer die 130 (and the sensor structure 142), and even if it exists, it is not illustrated as a separate layer in all the figures herein, so as to depict the silicon wafer die 130 (and the sensor structure 142) in a simpler manner. These opening areas are used to form an electrical connection with the passivation layer 140 to form a pad 160. Electrical contacts, commonly referred to as column bumps 170 or column bumps, are formed on the pad 160. The column bump 170 may include any suitable material, including a conductive material. For example, the column bump 170 may include a conductive material, such as a metallic material (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum) or a combination thereof), but it should be understood that other conductive materials may be used. In a specific implementation, the metal (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum) or a combination thereof) may be an element, an alloy, or a composite material containing a metal. It is noted that although the term "copper pillar bump" is used, copper is used only as a demonstration material for the pillar bump, and the pillar bump need not consist of or include copper. Connection to the pillar bump 170 is provided by reaching through the underfill layer 173 to the electrical connection 175 embedded in the substrate 197 portion of the carrier 196. In this example, the sensor structure 142 also includes a fan-out region 180, which can be formed of a material including but not limited to an adhesive and / or epoxy resin that can be cured by methods including but not limited to UV exposure and / or thermal exposure, as described in the examples herein.

[0094] Figure 1 The substrate 197 of the example in may include at least one RDL or other passivation layer 182 (e.g., polyamide). An opening is formed in the RDL or other passivation layer 182 to provide access to the pillar bump 170 (for electrical connection). In this example, on the substrate 197, another passivation layer 182 (e.g., polyamide, epoxy resin, solder resist, etc.) deposited on the RDL or other passivation layer 182 protects the RDL or other passivation layer 182, increases reliability, and reduces and in some cases even prevents electrical shorts. The opening in the other passivation layer is electrically connected to the RDL or other passivation layer 182 (the passivation layer 182 below the bottom filler 173) via the electrical contact 175.

[0095] Figure 2 is an example of a flow cell having one or more TSVs 220, but including a carrier 296 of a substrate 297 and Figure 1 The example shown is different because when the sensor structure 242 is placed in the cavity 205 of the carrier 296, the wall 203 of the carrier 296 is the same height as the sensor structure 242, and there is an underfill layer between the carrier 296 and the sensor structure 242. Figure 2The cavity 205 in the carrier 296 cannot provide the horizontal limit of the substrate 297 and the (micro) fluid flow channel 292 at the same time. The cavity 205 includes the sensor structure cavity part 209 (which can also be understood as the tube core cavity part) but does not include the fluid flow channel part. Figure 2 , in this example, the (micro) fluid flow channel 292 is partially formed by a high structure 277, which in this example is a structure added above the top surface of the wall 203 of the carrier 296. The use of the high structure 277 to form the (micro) fluid flow channel 292 will be explained in more detail herein.

[0096] like Figure 1 Described in Figure 2 , a flow cell 200 is formed in part by combining a sensor structure 242 with a carrier 296 including a substrate 297. The flow cell 200 includes an active (photosensitive) surface 210 of a silicon wafer die 230 (e.g., CMOS) for light-sensitive activities (e.g., DNA sequencing). A chemical coating (not shown) may have been previously applied to the active surface 210. Above the active surface 210 of the silicon wafer die 230 is the above-mentioned (micro)fluidic flow channel 292, which is defined by a cover 290 (e.g., a glass or other translucent cover) of the flow cell 200 on one side and an adjacent surface, which includes the active surface 210 of the silicon wafer die 230 and portions of a fan-out region 280 on either side of that surface of the silicon wafer die 230. As depicted in this example, the cap 290 is attached to the tall structure 277, which is a structure that extends the vertical height of the wall 203 of the carrier 292 to exceed the vertical height of the sensor structure 242 when located in the cavity 205. The space that is the height difference between the height of the sensor structure 242 and the tall structure 277 (reaching the cap 290 across the active surface 210 of the silicon wafer die 230 and the portion of the fan-out area 280 on either side of this surface of the silicon wafer die 230) forms the (micro) fluid flow channel 292. The cap 290 is attached to the top surface of the tall structure 277. Figure 1 As in , in this example, capping the tall structures 277 (rather than the active surface 210 and / or the fan-out region 280 adjacent to the active surface 210) may avoid area loss when utilizing the flow cell in its sensor system utility.

[0097] exist Figure 2 In the example shown, the sensor structure 242 includes one or more TSVs 220 that pass through the silicon wafer die 230 to at least a passivation layer 240 on one or more backside metallization layers, which in some examples are metallization layers that are RDLs. Figure 1As in FIG. 1 , connection to TSV 220 and thus to silicon wafer die 230 is facilitated by opening region 250 in passivation layer 240. For ease of understanding, passivation layer 240 is Figure 2 297. However, the passivation layer 240 is part of the silicon wafer die 230 (and the sensor structure 242), and even if present, is not illustrated as a separate layer in all the figures herein in order to depict the silicon wafer die 230 (and the sensor structure 242) in a simpler manner. These opening areas are used to form an electrical connection with the passivation layer 240 to form a pad 260. Electrical contacts, commonly referred to as column bumps 270 or column bumps, are formed on the pad 260. Connection to the column bump 270 is provided by passing through the bottom fill layer 273 to reach the electrical connection 275 embedded in the substrate 297. In this example, the sensor structure 242 also includes a fan-out region 280, which, as described in the examples herein, can be formed of a material including but not limited to an adhesive and / or epoxy resin that can be cured by methods including but not limited to UV exposure and / or heat exposure.

[0098] Figure 2 The substrate 297 of the example in may also include at least one RDL or other passivation layer 282 (e.g., polyamide). An opening is formed in the RDL or other passivation layer 282 to provide access to the pillar bump 270 (for electrical connection). In this example, on the substrate 297, another passivation layer 182 (e.g., polyamide, epoxy resin, solder resist, etc.) deposited on the RDL or other passivation layer 284 protects the RDL or other passivation layer 282, increases reliability, and reduces and in some cases even prevents electrical shorts. The opening 286 in the other passivation layer 282 is electrically connected to the RDL or other passivation layer 282 (the passivation layer 282 below the bottom filler 273) via the electrical contact 275.

[0099] With the above Figure 1 to Figure 2 Same, Figure 3 to Figure 4 300, 400 are formed without TSVs that provide heat transfer from silicon wafers 330, 420 (e.g., CMOS). In both flow cells 300, 400, wire bonds 331, 431 are formed to electrically connect silicon wafer dies 330, 430 (e.g., sensors) to carriers 397, 497 including substrates 396, 496, but the placement of the connected portions on carriers 397, 497 is different based on the shape of the one or more cavities and / or portions of the cavities in each carrier 397, 497.

[0100] Now go to Figure 3Once the sensor structure is placed on top of the bottom fill layer 373, a portion of the cavity 305 in the carrier 397 that houses the sensor structure 342 is the same vertical height as the sensor structure 342. The fan-out regions 380 on either side of the sensor structure 342 and the sensor structure 342 itself (the sensor structure having an upper surface that is an abutting surface that includes the active surface 310 of the silicon wafer die 330 and portions of the fan-out regions 380 on either side of that surface of the silicon wafer die 330) fill that portion of the cavity 305. This portion of the cavity can be understood to include the sensor structure cavity portion 309 (which can also be understood to be a die cavity portion). Attached to the portion of the fan-out region 380 are the bonding pads 337. Thus, these bonding pads are formed on the top surface of the silicon wafer die 330. With Figure 1 to Figure 2 As in FIG. 1 , the sensor structure 342 is placed on the bottom filler 373 in the cavity 305, which acts as a transition layer between the sensor structure 342 and the substrate 397. The silicon wafer die 330 (and the sensor structure 342) includes a passivation layer 340, which is formed at the bottom of the cavity 305. Figure 3 The passivation layer 340, even if present, is not illustrated as a separate layer in all figures herein in order to depict the silicon wafer die 330 (and the sensor structure 342) in a simpler manner.

[0101] exist Figure 3 396. In the example depicted in FIG. 390 , the sensor structure 342 is electrically connected to the topside substrate bonding pads 341 on the carrier 396. Each topside substrate bonding pad 341 (at least one on each side of the portion of the cavity 305 that accommodates the sensor structure 342) resides in a portion of the cavity 305 in the carrier 396 that begins at the vertical height of the sensor structure 342 near the fan-out region 380 on each side, but extends horizontally toward the wall 303 of the cavity 305 in the carrier 396. As further shown in the discussion of methods and other examples of forming the flow cell 300, the horizontal space on each side of the cavity 305 is large enough to accommodate the topside substrate bonding pads 341. In the flow cell 300, bonding wires 331 are formed to electrically connect the silicon wafer die 330 (e.g., a sensor) to the carrier 397 including the substrate 396. These bonding wires 331 connect bonding pads 337 on the top surface of the silicon wafer die 330 to the topside substrate bonding pads 341. In this example, the bonding pads 337 on the top surface of the silicon wafer die 330 are connected to the electrical vias 346. Some examples (not shown) do not include these electrical vias 346. Figure 3396, but in some flow cells, for example, these top side substrate bonding pads 341 are electrically connected to the bottom substrate bonding pads through a single through hole or alternatively through several through holes that extend through multiple metal layers of the substrate 396. The bonding wires can be composed of one or more metals such as aluminum, copper, silver, gold, or any combination thereof. The metal in the bonding wire can be in elemental form, alloy form, or composite form. For example, the wire bonding can include, for example, forming a eutectic metal bond.

