Fan-Out Flow Cell

Abstract

Various examples of flow cells and methods for forming embodiments of flow cells are provided herein. The method may include applying a first adhesive to a substrate. The method may include orienting a die onto the first adhesive. The method may also include orienting a package onto the first adhesive. The package includes a die, and a top surface of the die includes an active surface and electrical contacts. A surface adjacent to the active surface on at least two opposite sides of the active surface forms a fan-out region for use in a fluid path of the flow cell. The method may further include applying a second adhesive to a portion of the package and attaching a lid to the second adhesive to define a fluid flow cell cavity under the lid and above the surface including the active surface and the fan-out region.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS)

[0002] This PCT international patent application claims priority to U.S. Provisional Patent Application No. 63 / 146,444, entitled "Fanout Flow Cell," filed on February 5, 2021, and U.S. Provisional Patent Application No. 63 / 169,423, entitled "Fanout Flow Cell," filed on April 1, 2021, the entire contents of which are incorporated herein by reference. [Background technology]

[0003] Various protocols in biological or chemical research involve performing controlled reactions. The specified reactions can then be observed or detected, and subsequent analysis can help identify or reveal the properties of the chemicals involved in the reaction. In some multiplex assays, 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 deposited in a corresponding well of a microplate. Observing any chemical reactions that occur between the known probes and the unknown analyte in the well can help identify or reveal the properties of the analyte. Other examples of such protocols include known DNA sequencing processes, such as sequencing-by-synthesis (SBS) or circular array sequencing.

[0004] In some fluorescence detection protocols, optical systems are used to direct excitation light onto fluorophores, e.g., fluorescently labeled analytes, and to detect fluorescent emission signal light that may emanate from analytes to which fluorophores are attached. In other proposed detection systems, the controlled reactions in the flow cell are detected by solid-state optical sensor arrays (e.g., complementary metal oxide semiconductor (CMOS) detectors). These systems do not include large optical assemblies to detect fluorescent emissions. The shape of the fluid flow path in the flow cell can determine its usefulness for various applications, e.g., SBS or annular array sequencing is possible in sensor systems that utilize multiple liquid streams, and therefore, specific shapes of fluid flow paths are utilized for SBS or annular array sequencing.

[0005] To enable SBS in the optical systems described above, in some of the optical systems described, electrical contacts are provided to the sensor in the system (e.g., the CMOS utilized as a detector). In many such systems, a significant portion of the CMOS is occupied by the fluidic paths, minimizing the use of the sensor itself. To increase the size of the fluidic channels to increase the usability of the sensor, a region can be created around the sensor called a "fan-out" region. A fan-out region is an area packaged with the detector that extends a horizontal distance beyond the detector. For example, when a CMOS sensor is utilized as a detector in a flow cell, the fan-out refers to the additional horizontal distance on either side of the horizontal boundary of the CMOS sensor. Summary of the Invention

[0006] Forming a flow cell using a fan-out region can increase the availability of the sensor since the fan-out region assists the fluidic aspects of the flow cell, but in some situations and examples of flow cells, preparing the surface of the fan-out region to achieve the fluidic requirements of the cell can be difficult from a manufacturing and fabrication standpoint. For example, in some cases, preparing a surface to be used as a fan-out region can include a grinding procedure that can damage the surface if the material that makes up the surface is not sufficiently resistant to this process. This challenge can sometimes be understood when a ceramic substrate forms the fan-out region. In some situations, meeting the resistance requirements can lead to the selection of expensive materials, which can increase the costs associated with the flow cell. Therefore, it can be beneficial to exclude this grinding process in flow cell fabrication.

[0007] Thus, the shortcomings of the prior art may be overcome as described below in this disclosure, and benefits and advantages may be achieved through the provision of a method for forming a flow cell. Below, various examples of the method are described, including and excluding the additional examples listed below, which in any combination (if the combinations are not inconsistent) overcome these shortcomings. The method includes applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts, orienting a package on the first adhesive, the package including a die, the top surface of the die including an active surface and electrical contacts, and a surface adjacent to the active surface on at least two opposite sides of the active surface forming a fan-out region for use in a fluidic path of the flow cell, connecting the electrical contacts on the top surface of the substrate to the electrical contacts on the die, applying a second adhesive to a portion of the package, and attaching a lid to the second adhesive, the attaching defining a fluidic flow cell cavity under the lid and above the surface including the active surface and the fan-out region.

[0008] In some examples, the method includes forming a package, where forming the package includes orienting a die on a first adhesive and forming a fan-out region by orienting one or more support pieces on the first adhesive adjacent at least two sides of the die, the fan-out region including a portion of a top surface of the support pieces.

[0009] In some examples, the one or more support pieces include two support pieces, and orienting the one or more support pieces on the first adhesive adjacent to at least two sides of the die includes positioning the two support pieces adjacent to the die on either side of the die.

[0010] In some examples, the one or more support pieces include a single support piece, the single support piece including a notch, and orienting the one or more support pieces on the first adhesive adjacent to at least two sides of the die includes orienting the single support piece such that the die and the electrical contacts are within the notch.

[0011] In some examples, the package includes a hardened electronic molded compound (EMC) material molded around a portion of the die, where a portion of the EMC material includes the fan-out region.

[0012] In some examples of the method of forming a flow cell, forming the fan-out region further includes dispensing a material to fill a gap between the one or more support pieces and the die.

[0013] In some examples of methods of forming a flow cell, the one or more support pieces comprise a material selected from the group consisting of glass, silicon, and ceramic.

[0014] In some examples of methods of forming a flow cell, the package includes a cured electronic molding compound (EMC) material molded around a portion of the die and a layer deposited on a surface of the EMC material adjacent the active surface on at least two opposite sides of the active surface, and the fan-out region includes a portion of the layer.

[0015] In some examples of methods of forming a flow cell, the method includes forming a package that includes curing the EMC material around a portion of the die.

[0016] In some examples of the method of forming a flow cell, forming the package further includes planarizing a surface of the EMC material adjacent the active surface.

[0017] In some example methods of forming a flow cell, planarizing includes depositing a layer on a surface including the top surface of the die and an EMC material surface adjacent the active surface, opening the layer on the active surface, and curing the layer.

[0018] In some examples of methods for forming a flow cell, the layer comprises a photoresist.

[0019] In some examples of methods of forming a flow cell, the technique for opening the layers is selected from the group consisting of lithography and lithography plus lift-off.

[0020] In some examples of the method of forming a flow cell, the package further includes a via embedded in the EMC material.

[0021] In some examples of the method of forming the flow cell, forming the package further includes embedding vias in the EMC material before curing the EMC material around the portion of the die.

[0022] In some examples of methods of forming a flow cell, the vias are constructed from a conductive material.

[0023] In some examples of methods for forming a flow cell, the conductive material is selected from the group consisting of copper, gold, tungsten, and aluminum.

[0024] In some examples of methods of forming a flow cell, vias extend through the EMC material from a surface opposite the active surface in a direction opposite the active surface.

[0025] In some example methods of forming a flow cell, connecting electrical contacts on the top surface of the substrate to electrical contact points on the die includes wire bonding the electrical contacts to the electrical contact points.

[0026] In some examples of methods of forming a flow cell, the method includes encapsulating wire bonded connections with epoxy.

[0027] In some examples of the methods of forming a flow cell, the methods include curing the first adhesive and the second adhesive.

[0028] In some examples of methods of forming a flow cell, the curing is selected from the group consisting of thermal curing and ultraviolet (UV) curing.

[0029] In some examples of methods for forming a flow cell, the substrate is a printed circuit board.

[0030] In some examples of methods for forming a flow cell, the substrate comprises a material selected from the group consisting of glass reinforced epoxy laminate material, FR4, and co-fired ceramic sheets.

[0031] In some examples of the methods of forming a flow cell, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0032] In some examples of methods of forming a flow cell, the methods include forming a heating element in a substrate.

[0033] In some example methods of forming a flow cell, forming the heating element includes disposing one or more resistors on one or more of a top surface of the substrate and a bottom surface of the substrate, and coupling the one or more resistors to a metal plane in the substrate through a via.