[0102] exist Figure 3 305, the bonding wires 331, bonding pads 337, and top side substrate bonding pads 341 connecting bonding pads 337 on the top surface of silicon wafer die 330 are encapsulated. The material used to encapsulate the connection may or may not be the same filler material as used to form fan-out region 380. The encapsulation of the connection extends above the portion of fan-out region 380 on which bonding pads 337 are formed to a vertical height close to the vertical height of the wall 303 of carrier 396 that defines the horizontal boundary of the entire cavity 305. The (micro) fluid flow channel 392 is defined by the cover 390 of the flow cell 300 on one side, a portion of the adjacent surface (excluding the portion with the encapsulated connection 328) (including the active surface 310 of the silicon wafer die 330), and the encapsulation 328 of the connection. As will be discussed herein, the (micro) fluid flow channel 392 is also partially defined by the fluid flow channel portion 311 (which can also be understood as a fluid cavity portion) and the wire bond encapsulation portion 324 of the cavity 305. The top surface of the carrier 396 and the package 328 interface with the cover 390. In the horizontal direction, the (micro)fluidic flow channel 392 is bounded by the cover 390 and the active surface 310.

[0103] Now go to Figure 4 ,and Figure 1 Like the carrier in FIG. 4 , the carrier 496 includes a single cavity 405 in which the sensor structure 442 is placed, and the bottom filler 473 forms an interface between the bottom surface of the sensor structure 442 and the top surface of the cavity 405 of the substrate 497. Figure 3 The sensor structure 342 is the same as that of Figure 4 The sensor structure includes a bonding pad 437 on a silicon wafer die 430. Figures 1 to 3 As with the silicon wafer die 430, the silicon wafer die 430 is first singulated from the wafer and then placed in the cavity 405. As will be discussed herein, the cavity comprises two parts, the sensor structure 442 being positioned in the sensor structure cavity portion 409 (which may also be understood as the die cavity portion), and the fluid flow channel portion of the cavity 405 defining a portion of the (micro) fluid flow channel 492. Figure 3Unlike in the flow cell 400, the top side substrate bonding pads 441 (on which the bonding pads 437 on the silicon wafer die 430 are positioned) are near the outer edge of the cavity 405 in which the sensor structure 442 is placed (the sensor structure 442 is relatively centered in the cavity 405). In this flow cell 400, wire bonds 431 are formed to electrically connect the silicon wafer die 430 (e.g., sensor) to a carrier 497 including a substrate 496. These wire bonds 431 connect the bonding pads 437 on the top surface of the silicon wafer die 430 to the top side substrate bonding pads 441 in the same portion of the cavity 405 (e.g., the sensor structure cavity portion 409). The connections including the wire bonds 431, the bonding pads 437, and the top side substrate bonding pads 441 are packaged to form fillers on each side of the sensor structure 442 to the areas of the walls 403 of the carrier 496 that form the sides of the cavity 405. The encapsulation of the connection 428 extends approximately to the vertical height of the wall 403 and above the sensor structure 442, covering at least a portion of the fan-out area 480 on each side of the silicon wafer die 430 in order to encapsulate the bonding pads 437. The (micro) fluid flow channel 492 is defined by the cover 490 of the flow cell 400 on one side, a portion of the adjacent surface (excluding the portion with the encapsulated connection) (including the active surface 410 of the silicon wafer die 430) and the encapsulation 428 of the connection. The top surface of the carrier 496 and the encapsulation 428 interface with the cover 490. In the horizontal direction, the (micro) fluid flow channel 492 is defined by the cover 490 and the active surface 410. The silicon wafer die 430 (and the sensor structure 442) includes a passivation layer 340, which is formed at the bottom of the passivation layer 340. Figure 3 The passivation layer 440, even if present, is not illustrated as a separate layer in all figures herein in order to depict the silicon wafer die 430 (and the sensor structure 442) in a simpler manner.

[0104] Figure 5 is a workflow 500 showing the formation of a flow cell (such as a flow cell) in part by combining a carrier having a cavity 405 (the carrier comprising a substrate) with a sensor structure comprising a die. Figures 1 to 4 Certain aspects of some of the examples disclosed herein (such as those depicted in Figure 5 As shown, for example, the method may include obtaining a die (ie, sensor system 142, 242, 342, 442) wherein one or more electrical contacts on a surface of the die are accessible (510). Figures 1 to 4 As shown, the electrical contacts on the die may be located on different portions of the die, including but not limited to the upper surface of the die, a portion of the upper surface of the die including the active surface, and / or a lower surface parallel to the upper surface. Figure 5As shown, the method may also include placing the tube core in a portion of a cavity 405 in a carrier including a substrate, wherein the substrate includes exposed electrical contacts accessible to electrical contacts on a surface of the tube core, such that the placement is capable of coupling the exposed electrical contacts to electrical contacts on the surface of the tube core, and the placement defines a first space in the cavity adjacent to a first edge of the upper surface of the tube core and a second space in the cavity adjacent to a second edge of the upper surface of the tube core (520).

[0105] like Figures 1 to 4 As shown, the bottom filler 173, 273, 373, 473 may form an interface between the sensor structure 142, 242, 342, 442 and the bottom of the substrate cavity 105, 205, 305, 405, so that Figure 5 The method includes forming a bottom fill layer in a cavity between a lower surface of the die and a substrate (530). The method also includes forming fan-out regions, for example by depositing a curable material in a first space and a second space to form fan-out regions, the surfaces of which are adjacent to an upper surface of the die (540). As discussed above, forming a fluid flow channel enables the flow cell to be utilized for various purposes, so the method includes forming a fluid flow channel above an active surface of the die, which includes attaching a cap to a portion of the carrier adjacent to the fan-out region to form a fluid flow channel between the active surface and the cap (550).

[0106] Considering Figure 5 The general workflow of 500, 6A to 8C Shown in more detail Figure 1 Examples of various aspects of the formation of the flow cell 100.

[0107] See also FIG. 6A to FIG. 6C , Fig. 6A Yes also Figure 1 696, which includes a substrate 697. Once the flow cell 100 ( Figure 1 ), the cavity 605 in the carrier 696 has different sections of different depths (heights) for different purposes. One section of the cavity 605 (i.e., the sensor structure cavity portion 609 (which can also be understood as the tube core cavity portion)) is approximately and in some cases exactly the vertical height of the sensor structure (the height is the height after the sensor structure is picked up and placed in the cavity 605 on the bottom filler + / - standard tolerance; examples of standard tolerances compatible with the example shown are about + / -3μm and θ is about + / -0.07 degrees). The second section (i.e., the fluid flow channel portion 611 (which can also be understood as the fluid cavity portion)) starts at the top of the sensor structure cavity portion 609 and defines the flow cell 100 ( Figure 1) of the final fluid flow channel portion (e.g., about 100 μm). Cavity 605 is defined by wall 603 including the highest point of carrier 696. For example, at wall 603 (e.g., FIG. 6B to FIG. 6C ) at the top surface of the carrier 696 and the cover. As will be explained herein, to form this interface, an interface may be applied to the wall 603 (e.g., FIG. 6B to FIG. 6C )'s top surface.

[0108] Figure 6B yes Fig. 6A Horizontal cross-sectional view of the carrier 696. This view shows the electrical contacts 675 in the cavity 605, the sensor structure 142 ( Figure 1 ) via sensor structure 142 ( Figure 1 ) of the electrical contacts (eg, pillar bump 170 and pad 160) and the above-mentioned bottom filler 173 ( Figure 1 ) to electrically couple to electrical contacts 675. In this view, the height difference between sensor structure cavity portion 609, fluid flow channel portion 611, and wall 603 is more obvious. Some examples of electrical contacts 675 are also shown. At the top surface 614 of wall 603, carrier 696 can be connected to cover 190 (e.g., Figure 1 ) junction.

[0109] Figure 6C is a vertical cross-sectional view of the carrier 696. From this vantage point, the vertical height differences between the sensor structure cavity portion 609, the fluid flow channel portion 611, and the wall 603 that bounds the entire cavity 605 are more apparent.

[0110] 7A to 7E Shown is the method for forming Figure 1 Certain aspects of the method of the flow cell 100. Fig. 7A yes Fig. 6A Another cross-sectional view of the carrier 696. Although not visually Fig. 6A (because the horizontal distance of the wall 703 from the sensor structure cavity portion 709 (which can also be understood as the tube core cavity portion) is different throughout the fluid flow channel portion 711), but Fig. 7AA carrier 796 (similar to carrier 696) is depicted, which includes a sensor structure cavity portion 709, a fluid flow channel portion 711 (which may also be understood as a fluid cavity portion), and a wall 703. Carrier 796 includes a substrate and may be formed of materials including, but not limited to, a printed circuit board (PCB) and / or a ceramic circuit board. Electrical contacts 775 on the substrate of carrier 796 are exposed so that they can be electrically coupled to a sensor structure (not shown). Carrier 796 includes internal wires (not shown) to route signals from the bottom (back side) of the sensor structure (not shown) to the back side of carrier 727. Thus, carrier 796 includes features (e.g., thermal vias) that enable heat transfer from the back side of carrier 727 to the sensor structure (e.g., the CMOS of the structure).