[0034] Some example methods of forming a flow cell include forming a heating element in a substrate such that the heating element includes a long wound metal trace and acts as a resistive heater.

[0035] In some examples of the methods of forming a flow cell, applying the second adhesive further includes applying the second adhesive to a portion of the die.

[0036] In some examples of methods of forming a flow cell, the die is a complementary metal oxide semiconductor.

[0037] In some examples of methods of forming a flow cell, the lid includes two openings, each opening defining one of the inlet or outlet fluid ports.

[0038] In some examples of methods of forming a flow cell, the active surface of the die includes a nanowell.

[0039] The shortcomings of the prior art may be overcome as described below in this disclosure, and benefits and advantages may be achieved through the provision of a flow cell. Below, various examples of flow cells are described, including and excluding additional examples listed below, which in any combination (provided the combinations are not inconsistent) overcome these shortcomings. The flow cell includes a substrate including electrical contacts on a top surface thereof, the electrical contacts on the top surface of the substrate being connected to electrical contact points on a top surface of a die; a first cured adhesive bonded to a package, the package including a die, the top surface of the die further including an active surface, and a fan-out region including a surface adjacent at least two opposite sides of the active surface, the fan-out region at least partially defining a fluidic path of the flow cell; a second cured adhesive bonded to a portion of the top surface of the package to a lid to define a fluidic flow cell cavity below the lid and above the surface including the active surface and the fan-out region; and a lid.

[0040] In some examples of the flow cell, the package further includes one or more support pieces adjacent at least two opposing sides of the active surface of the die, the one or more support pieces including a fan-out region.

[0041] In some examples of the flow cell, the one or more support pieces include two support pieces oriented on at least two opposite sides of the active surface of the die.

[0042] In some examples of the flow cell, the one or more support pieces include a support piece, the support piece including a notch, and the die and electrical contacts on the top surface of the substrate are oriented within the notch.

[0043] In some examples of the flow cell, the package further includes a cured electronic molding compound (EMC) material molded around a portion of the die and a portion of the EMC material forming an EMC material surface adjacent the active surface on at least two opposing sides of the active surface, the portion of the EMC material surface including a fan-out region.

[0044] In some examples of the flow cell, the package includes a cured electronic molding compound (EMC) material molded around a portion of the die, and a layer deposited on a surface of the EMC material adjacent the active surface on at least two opposite sides of the active surface, the fan-out region including a portion of the layer.

[0045] In some examples of the flow cell, the package further includes vias embedded in the EMC material.

[0046] In some examples of the flow cell, the one or more support pieces comprise a material selected from the group consisting of glass, silicon, and ceramic.

[0047] In some examples of the flow cell, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0048] In some examples of the flow cell, the substrate further includes a heating element.

[0049] In some examples of the flow cell, the heating element includes one or more resistors on one or more of the top surface of the substrate and the bottom surface of the substrate, a metal plane in the substrate, and a via through the substrate coupling the one or more resistors in the substrate to the metal plane.

[0050] In some examples of flow cells, the heating element comprises a long wound metal trace within a substrate to function as a resistive heater.

[0051] In some examples of the flow cell, the lid includes two openings, each opening defining one of the inlet or outlet fluid ports.

[0052] In some examples of the flow cell, the top surface of the die contains nanowells.

[0053] In some examples of flow cells, the substrate is a printed circuit board.

[0054] In some examples of the flow cell, the substrate comprises a material selected from the group consisting of a glass reinforced epoxy laminate material, FR4, and a co-fired ceramic sheet.

[0055] In some examples of the flow cell, the die is a complementary metal oxide semiconductor.

[0056] In some examples of the flow cell, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0057] The shortcomings of the prior art may be overcome as described below in this disclosure, and benefits and advantages may be achieved through the provision of a method for forming a flow cell. Below, various examples of the method are described, which, in any combination (provided that the combination is not inconsistent), overcome these shortcomings, including and excluding the additional examples listed below. The method includes applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts; orienting a die on the first adhesive, the top surface of the die including an active surface and electrical contact points; forming a fan-out region for use in a fluidic path of a flow cell, the forming of the fan-out region including orienting one or more support pieces on the first adhesive adjacent at least two sides of the die, the support pieces on at least two sides of the die including a portion of the top surface of the support pieces including the fan-out region; connecting electrical contacts on the top surface of the substrate to the electrical contact points on the die; applying a second adhesive to a portion of the one or more support pieces; and attaching a lid to the second adhesive, the attaching defining a fluidic flow cell cavity below the lid and above a surface including the active surface and the fan-out region.

[0058] In some examples, the one or more support pieces include two support pieces, and orienting the one or more support pieces on the first adhesive adjacent at least two sides of the die includes positioning the two support pieces adjacent both sides of the die.

[0059] In some examples, the one or more support pieces include a single support piece, the single support piece including a notch, and orienting the one or more support pieces on the first adhesive adjacent to at least two sides of the die includes orienting the single support piece such that the die and the electrical contacts are within the notch.

[0060] In some examples, the method also includes securing the wire bonded connections with epoxy.

[0061] In some examples, forming the heating element includes mounting long winding metal traces within the substrate to act as resistive heaters.

[0062] In some examples, the method further includes heating the substrate utilizing a heating element.

[0063] The shortcomings of the prior art may be overcome, and benefits and advantages may be achieved through the provision of a flow cell, as described below in this disclosure. Below, various examples of flow cells are described, including and excluding the additional examples listed below, which, in any combination (provided that such combinations are not inconsistent), overcome these shortcomings. The flow cell includes a substrate including electrical contacts on a top surface thereof, the electrical contacts on the top surface of the substrate being connected to electrical contact points on the top surface of the die; a first cured adhesive that bonds the die and one or more support pieces adjacent at least two sides of the die to the substrate, with a portion of the top surface of the die and a portion of the top surface of the one or more support pieces forming a surface utilized in the fluid path of the flow cell; a second cured adhesive that bonds an area of ​​the one or more support pieces and an area of ​​the top surface of the die adjacent to the surface utilized in the fluid path of the flow cell to a lid; and a lid that defines a fluidic flow cell cavity above the surface utilized in the fluid path of the flow cell and below the lid.

[0064] In some examples of flow cells, the one or more support pieces include two support pieces oriented on either side of the die.

[0065] In some examples of the flow cell, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0066] The shortcomings of the prior art may be overcome as described below in this disclosure, and benefits and advantages may be achieved through the provision of a method for forming a flow cell. Below, various examples of the method are described, which, in any combination (provided that the combination is not inconsistent), overcome these shortcomings, including and excluding the additional examples listed below. The method includes applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts; orienting a die on the first adhesive, the top surface of the die including an active surface and electrical contact points; forming a fan-out region for use in a fluid path of a flow cell, the forming of the fan-out region including: orienting two support pieces on the first adhesive on either side of the die, each of the two support pieces being adjacent to the die, the top surface of the die and the top surfaces of the two support pieces forming a top surface; and dispensing material to fill gaps between the two support pieces and the die; connecting the electrical contacts on the top surface of the substrate to the electrical contact points on the die; applying a second adhesive to a portion of one or more support pieces and a portion of the die; and attaching a lid to the second adhesive, the attaching defining a fluidic flow cell cavity below the lid and above the top surface.

[0067] The shortcomings of the prior art may be overcome as described below in this disclosure, and benefits and advantages may be achieved through the provision of a method for forming a flow cell. Below, various examples of the method are described, including and excluding additional examples listed below, which in any combination (provided the combination is not inconsistent) overcome these shortcomings. The method includes applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts, orienting a die on the first adhesive, the top surface of the die including an active surface and electrical contacts, and forming a fan-out region for use in a fluid path of the flow cell, the forming the fan-out region including orienting a support piece on the first adhesive, the support piece including a notch, and the orienting includes placing the support piece on the first adhesive such that the die and electrical contacts are positioned within the notch, the fan-out region including a die on either side of the die. forming a substrate including a portion of a top surface of the support piece, the portion of the top surface and the active surface forming a top surface; connecting electrical contacts on the top surface of the substrate to electrical contact points on the die with bond wires; and dispensing a second adhesive into the notches such that the second adhesive fills a space in the notches between the die and the support piece and encapsulates the bond wires; applying a third adhesive to a portion of the support piece and a portion of the die; and attaching a lid to the third adhesive, the attaching defining a fluid flow cell cavity below the lid and above the top surface.