[0111] See also Figure 7B , as shown herein, the die (i.e., sensor structure 742) is picked up and placed in the sensor structure cavity portion 709 so that one or more electrical contacts (e.g., TSV 720, column bump 770, raised backside pad) are coupled to electrical contacts 775 on substrate 727 of carrier 796. In this example, the die or sensor structure 742 is singulated. In some examples, a portion of the die or sensor structure is coated with a polymer material. The polymer material can be, for example, a gel-based material such as a polyacrylamide gel coating, including, for example, poly(N-(5-azidoacetamidopentyl)acrylamide-co-acrylamide-co-acrylonitrile) ("PAZAM"). In one example, the die or sensor structure includes at least one nanopore at the surface, and the coating is present at the bottom and / or sidewall portion of the nanopore. After applying the coating, at least a portion of the coating is polished. The die or sensor structure 742 can be coated before or after assembly with the carrier 796. In one example, the die or sensor structure 742 is coated prior to assembly with the carrier 796. When the sensor structure 742 is picked and placed into the sensor structure cavity portion 709, electrical connections are established (e.g., by reflowing the stud bumps 770, establishing contact between the stud bumps 770 and the electrical contacts 775 using an anisotropic conductive film).

[0112] Figure 7CThe formation of the bottom filler 773 layer is shown, which can be accomplished by dispensing a given volume of bottom filler material. As previously discussed, in the example shown herein, the bottom filler 773 provides an interface between the sensor structure 742 and the substrate 797. Low viscosity epoxy resin materials are examples of possible bottom filler materials. Specific bottom filler materials that can be utilized in the example shown include Loctite Eccobond series (Henkel) and / or EP29LPTCHT (MasterBond). In one example, the bottom filler material is a low viscosity epoxy resin material that is available at about -65°F to about +250°F and has a viscosity of about 200cps at about 75°F. The bottom filler can achieve a thickness of about 10μm to about 500μm after bonding, which depends in part on what is packaged under the die and the total stack thickness.

[0113] exist Fig.7D , the fan-out region 780 is formed by depositing a curable material to fill the remainder of the sensor structure cavity portion 709 (e.g., the unfilled space on either side of the sensor structure 742). Since the portion of the carrier 796 defines the sensor structure cavity portion 709, the curable material constituting the fan-out region 780 can be dispensed without any molding structure. The curable material may include, but is not limited to, epoxy resin and / or adhesive. The method of curing the material may include, but is not limited to, one or more of ultraviolet exposure and / or heat exposure. The curable material is dispensed so that the height of the resulting fan-out region 780 is at least equivalent to the active surface 710 of the sensor structure 742. In some specific implementations, the top surface of the fan-out region 780 has substantially the same height as the top surface of the sensor structure 742. In some specific implementations, the top surface of the fan-out region 780 is flush with the top surface of the sensor structure 742. The fan-out region 780 does not extend into the fluid flow channel portion 711. When implemented, the material (e.g., epoxy, adhesive) forming the fan-out region 780 can flatten or form a smooth transition between the active surface 710 of the sensor structure 742 and the surface of the substrate 797, thereby forming a transition area for fluid to flow. The material can also, for example, cover the gap and connect with the wall 703 (the sidewall of the deeper cavity) at a connecting angle.

[0114] Fig. 7EThe flow cell 700 is shown after forming a fluid flow channel 792 in a fluid flow channel portion 711 of a carrier 796. The fluid flow channel 792 is formed over the active surface 710 of the die (sensor structure 742) by attaching a cap 790 to a portion of the carrier 796 adjacent to the fan-out region 780 to form a fluid flow channel between the active surface 710 and the cap 790. For example, an adhesive is applied to the cap 790 and the carrier 796 at an upper surface of each wall 703 of the carrier 790. The adhesive forms an interface 793 between the upper surface of each wall 703 of the carrier 790 and the cap 790.

[0115] Fig. 8A is to use 7A to 7E The method shown is a top view of the flow cell 800 formed. This can also be understood as Fig. 7E 800 in FIG. 8 . As can be seen from this view, the sensor structure 842 can be seen through the translucent cover 890. The sensor structure 842 is positioned in the sensor structure cavity portion 809 (which can also be understood as the tube core cavity portion). Also shown is the wall 803 of the fluid flow channel portion 811 (which can also be understood as the fluid cavity portion) and the interface 893. Fig. 8A As shown, the fluid flow channel portion 811 extends at different points defined by the wall 803, thereby varying the horizontal distance from the sensor structure cavity portion 809 that houses the sensor structure 842. In this example, the shape is a triangle on either side of the sensor structure cavity portion 809. Figure 8B is a horizontal cross-sectional view of the flow cell 800, a portion of which is Fig. 7E are described in the discussion of .

[0116] Figure 8C is a vertical cross-sectional view of the flow cell 800. From this perspective, the fluid holes 867 (providing fluid inlet and / or outlet in the (micro)fluidic flow channel 892) are visible in the cover 890. The shape and orientation of the cavity 805 in the carrier 896 changes the shape of the (micro)fluidic flow channel 892.

[0117] according to Figure 5 Certain aspects of the general workflow 500, FIG. 9A to FIG. 11B Shown in more detail Figure 2 Examples of various aspects of the formation of the flow cell 200.

[0118] See first Fig.9A , and also Figure 2 The vector 296 ( Figure 2), a top view of carrier 996, which includes substrate 997. Cavity 905 in carrier 996 has a single section (i.e., sensor structure cavity portion 909 (which can also be understood as die cavity portion)) that is approximately, and in some cases exactly, the vertical height of sensor structure 942 (the height is the height after sensor structure 942 is picked up and placed in cavity 905 on bottom filler + / - standard tolerance; for example, standard tolerance can be in the range of about + / -1 μm to about + / -10 μm). Cavity 905 (which is entirely sensor structure cavity portion 909) is defined by wall 903 (which is the highest point of carrier 996) FIG. 9B to FIG. 9C ) is defined. In order to form the cover 290 ( Figure 2 ) and the carrier 996, and an interface is formed between the tall structure (spacer) attached to the top surface of the wall 903 and the cover 990.

[0119] Fig. 9B yes Fig.9A Horizontal cross-sectional view of the carrier 996. This view shows the electrical contacts 975 in the cavity 905, the sensor structure 242 ( Figure 2 ) will be transmitted via the sensor structure 242 ( Figure 2 ) of the electrical contacts (eg, pillar bump 170 and pad 160) and the above-mentioned bottom filler 273 ( Figure 2 ) to electrically couple to electrical contacts 975. In this example, a tall structure (spacer) attached to the top surface of wall 903 is electrically coupled to cover 290 ( Figure 2 ) to form a (micro) fluid flow channel 292 ( Figure 2 ).

[0120] FIG. 10A to FIG. 10E Shown is the method for forming Figure 2 Certain aspects of the method of the flow cell 200. Fig. 10A yes Fig. 10A Another cross-sectional view of carrier 1096. Fig. 10A A carrier 1096 (similar to carrier 996) is depicted having only a sensor structure cavity portion 1009 (which may also be understood as a die cavity portion) that includes a cavity 1005 defined by walls 1003. Carrier 1096 includes a substrate and may be formed of materials including, but not limited to, a printed circuit board (PCB) and / or a ceramic circuit board. Electrical contacts 1075 on the substrate of carrier 1096 are exposed so that they can be electrically coupled to a sensor structure (not shown). Carrier 1096 includes internal wires (not shown) to route signals from the bottom (back side) of the sensor structure (not shown) to the back side of carrier 1027. Thus, carrier 1096 includes features (e.g., thermal vias) that enable heat transfer from the back side of carrier 1027 to the sensor structure (e.g., the CMOS of the structure).

[0121] See also Fig. 10B , as shown herein, the die (i.e., sensor structure 1042) is picked up and placed in the sensor structure cavity portion 1009 so that one or more electrical contacts (e.g., TSV 1020, column bump 1070, raised backside pad) are coupled to electrical contacts 1075 on the substrate of the carrier 1096. In this example, the die or sensor structure 1042 is singulated. In some examples, a portion of the die or sensor structure is coated with a polymer material. The polymer material can be, for example, a gel-based material, such as a polyacrylamide gel coating, including, for example, poly(N-(5-azidoacetamidopentyl)acrylamide-co-acrylamide-co-acrylonitrile) ("PAZAM"). In one example, the die or sensor structure includes at least one nanopore at the surface, and the coating is present at the bottom and / or sidewall portion of the nanopore. After applying the coating, at least a portion of the coating is polished. The die or sensor structure 1042 can be coated before or after assembly with the carrier 1096. In one example, the die or sensor structure 1042 is coated prior to assembly with the carrier 1096. When the sensor structure 1042 is picked and placed into the sensor structure cavity portion 1009, electrical connections are established (e.g., by reflowing the stud bumps 1070, establishing contact between the stud bumps 1070 and the electrical contacts 1075 using an anisotropic conductive film).

[0122] Fig. 10C The formation of a bottom filler 1073 layer is shown, which can be accomplished by dispensing a given volume of bottom fill material. A low viscosity epoxy material is an example of a possible bottom fill material. Specific bottom fill materials that can be utilized in the illustrated examples include Loctite Eccobond series (Henkel) and / or EP29LPTCHT (MasterBond). In one example, the bottom fill material is a low viscosity epoxy material that is usable at about -65°F to about +250°F and has a viscosity of about 200 cps at about 75°F. The bottom filler can achieve a thickness of about 10 μm to about 500 μm after bonding, which depends in part on what is packaged under the die and the total stack thickness. As previously discussed, in the examples illustrated herein, the bottom filler 1073 provides an interface between the sensor structure 1042 and the substrate 1097.

[0123] exist Fig. 10D, the fan-out region 1080 is formed by depositing a curable material to fill the remainder of the sensor structure cavity portion 1009 (e.g., the unfilled space on either side of the sensor structure 1042 in the cavity 1005). Since a portion of the carrier 1096 (e.g., the wall 1003) defines the sensor structure cavity portion 1009, the curable material constituting the fan-out region 1080 can be dispensed without any molding structure. The curable material can include, but is not limited to, epoxy and / or adhesive. The method of curing the material can include, but is not limited to, one or more of ultraviolet exposure and / or thermal exposure. The curable material is dispensed so that the resulting fan-out region 1080 is approximately as tall as the wall 1003 of the carrier 1096. Thus, an adjoining surface is formed that includes the top surface of the wall 1014 of the carrier 1096, the fan-out region 1080, and the active surface 1010 of the sensor structure 1042 (e.g., the die). When implemented, the material (e.g., epoxy, adhesive) forming the fan-out region 1080 can flatten or form a smooth transition between the active surface 1010 of the sensor structure 1042 and the surface of the substrate 1097, thereby forming a transition area for fluid to flow. The material can also, for example, cover the gap and connect with the wall 1003 (the sidewall of the deeper cavity) at a connecting angle.

[0124] Fig. 10E The flow cell 1000 is shown after forming the fluid flow channel 1092. A high structure 1077 (e.g., a spacer) is attached to a portion of the top surface of the wall 1014 of the carrier 1096. The spacer can be made of various materials, including but not limited to adhesives (e.g., double-sided adhesives), epoxies, epoxies with solid fillers, etc. For example, the spacer can be a thin layer of about 10-50-100-500 μm thick glued to both sides.

[0125] The fluid flow channel 1092 is formed over the active surface 1010 of the die (sensor structure 1042) by attaching a cap 1090 to the top surface of the tall structure 1077 to form a fluid flow channel 1011 between the active surface 1010 and the cap 1090. For example, an adhesive is applied to the cap 1090 and the top surface of the tall structure 1077. The adhesive forms an interface between the top surface of the tall structure 1077 and the cap 1090.

[0126] Fig.11A is to use FIG. 10A to FIG. 10E The method shown is a top view of the flow cell 1100 formed. This can also be understood as Fig. 10E1000 in a top view of the flow cell 1000. From this view, it can be seen that the sensor structure 1142 can be seen through the translucent cover 1190. The sensor structure 1142 is positioned in the sensor structure cavity portion 1109 (which can also be understood as the tube core cavity portion), and the cavity 1105 is designed into the carrier 1196 before the pick and place process. Since there is a section in this cavity 1105, the sensor structure cavity portion 1109 is the cavity 1105. The fluid flow channel 1192 is defined by the high structure 1177, the active surface 1110 and the cover 1190. Since a portion of the top surface of the wall 1114 is attached to the high structure 1177 (spacer), Fig.11A The (micro) fluid flow channel 1192 is similar in shape to Fig. 8A (micro) fluid flow channel 892. This shape enables these two examples to share similar utility. Some examples of shapes that achieve good jetting (for the purposes described herein) and fluid exchange include, but are not limited to, diamond shapes and rugby shapes. Fig. 11B is a horizontal cross-sectional view of the flow cell 1100, a portion of which is shown in FIG. Fig. 10E are described in the discussion of .

[0127] Fig. 11C is a vertical cross-sectional view of the flow cell 1100. From this perspective, the fluid holes 1167 (providing fluid inlet and / or outlet in the (micro)fluidic flow channel 1192) are visible in the cover 1190. The shape and orientation of the cavity 1105 in the carrier 1196 changes the shape of the (micro)fluidic flow channel 1192.

[0128] FIG. 12A to FIG. 14C Shown in more detail Figure 3 Examples of various aspects of the formation of the flow cell 300. These carriers formed using the methods discussed below do not utilize TSVs to provide electrical and / or thermal conductivity. Therefore, there are certain differences in the carriers to accommodate this difference in sensor structure.

[0129] Fig. 12A Yes also Figure 3 A top view of a carrier 396, 1296 is depicted in FIG. 1 , the carrier including a substrate 397. FIG. 6A to FIG. 6C In the same way as in the cavity in the formation of the flow cell 300 ( Figure 3 ), the cavity 1205 in the carrier 1296 has different sections of different depths (heights) for different purposes. However, because these electrical connections are different, different parts of the cavity 1205 are used for different purposes. FIG. 12A to FIG. 12C, which provide a clearer illustration of certain aspects in the form of various views. One section of the cavity 1205 (i.e., the sensor structure cavity portion 1209 (which can also be understood as the tube core cavity portion)) is approximately, and in some cases exactly, the vertical height of the active surface of the sensor structure (this height is the height after the sensor structure is picked up and placed in the cavity 1205 + / - standard tolerance; the standard tolerance depends in part on the material and process application, but in this example, the standard tolerance can be about + / - 1 to 10 μm). The second section (i.e., the fluid flow channel portion 1211 (which can also be understood as the fluid cavity portion)) has a depth (e.g., about 100 μm) that starts at the top of the sensor structure cavity portion 1209 and defines the height of the final fluid flow channel portion of the flow cell 1200. The third section (i.e., the wire bonding package portion 1224) is located only on two sides of the carrier 1296, thereby Fig. 12B and Fig. 12A Visible in Fig. 12C 1205. The third section has a depth that starts at the top of the sensor structure cavity portion 1209. The cavity 1205 is bounded by the wall 1203, which is the highest point of the carrier 1296. In the illustrated example, at the top surface of the wall 1203, the carrier 1296 interfaces with the cap. However, the cap also interfaces with a portion of the packaged electrical connection. As will be explained herein, to form this interface, an interface can be applied to the top surface 1214 of the wall 1203 and a portion of the package of the electrical connection.

[0130] Fig. 12B yes Fig. 12A 1296 of the carrier 1296. This view shows the electrical contacts, namely the top side substrate bonding pads 1241 located in the wire bond package portion 1224 of the cavity 1205. The sensor structure 342 ( Figure 3 ) through the welding wire 331 ( Figure 3 ) from sensor structure 342 ( Figure 3 ) of the electrical contacts (e.g., bonding pads 337 on the die ( Figure 3 )) are electrically coupled to these top side substrate bonding pads 1241. In this view, the height difference between the sensor structure cavity portion 1209, the wire bonding package portion 1224, and the wall 1203 is more obvious. To potentially enhance thermal performance, thermal vias can be integrated into the carrier 1296.

[0131] Fig. 12C is a vertical cross-sectional view of the carrier 1296. From this vantage point, the vertical height differences between the sensor structure cavity portion 1209, the fluid flow channel portion 1211, and the wall 1203 that defines the entire cavity 1205 are more apparent.

[0132] FIG. 13A to FIG. 13E Shown is the method for forming Figure 3Certain aspects of the method of the flow cell 300. Fig.13A yes Fig. 12A Another cross-sectional view of the carrier 1296. Although not visually Fig. 12A (because the horizontal distance of the wall 1203 from the sensor structure cavity portion 1209 is different throughout the wire bonding package portion 1224), but Fig.13A A carrier 1396 (similar to carrier 1296) is depicted, which includes a sensor structure cavity portion 1309 (which may also be understood as a tube core cavity portion), a wire bonding package portion 1324, and a wall 1303. Carrier 1396 includes a substrate and may be formed of materials including, but not limited to, a printed circuit board (PCB) and / or a ceramic circuit board. Electrical contacts on the substrate include top-side substrate bonding pads 1341, which are located at the lowest vertical height (base surface) of the wire bonding package portion 1324 on the carrier 1396 so that they can be electrically coupled to the sensor structure (not shown). Connections between the layers of substrate 1397 (e.g., additional metal layers of the substrate / PCB, and through-hole connections between the layers are not shown) are not shown, and these connections include internal wires for routing signals from the bottom of the bonding pads 1341 to the back side of the carrier 1327.

[0133] See also Fig. 13B , as shown herein, the die (i.e., sensor structure 1342) is picked up and placed in the sensor structure cavity portion 1309. In this example, the die or sensor structure 1342 is singulated. In some examples, a portion of the die or sensor structure is coated with a polymer material. The polymer material can be, for example, a gel-based material, such as a polyacrylamide gel coating, including, for example, poly(N-(5-azidoacetamidopentyl)acrylamide-co-acrylamide-co-acrylonitrile) ("PAZAM"). In one example, the die or sensor structure includes at least one nanopore at the surface, and the coating is present at the bottom and / or sidewall portion of the nanopore. After applying the coating, at least a portion of the coating is polished. The die or sensor structure 1342 may be coated before or after assembly with the carrier 1396. In one example, the die or sensor structure 1342 is coated before assembly with the carrier 1396. Fig. 13B Also shown is the formation of an underfill 1373 layer, which may be accomplished by dispensing a given volume of underfill material, as discussed in Figures 7 and 11. As previously discussed, underfill 1373 provides an interface between sensor structure 1342 and substrate 1397 in the examples shown herein.

[0134] exist Fig. 13C1309 (e.g., the unfilled space on either side of the sensor structure 1342). Since the portion of the carrier 1396 defines the sensor structure cavity portion 1309, the curable material constituting the fan-out region 1380 can be dispensed without any molding structure. The curable material may include, but is not limited to, epoxy resin and / or adhesive. The method of curing the material may include, but is not limited to, one or more of ultraviolet exposure and / or thermal exposure. The curable material is dispensed so that the height of the resulting fan-out region 1380 is at least comparable to the active surface 1310 of the sensor structure 1342. The fan-out region 1380 does not extend into the wire bonding package portion 1324 of the cavity 1309.

[0135] Fig.13D The top side substrate bonding pad 1341 is shown wire bonded to a pad on a carrier 1337 in a wire bond package portion 1324 of a cavity 1309. The wirebond may be composed of one or more metals such as aluminum, copper, silver, gold, or any combination thereof. The metal in the wirebond may be in elemental form, alloy form, or composite form. For example, the wirebond may include, for example, forming a eutectic metal bond.

[0136] Fig.13E The wire bond connections are shown encapsulated (the package forming connection 1328). One or more pins may be used to ensure that the material used for encapsulation 1328 (e.g., a curable material, which may be the same material used to form fan-out region 1380) does not flow onto active surface 1310 of sensor structure 1342. During encapsulation of the connections (including wirebonds 1331, bond pads 1337 (on the die), and top-side substrate bond pads 1341 (on substrate 1397), the wire bond encapsulation portion 1324 of the cavity is filled with curable material. The top surface of encapsulation 1328 (e.g., adhesive, epoxy) may not be flat initially and may flatten when a glass cover is placed, such as Fig.13F As shown. Encapsulation 1328 partially defines the fluid flow channel, so the shape of the sidewalls of encapsulation 1328 can contribute to the effectiveness of the flow cell. For example, the walls of encapsulation 1328 (e.g., adhesive / dam) can be straight and can also be angled or curved.

[0137] Fig.13FThe flow cell 1300 is shown after forming a fluid flow channel 1392 in a fluid flow channel portion 1311 (which may also be understood as a fluid cavity portion) of the cavity 1309, which is not filled with material when these connections are packaged because the wire bonding package portion 1324 is located only on one side. The fluid flow channel 1392 is formed above the active surface 1310 of the die (sensor structure 1342) by attaching a cap 1390 to a portion of the carrier 1396 adjacent to the fan-out area 1380 and / or a top surface of the package 1328 to form a fluid flow channel between the active surface 1310 and the cap 1390. For example, at the upper surface of each wall 1303 of the carrier 1390, an adhesive is applied to the cap 1390 and the carrier 1396. The adhesive forms an interface between the upper surface of each wall 1303 of the carrier 1390 or the top surface of the package 1328 and the cap 1390.

[0138] Fig.14A is to use FIG. 13A to FIG. 13F The method shown is a top view of the flow cell 1400 formed. This can also be understood as Fig.13F 14. A top view of the flow cell 1300 in FIG. 14. As can be seen from this view, the sensor structure 1442 can be seen through the translucent cover 1490. The sensor structure 1442 is positioned in the sensor structure cavity portion 1409 (which can also be understood as the tube core cavity portion) of the cavity 1405. The fluid flow channel portion 1411 (which can also be understood as the fluid cavity portion) of the cavity 1405 is also shown. Fig.14A , Fig. 14B and Fig. 14C As shown in different parts of FIG. 14 , the fluid flow channel portion 1411 extends at different points defined by the package 1428 on two sides (encapsulating the bonding pads 1437 on the die) and the wall 1403 on the other side, thereby defining a (micro) fluid flow channel 1492. The wall 1403 has different horizontal distances from the sensor structure cavity portion 1409 that accommodates the sensor structure 1442. In this example, the shape is a triangle on either side of the sensor structure cavity portion 1409. Fig. 14B is a horizontal cross-sectional view of the flow cell 1400, a portion of which is shown in FIG. Fig.13F are described in the discussion of .

[0139] Fig. 14C 14 is a vertical cross-sectional view of the flow cell 1400. From this perspective, the fluid holes 1467 (providing fluid inlet and / or outlet in the (micro)fluid flow channel 1492) are visible in the cover 1490. It will be appreciated that the (micro)fluid flow channel 1492 can be shaped using the shape and orientation of the cavity 1405 in the carrier 1496. By contrast Fig. 14C and Fig.13FAs can be clearly seen from the view of FIG. 14 , although the (micro) fluid flow channel 1492 is defined on two sides by parts of the package 1428 , it is also defined on the other two sides by walls 1403 that define the fluid flow channel part 1411 .

[0140] FIG. 15A to FIG. 17C Shown in more detail Figure 4 Examples of various aspects of the formation of the flow cell 400. These carriers formed using the methods discussed below do not utilize TSVs to provide electrical and / or thermal conductivity. Therefore, certain differences exist in the carriers to accommodate this difference in electrical connection structure.

[0141] Fig.15A Yes also Figure 4 A top view of a carrier 496, 1596 is depicted in FIG. 1 , which includes a substrate 497. Fig. 15B is a horizontal cross section of the carrier and Fig. 15C is a vertical cross-section of the carrier. When taking cavity 1505 into account, the carrier 1596 including the substrate 1597 can be understood as having four (4) levels. The substrate 1597 can be composed of a PCB and / or a ceramic circuit board. One section of the cavity 1505 (i.e., the sensor structure cavity portion 1509 (which can also be understood as the tube core cavity portion)) is approximately and in some cases exactly the vertical height of the active surface of the sensor structure (this height is the height after the sensor structure is picked up and placed on the bottom fill layer in the cavity 1505 + / - standard tolerance; a non-limiting example of a standard tolerance can be approximately + / - 1 to 10 μm). The second section (i.e., the fluid flow channel portion 1511 (which can also be understood as the fluid cavity portion)) has a flow pool 400 (starting at the top of the sensor structure cavity portion 1509 and defining it). Figure 4 ) of the final fluid flow channel portion (e.g., about 100 μm). Cavity 1505 is defined by wall 1503, which is the highest point of carrier 1596. For example, at the top surface of wall 1503, carrier 1596 interfaces with the cap. However, the cap also interfaces with a portion of the packaged electrical connection. As will be explained herein, to form this interface, an interface can be applied to the top surface of wall 1503 and a portion of the package of the electrical connection.

[0142] Fig. 15B yes Fig.15A Horizontal cross-sectional view of the carrier 1596 of FIG. 15. This view shows the electrical contacts, namely the top side substrate bonding pads 1541 located in the sensor structure cavity portion 1509. The fluid flow channel portion 1511 is not visible from this vantage point. The sensor structure 442 ( Figure 4 ) through the welding wire 431 ( Figure 4 ) from sensor structure 442 ( Figure 4 ) of an electrical contact (e.g., bonding pad 437 on the die ( Figure 4 )) is electrically coupled to these top side substrate bonding pads 1541. In this view, the height difference between the sensor structure cavity portion 1509 and the wall 1503 is obvious. To potentially enhance thermal performance, thermal vias can be integrated into the carrier 1596.

[0143] Fig. 15C is a vertical cross-sectional view of the carrier 1596. From this vantage point, the vertical height differences between the sensor structure cavity portion 1509, the fluid flow channel portion 1511, and the wall 1503 that defines the entire cavity 1505 are more apparent.

[0144] FIG. 16A to FIG. 16E Shown is the method for forming Figure 4 Certain aspects of the method of the flow cell 400. Fig.16A yes Fig.15A Another cross-sectional view of the carrier 1596. Although not visually Fig.15A (because the horizontal distance of the wall 1503 from the sensor structure cavity portion 1509 is different throughout the wire bonding package portion 1524), but Fig.16A A carrier 1696 (similar to carrier 1596) is depicted, which includes a sensor structure cavity portion 1609 (which may also be understood as a tube core cavity portion), a fluid flow channel portion 1611 (which may also be understood as a fluid cavity portion), and a wall 1603. Carrier 1696 includes a substrate and may be formed of materials including, but not limited to, a printed circuit board (PCB) and / or a ceramic circuit board. The electrical contacts on the substrate include top-side substrate bonding pads 1641, which are located at the lowest vertical height (base surface) of the sensor structure cavity portion 1609 on the carrier 1696 so that they can be electrically coupled to the sensor structure (not shown), and the sensor structure can be centered in the sensor structure cavity portion 1609 relative to these top-side substrate bonding pads 1641. Connections between the layers of substrate 1697 (e.g., additional metal layers of the substrate / PCB, and through-hole connections between the layers are not shown) are not shown, including internal wires for routing signals from the bottom of bonding pads 1641 to the back side of carrier 1627.

[0145] See also Fig. 16B, as shown herein, the die (i.e., sensor structure 1642) is picked up and placed in the sensor structure cavity portion 1609. In this example, the die or sensor structure 1642 is singulated. In some examples, a portion of the die or sensor structure is coated with a polymer material. The polymer material can be, for example, a gel-based material, such as a polyacrylamide gel coating, including, for example, poly(N-(5-azidoacetamidopentyl)acrylamide-co-acrylamide-co-acrylonitrile) ("PAZAM"). In one example, the die or sensor structure includes at least one nanopore at the surface, and the coating is present at the bottom and / or sidewall portion of the nanopore. After applying the coating, at least a portion of the coating is polished. The die or sensor structure 1642 may be coated before or after assembly with the carrier 1696. In one example, the die or sensor structure 1642 is coated before assembly with the carrier 1696. Fig. 16B Also shown is the formation of an underfill 1673 layer, which may be accomplished by dispensing a given volume of underfill material, as discussed with reference to Figures 7 and 11. As previously discussed, in the examples shown herein, underfill 1673 provides an interface between sensor structure 1642 and substrate 1697.

[0146] Fig. 16C It is shown that in the sensor structure cavity portion 1609, the top side substrate bonding pad 1641 is wire bonded to the pad on the carrier 1637. The bonding wire can be composed of one or more metals such as aluminum, copper, silver, gold, or any combination thereof. The metal in the bonding wire can be in elemental form, alloy form, or composite form. For example, the wire bonding can include, for example, forming a eutectic metal bond.

[0147] exist Fig.16D , the fan-out region 1680 is formed by depositing a curable material to fill the remainder of the sensor structure cavity portion 1609 (e.g., the unfilled space on either side of the sensor structure 1642) and these connected packaging portions. Since the portion of the carrier 1696 defines the sensor structure cavity portion 1609, the curable material constituting the fan-out region 1680 can be dispensed without any molding structure. The curable material may include, but is not limited to, an epoxy resin and / or an adhesive. The method of curing the material may include, but is not limited to, one or more of ultraviolet exposure and / or thermal exposure. The curable material is dispensed so that the height of the resulting fan-out region 1680 is at least equivalent to the active surface 1610 of the sensor structure 1642. The fan-out region 1680 does not extend into the fluid flow channel portion 1611 of the cavity 1609.

[0148] Fig.16EThe remainder of the connection encapsulating the wire bond is shown (the encapsulation forming connection 1628). One or more pins may be used to ensure that the material used for encapsulation 1628 (e.g., a curable material, which may be the same material used to form fan-out region 1680) does not flow onto active surface 1610 of sensor structure 1642. The top surface of encapsulation 1628 (e.g., adhesive, epoxy) may not be flat initially and may flatten when the glass cover is placed, such as Fig.16F As shown. Encapsulation 1628 partially defines the fluid flow channel, so the shape of the sidewalls of encapsulation 1628 can contribute to the effectiveness of the flow cell. For example, the walls of encapsulation 1628 (e.g., adhesive / dam) can be straight and can also be angled or curved.

[0149] Fig.16F Flow cell 1600 is shown after forming fluid flow channel 1692 in fluid flow channel portion 1611 of cavity 1609, which is not filled with material when these connections are packaged. Fluid flow channel 1692 is formed over active surface 1610 of die (sensor structure 1642) by attaching cap 1690 to a portion of carrier 1696 adjacent to fan-out region 1680 and / or a top surface of package 1628 to form a fluid flow channel between active surface 1610 and cap 1690. For example, at an upper surface of each wall 1603 of carrier 1690, an adhesive is applied to cap 1690 and carrier 1696. The adhesive forms an interface between an upper surface of each wall 1603 of carrier 1690 or a top surface of package 1628 and cap 1690.

[0150] Fig.17A is to use FIG. 16A to FIG. 16F The method shown is a top view of the flow cell 1700 formed. This can also be understood as Fig.16F 17 is a top view of the flow cell 1600 in FIG. 17. As can be seen from this view, the sensor structure 1742 can be seen through the translucent cover 1790. The sensor structure 1742 is positioned in the sensor structure cavity portion 1709 (which can also be understood as the tube core cavity portion). The fluid flow channel portion 1711 (which can also be understood as the fluid cavity portion) is also shown. Fig.17A As shown, the fluid flow channel portion 1711 extends at different points defined by the package 1728, thereby varying the horizontal distance from the sensor structure cavity portion 1709 that houses the sensor structure 1742. In this example, the shape is a triangle on either side of the sensor structure cavity portion 1709. Fig. 17B is a horizontal cross-sectional view of the flow cell 1700, a portion of which is shown in FIG. Fig.16E are described in the discussion of .

[0151] Fig. 17C 17 is a vertical cross-sectional view of the flow cell 1700. From this perspective, the fluid holes 1767 (providing fluid inlet and / or outlet in the (micro)fluid flow channel 1792) are visible in the cover 1790. It should be understood that the (micro)fluid flow channel 1792 can change shape based on the shape and orientation of the cavity 1705 in the carrier 1796. By contrast Fig. 17B and Fig. 17C It can be clearly seen from the view of that, although the (micro) fluid flow channel 1792 is defined on two sides by parts of the package 1728, it is also defined on the other two sides by the wall 1703 that defines the fluid flow channel part 1711.

[0152] Many of the examples shown so far show flow cells that may include a single die. However, some flow cells may include more than one die, each die being located in a separate cavity and / or portion of a cavity in a carrier including a substrate. 18A to 18C Some aspects of an example having multiple sensor structures are shown. Fig.18A is a top view of a flow cell 1800 formed using a carrier 1896 having more than one cavity 1805 . Fig.18B is a horizontal cross-sectional view of the flow cell 1800, and Fig.18C 1800 is a vertical cross-sectional view of a flow cell 1800. The example shown has two cavities 1805, but additional examples may or may not have more than two cavities 1805. In examples where there are multiple cavities in the substrate, the cavities are along the same plane, such as 18A to 18C As shown. Fig.18A From the top view, both cavities 1805 in this particular example are along the same plane. Fig.18A Top perspective view and Fig.18C As can be seen in the vertical cross-sectional view of , two sensor structures 1842 are placed (e.g., using a pick and place process) into a cavity 1805 in a carrier 1896. The carrier 1896 includes a sensor structure cavity portion 1809 (which can also be understood as a die cavity portion) that accommodates the two sensor structures 1842, and a fan-out region 1880 formed in each cavity portion 1809 that accommodates the sensor structure 1842. The carrier 1896 also includes a fluid flow channel portion 1811 (which can also be understood as a fluid cavity portion, in which a (micro) fluid flow channel 1892 is formed). Fig.18A The examples shown in FIG. 1 to C include TSVs 1820 that participate in electrical properties, but examples utilizing bonding pads can also be integrated into a carrier 1896 having this type of cavity. 18A to 18C The middle cover 1890 is attached at the interface with the top surface of the wall 1814 of the cavity, but the interface with the cover can also be formed in the spacer. The cover 1890 includes a fluid hole 1867.

[0153] As previously mentioned, the flow cell described and illustrated herein enables heat transfer from a silicon wafer (e.g., CMOS). This aspect may or may not be enhanced by adding thermal vias 1964 (e.g., made of copper), particularly for thermal management, to directly access the die (e.g., CMOS) for heating with a heating element 1962, such as Fig.19 As described. FIG. 20A to FIG. 20B As depicted in the absence of thermal vias 1964 ( Fig.19 ) in which the structural changes enable contact with the backside surface 2063 of the silicon wafer die 2030 in the sensor structure 2042 of the flow cell 2000. Fig. 20A In the embodiment, a through cut 2043 is implemented to couple the heating element 2062 to the backside surface 2063 of the silicon wafer die 2030 in the sensor structure 2042 of the flow cell 2000. Fig. 20B In the embodiment, the carrier 2096 includes a thermal via cavity 2047 , and thus the heating element 2062 may be coupled to the backside surface 2063 upon being inserted into the thermal via cavity 2047 .

[0154] In some examples of the methods described herein, the method includes placing a die in a portion of a cavity in a substrate, wherein one or more electrical contacts on a surface of the die are accessible. In some examples, the substrate includes exposed electrical contacts accessible to the electrical contacts on the surface of the die. The placement may include defining a first space in the cavity adjacent to a first edge of the upper surface of the die and a second space in the cavity adjacent to a second edge of the upper surface of the die. The method may also include forming a bottom fill layer in the cavity between the lower surface of the die and the substrate. The method may include forming a fluid fan-out region by depositing a curable material in the first space and the second space to form a fluid fan-out region, the surfaces of which are adjacent to the upper surface of the die. The method may include forming a fluid flow channel above the active surface of the die, including: attaching a cap to a portion of the substrate adjacent to the fluid fan-out region to form a fluid flow channel between the active surface and the cap.

[0155] In some examples of the method, the placing further includes coupling exposed electrical contacts to the electrical contacts.

[0156] In some examples, the method also includes coupling the exposed electrical contacts to electrical contacts on the surface of the die.

[0157] In some examples of the method, the exposed electrical contacts and the electrical contacts on the surface of the die constitute bonding pads, including the bonding pads of the exposed electrical contacts each oriented in one of the first space or the second space, and the coupling includes wire bonding each of the exposed electrical contacts to one of the electrical contacts on the surface of the die to form a wire bonding connection.

[0158] In some examples, the method further includes encapsulating the wire bond connections by depositing a curable material over the fluid fan-out region prior to forming the fluid flow channel.

[0159] In some examples, forming the fluid flow channel over the active surface of the die further includes orienting the cap in physical contact with a top surface of each of the packaged wirebond connections, wherein the orientation flattens each top surface.

[0160] In some examples of the method, the die also includes a silicon wafer, a passivation stack, and one or more through-silicon vias extending through a portion of the silicon wafer and the passivation stack, wherein the passivation stack is disposed below a lower surface of the portion of the silicon wafer, wherein a portion of each of the one or more through-silicon vias is exposed through one of the one or more openings in the passivation stack, and wherein each exposed portion is coupled to an electrical contact.

[0161] In some examples, placing also includes coupling the exposed electrical contacts to the electrical contacts.

[0162] In some examples, the method also includes coupling the exposed electrical contacts to electrical contacts on the surface of the die.

[0163] In some examples, the coupling includes utilizing a method selected from the group consisting of: reflowing the electrical contacts, wherein the electrical contacts of the die include stud bumps, and utilizing an anisotropic conductive film to couple the electrical contacts to the exposed electrical contacts.

[0164] In some examples of the method, the curable material is selected from the group consisting of epoxies and adhesives.

[0165] In some examples of the method, forming the fluid fan-out region further includes curing the curable material.

[0166] In some examples, the curing includes utilizing a method selected from the group consisting of: exposing the curable material to ultraviolet radiation and exposing the curable material to thermal energy.

[0167] In some examples of the method, the die includes a sensor.

[0168] In some examples of the method, the sensor includes a complementary metal oxide semiconductor (CMOS) detection device.

[0169] In some examples of the method, the cavity includes: a die cavity portion, a fluid cavity portion, and a top-level portion, wherein the die cavity portion and the bottom fill layer together have a height substantially equal to the die, wherein the fluid cavity portion includes a space having a height of a fluid flow channel, and wherein the top-level portion has a height of a portion of the substrate adjacent to the fluid fan-out region.

[0170] In some examples, placing the die in the portion of the cavity in the substrate includes placing the die in a die cavity portion of the substrate.

[0171] In some examples of the method, the portion of the substrate adjacent to the fluid fan-out region includes a portion of a circuit board, and the top-level portion includes an interface between the circuit board and the cover.

[0172] In some examples of the method, the cover includes an inlet for the fluid and an outlet for the fluid.

[0173] In some examples, attaching the cover includes applying an adhesive between the circuit board and the cover.

[0174] In some examples of the method, die are singulated from a silicon wafer.

[0175] In some examples of the method, the surface of the die is selected from: an upper surface of the die, a portion of the upper surface of the die including the active surface, and a lower surface parallel to the upper surface.

[0176] In some examples of devices described herein, the device includes: a die, wherein one or more electrical contacts on a surface of the die are accessible. The device may also include a substrate, the substrate including a cavity, wherein the die is oriented in a portion of the cavity in the substrate, wherein the substrate includes exposed electrical contacts that are electrically coupled to electrical contacts on the surface of the die, wherein the orientation defines a first space in the cavity adjacent to a first edge of the upper surface of the die and a second space in the cavity adjacent to a second edge of the upper surface of the die. The device may also include fluid fan-out regions, the fluid fan-out regions including a first solidified material deposited in the first space and the second space, the surfaces of the fluid fan-out regions being adjacent to the upper surface of the die.

[0177] In some examples of the device, the device may also include a fluid flow channel above the active surface of the tube core, the fluid flow channel being defined by the surface of the fluid fan-out area and the upper surface of the tube core and a cover attached to a portion of the substrate adjacent to the fluid fan-out area.

[0178] In some examples of the apparatus, the apparatus further includes an underfill layer in the cavity between the lower surface of the die and the substrate.

[0179] In some examples of the apparatus, the dies are singulated from a silicon wafer.

[0180] In some examples of the apparatus, the exposed electrical contacts constitute substrate bond pads and the electrical contacts on the surface of the die constitute die bond pads, and wherein each die bond pad is coupled to at least one substrate bond pad with a wire to form a wire bond connection.

[0181] In some examples of the apparatus, the wire bond connections are encapsulated in the second cured material.

[0182] In some examples of the apparatus, the cap is oriented to physically contact a top surface of each of the packaged wire bonded connections.

[0183] In some examples, the die also includes a silicon wafer, a passivation stack, and one or more through-silicon vias extending through a portion of the silicon wafer and the passivation stack, wherein the passivation stack is disposed below a lower surface of the portion of the silicon wafer, wherein a portion of each of the one or more through-silicon vias is exposed through one of the one or more openings in the passivation stack, and wherein each exposed portion is coupled to an electrical contact.

[0184] In some examples, each of the curable material and the second curable material is selected from: an epoxy resin and an adhesive.

[0185] In some examples, the die includes a sensor.

[0186] In some examples, the sensor includes a complementary metal oxide semiconductor (CMOS) detection device.

[0187] In some examples of the device, the device also includes a bottom fill layer in the cavity between the lower surface of the tube core and the substrate, and the cavity includes: a tube core cavity portion, a fluid cavity portion, and a top portion, wherein the tube core cavity portion and the bottom fill layer have a height substantially equal to the tube core, wherein the fluid cavity portion includes a space having a height of the fluid flow channel, and wherein the top portion has a height of a portion of the substrate adjacent to the fluid fan-out area.

[0188] In some examples, the portion of the cavity in the substrate in which the die is oriented comprises the die cavity portion.

[0189] In some examples, the portion of the substrate adjacent to the fluid fan-out region includes a portion of a circuit board, and the top-level portion includes an interface between the circuit board and the cover.

[0190] In some examples, the cover includes an inlet for the fluid and an outlet for the fluid.

[0191] In some examples, the fluid flow channel is approximately 100 μm from the active surface to the cover.

[0192] In some examples, the circuit board is selected from: a printed circuit board and a ceramic circuit board.

[0193] In some examples, the surface is selected from: an upper surface of the die, a portion of the upper surface of the die including the active surface, and a lower surface parallel to the upper surface.

[0194] In some examples of the methods described herein, the method includes picking up and placing a die including a sensor and one or more electrical contacts accessible on a surface of the die on a cavity surface at a base of a cavity of a carrier, wherein the carrier includes a substrate and a cavity, wherein the substrate includes exposed electrical contacts, and wherein the placement defines a first space in the cavity adjacent to a first edge of the surface of the die and a second space in the cavity adjacent to a second edge of the surface of the die. The method may also include connecting each of the one or more electrical contacts of the die to at least one of the exposed electrical contacts of the substrate. The method may include forming a fluid fan-out region by depositing a curable material in the first space and the second space to form a fluid fan-out region. The method may include attaching a cap to a portion of the substrate adjacent to the fluid fan-out region to form a fluid flow channel between the active surface of the sensor and the cap.

[0195] In some examples of the method, the cavity surface includes an underfill layer.

[0196] In some examples of devices described herein, the device includes a die and a substrate, the substrate including a cavity. In some examples, the die is oriented in a portion of the cavity in the substrate, wherein the orientation defines a first space in the cavity adjacent to a first edge of an upper surface of the die and a second space in the cavity adjacent to a second edge of the upper surface of the die. The device may also include fluid fan-out regions, which include a first solidified material deposited in the first space and the second space, and the surfaces of the fluid fan-out regions are adjacent to the upper surface of the die. The device may also include a fluid flow channel above the active surface of the die, the fluid flow channel being defined by the surface of the fluid fan-out region and the upper surface of the die and a cap attached to a portion of the substrate adjacent to the fluid fan-out region.

[0197] The flow chart and block diagram in the accompanying drawings show the possible specific implementation architecture, function and operation of the system, method and computer program product of various examples specifically implemented according to the present invention.In this regard, each box in the flow chart or block diagram can represent a module, fragment or part of an instruction, including one or more executable instructions for implementing a specified logical function.In some alternative specific implementations, the function noted in the box may not occur in the order noted in the figure.For example, the two boxes shown in succession can actually be executed substantially at the same time, or these boxes can sometimes be executed in the opposite order, depending on the functions involved.It should also be noted that each box in the block diagram and / or the flow chart diagram and the combination of the boxes in the block diagram and / or the flow chart diagram can be implemented by a system based on dedicated hardware that performs a specified function or action or performs a combination of dedicated hardware and computer instructions.

[0198] The terms used herein are for the purpose of describing specific examples only and are 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 should also be understood that when used in this specification, the terms "include" and / or "comprise" specify the presence of the features, integers, steps, processes, operations, elements, and / or parts, but do not exclude the presence or addition of one or more other features, integers, steps, processes, operations, elements, parts, and / or groups thereof.

[0199] The corresponding structures, materials, acts, and equivalents of all means or steps plus functional elements in the following claims, if any, are intended to include any structure, material, or act for performing the function in combination with other claimed elements 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 the disclosed forms. Many modifications and variations will be apparent to those of ordinary skill in the art. The examples are selected and described in order to best explain the various aspects and practical applications, and to enable others of ordinary skill in the art to understand the various examples with various modifications suitable for the particular use contemplated.

[0200] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (assuming such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein to achieve at least the benefits as described herein. Specifically, all combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein. It should also be understood that terms explicitly adopted herein that may also appear in any disclosure incorporated by reference should be given the meaning most consistent with the specific concepts disclosed herein.

[0201] 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 language of the claims.

[0202] It should be understood that the above description is intended to be illustrative and not restrictive. For example, the above examples (and / or their various aspects) can be used in combination with each other. In addition, without departing from the scope of various examples, many modifications can be made to adapt specific situations or materials to the teachings of various examples. Although the size and type of materials described herein are intended to define the parameters of various examples, they are by no means restrictive and are provided only by way of example. When viewing the above description, many other examples will be apparent to those skilled in the art. Therefore, the scope of various examples should be determined with reference to the full scope of the appended claims and the equivalents granted by these claims. In the appended claims, the terms "including" and "wherein" are used as the plain English equivalents of the corresponding terms "including" and "wherein". In addition, in the following claims, the terms "first", "second" and "third" etc. are used only as labels and are not intended to impose numerical requirements on their objects. The form of the term "based on" herein covers the relationship in which the element is partially based on and the relationship in which the element is completely based on. The form of the term "defined" covers the relationship in which the element is partially defined and the relationship in which the element is completely defined. Furthermore, the following claim limitations are not written in a 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 functional recitation without additional structure. It is to be understood that not all such objects or advantages described above may necessarily be achieved according to any particular example. Thus, for example, one skilled in the art will recognize that the systems and techniques described herein may be implemented or performed in a manner that achieves or optimizes one advantage or group of advantages taught herein without necessarily achieving other objects or advantages that may be taught or suggested herein.

[0203] Although only a limited number of examples are described in detail, it should be readily understood that the subject matter is not limited to such disclosed examples. On the contrary, the subject matter may be modified to combine any number of variations, changes, substitutions or equivalent arrangements that have not been described before but are comparable to the essence and scope of the subject matter. In addition, although various examples of the subject matter have been described, it should be understood that the various aspects of the present disclosure may include only some of the examples. In addition, although some examples are described as having a certain number of elements, it should be understood that the subject matter can be practiced with less than or greater than a certain number of elements. Therefore, the subject matter should not be considered to be limited by the foregoing description, but only by the scope of the appended claims.

Claims

1. A method for forming a flow cell, the method comprising: placing a die in a portion of a cavity in a substrate, wherein one or more electrical contacts on a surface of the die are accessible, wherein the substrate includes exposed electrical contacts accessible to the electrical contacts on the surface of the die, wherein the placement defines a first space in the cavity adjacent a first edge of an upper surface of the die and a second space in the cavity adjacent a second edge of the upper surface of the die; forming an underfill layer in the cavity between the lower surface of the die and the substrate; forming a fluid fan-out region by: depositing a curable material in the first space and the second space to form the fluid fan-out region, a surface of the fluid fan-out region being adjacent to the upper surface of the die; as well as forming a fluid flow channel over an active surface of the die, comprising: attaching a cap to a portion of the substrate adjacent the fluid fan-out region to form the fluid flow channel between the active surface and the cap; The method further comprises: coupling the exposed electrical contacts to the electrical contacts on the surface of the die; wherein the exposed electrical contacts and the electrical contacts on the surface of the die constitute bonding pads, wherein the bonding pads including the exposed electrical contacts are each oriented in one of the first space or the second space, and wherein the coupling comprises wire bonding each of the exposed electrical contacts to one of the electrical contacts on the surface of the die, thereby forming a wire bonding connection.

2. The method according to claim 1, further comprising: Prior to forming the fluid flow channel, the wire bond connections are encapsulated by depositing the curable material over the fluid fan-out region.

3. The method of claim 2, wherein forming the fluid flow channel over the active surface of the die further comprises: The cap is oriented in physical contact with a top surface of each of the encapsulated wire bonded connections, wherein the orientation flattens each top surface.

4. The method of claim 1 , wherein the die further comprises a silicon wafer, a passivation stack, and one or more through silicon vias extending through a portion of the silicon wafer and the passivation stack, wherein the passivation stack is disposed below a lower surface of the portion of the silicon wafer, wherein a portion of each of the one or more through silicon vias is exposed through one of the one or more openings in the passivation stack, and wherein each exposed portion is coupled to the electrical contact.

5. The method according to any one of claims 1 to 4, wherein the curable material is selected from epoxy resins and adhesives.

6. The method of any one of claims 1 to 4, wherein the forming a fluid fan-out region further comprises curing the curable material.

7. The method of claim 6, wherein the curing comprises utilizing a method selected from the group consisting of: exposing the curable material to ultraviolet radiation and exposing the curable material to thermal energy.

8. The method of any one of claims 1, 2, 3, 4, and 7, the die comprising a sensor.

9. The method of claim 8, wherein the sensor comprises a complementary metal oxide semiconductor (CMOS) detection device.

10. The method of any one of claims 1, 2, 3, 4, 7 and 9, wherein the chamber comprises: a die cavity portion, a fluid cavity portion, and a top-level portion, wherein the die cavity portion and the bottom fill layer together have a height substantially equal to that of the die, wherein the fluid cavity portion includes a space having a height of the fluid flow channel, and wherein the top-level portion has a height of the portion of the substrate adjacent to the fluid fan-out region. 11 . The method of claim 10 , wherein said placing the die in the portion of a cavity in a substrate comprises placing the die in the die cavity portion of the substrate.

12. The method of claim 10, wherein the portion of the substrate adjacent the fluid fan-out region comprises a portion of a circuit board, and wherein the top-level portion comprises an interface between the circuit board and the cover.

13. The method of any one of claims 1, 2, 3, 4, 7, 9, 11 and 12, wherein the closure comprises an inlet for a fluid and an outlet for a fluid.

14. The method of claim 12, wherein said attaching said cover comprises applying an adhesive between said circuit board and said cover.

15. The method of any one of claims 1, 2, 3, 4, 7, 9, 11, 12, and 14, wherein the die are singulated from a silicon wafer.

16. The method of any one of claims 1, 2, 3, 4, 7, 9, 11, 12 and 14, wherein the surface of the die is selected from: an upper surface of the die, a portion of the upper surface of the die including an active surface, and a lower surface parallel to the upper surface.

17. A bioassay device, comprising: a die, wherein one or more electrical contacts on a surface of the die are accessible; a substrate comprising a cavity, wherein the die is oriented in a portion of the cavity in the substrate, wherein the substrate comprises exposed electrical contacts electrically coupled to the electrical contacts on the surface of the die, wherein the orientation defines a first space in the cavity adjacent a first edge of an upper surface of the die and a second space in the cavity adjacent a second edge of the upper surface of the die; as well as a fluid fan-out region, the fluid fan-out region comprising a first solidified material deposited in the first space and the second space, a surface of the fluid fan-out region being adjacent to the upper surface of the die; wherein the exposed electrical contacts constitute substrate bond pads and the electrical contacts on the surface of the die constitute die bond pads, and wherein each die bond pad is coupled to at least one substrate bond pad with a wire to form a wire bond connection.

18. The apparatus according to claim 17, further comprising: A fluid flow channel over an active surface of the die is defined by the surface of the fluid fan-out region and the upper surface of the die and a cap attached to a portion of the substrate adjacent the fluid fan-out region.

19. The apparatus of claim 17 or 18, further comprising an underfill layer in the cavity between the lower surface of the die and the substrate.

20. The apparatus of any one of claims 17 and 18, wherein the dies are singulated from a silicon wafer.

21. The apparatus of claim 17, wherein the wire bond connections are encapsulated in a second cured material.

22. The apparatus according to claim 17, further comprising: A fluid flow channel above the active surface of the tube core, the fluid flow channel is defined by the surface of the fluid fan-out area and the upper surface of the tube core and a cap attached to a portion of the substrate adjacent to the fluid fan-out area, wherein the cap is oriented to physically contact the top surface of each of the packaged lead bonded connections.

23. The device of claim 21, wherein each of the first curable material and the second curable material is selected from the group consisting of: an epoxy resin and an adhesive.

24. The device of any one of claims 17, 18, 21, 22 and 23, wherein the die further comprises a silicon wafer, a passivation stack, and one or more through silicon vias extending through a portion of the silicon wafer and the passivation stack, wherein the passivation stack is disposed below a lower surface of the portion of the silicon wafer, wherein a portion of each of the one or more through silicon vias is exposed through one of the one or more openings in the passivation stack, and wherein each exposed portion is coupled to the electrical contact.

25. The apparatus of claim 24, wherein the electrical contacts of the die comprise stud bumps.

26. The device of any one of claims 17, 18, 21, 22, 23 and 25, the die comprising a sensor.

27. The apparatus of claim 26, wherein the sensor comprises a complementary metal oxide semiconductor (CMOS) detection device.

28. The apparatus according to claim 18, further comprising: a bottom fill layer in the cavity between the lower surface of the die and the substrate, wherein the cavity comprises: a die cavity portion, a fluid cavity portion, and a top portion, wherein the die cavity portion and the bottom fill layer together have a height substantially equal to that of the die, wherein the fluid cavity portion comprises a space having a height of the fluid flow channel, and wherein the top portion has a height of the portion of the substrate adjacent to the fluid fan-out region.

29. The apparatus of claim 28, wherein the portion of the cavity in the substrate in which the die is oriented comprises the die cavity portion.

30. The apparatus of claim 28 or 29, wherein the portion of the substrate adjacent the fluid fan-out region comprises a portion of a circuit board, and wherein the top-level portion comprises an interface between the circuit board and the cover.

31. The device of claim 18 or 22, wherein the cover comprises an inlet for fluid and an outlet for fluid.

32. The device of claim 18 or 22, wherein the fluid flow channel is approximately 100 μm from the active surface to the cover.

33. The device of claim 30, wherein the circuit board is selected from the group consisting of: a printed circuit board and a ceramic circuit board.

34. The device of any one of claims 17, 18, 21, 22, 23, 25, 27, 28, 29 and 33, wherein the surface is selected from: an upper surface of the tube core, a portion of the upper surface of the tube core including an active surface, and a lower surface parallel to the upper surface.

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