[0068] The shortcomings of the prior art may be overcome as described below in this disclosure, and benefits and advantages may be achieved through the provision of a method for forming a flow cell. Below, various examples of the method are described, which, in any combination (provided that the combination is not inconsistent), overcome these shortcomings, including and excluding the additional examples listed below. The method includes applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts; orienting a package including a cured electronic molding compound (EMC) material molded around a portion of a die, the top surface of the die including an active surface and electrical contacts, a portion of the EMC material forming an EMC material surface adjacent to the active surface on at least two opposite sides of the active surface; connecting the electrical contacts on the top surface of the substrate to the electrical contacts on the die; applying a second adhesive to a portion of the top surface of the package; and attaching a lid to the second adhesive, the attaching defining a fluid flow cell cavity beneath the lid and above a surface including the active surface and a fan-out region for utilization in a fluid path of the flow cell, the fan-out region including another portion of the top surface of the package.

[0069] In some examples, the fan-out region is comprised of EMC material surfaces adjacent to the active surface on at least two opposing sides of the active surface.

[0070] In some examples, the package further includes a layer deposited on the EMC material surface adjacent the active surface on at least two opposite sides of the active surface, and the fan-out region includes a portion of the layer deposited on the EMC material surface adjacent the active surface on at least two opposite sides of the active surface.

[0071] In some examples, connecting the electrical contacts on the top surface of the substrate to the electrical contact points on the die includes wire bonding the electrical contacts to the electrical contact points.

[0072] In some examples, the method includes securing the wire bonded connections with epoxy.

[0073] In some examples, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0074] In some examples, the method further includes forming a package, where forming the package includes curing the EMC material around a portion of the die.

[0075] The shortcomings of the prior art may be overcome, and benefits and advantages may be achieved through the provision of a flow cell, as described below in this disclosure. Below, various examples of flow cells are described, including and excluding the additional examples listed below, which, in any combination (provided that the combinations are not inconsistent), overcome these shortcomings. The flow cell includes a substrate including electrical contacts on a top surface thereof, the electrical contacts on the top surface of the substrate being connected to electrical contact points on a top surface of a die; a first curing adhesive that bonds a package including a cured electronic molding compound (EMC) material molded around a portion of the die, the top surface of the die being exposed and including an active surface and electrical contact points, a portion of the EMC material forming an EMC material surface adjacent the active surface on at least two opposite sides of the active surface, the portion of the EMC material surface including a fan-out region for use in a fluid path; a second curing adhesive that bonds a portion of the top surface of the package to a lid to define a fluid flow cell cavity below the lid and above the surface including the active surface and the fan-out region; and a lid.

[0076] In some examples, the substrate is a printed circuit board and the die is a complementary metal oxide semiconductor.

[0077] The shortcomings of the prior art may be overcome, and benefits and advantages may be achieved through the provision of a flow cell, as described below in this disclosure. Below, various examples of flow cells are described, including and excluding the additional examples listed below, which, in any combination (provided that such combinations are not inconsistent), overcome these shortcomings. The flow cell includes a substrate including electrical contacts on a top surface thereof, the electrical contacts on the top surface of the substrate being connected to electrical contact points on a top surface of a die; a first curing adhesive that bonds a package including a cured electronic molding compound (EMC) material molded around a portion of the die, the top surface of the die being exposed and including an active surface and electrical contact points, a portion of the EMC material forming an EMC material surface adjacent to the active surface on at least two opposite sides of the active surface, a layer planarizing the EMC material surface, the portion of the EMC material surface planarized by the layer including a fan-out region for utilization in a fluid path; a second curing adhesive that bonds a portion of the top surface of the package to a lid to define a fluid flow cell cavity below the lid and above the surface including the active surface and the fan-out region; and a lid.

[0078] The shortcomings of the prior art may be overcome as described below in this disclosure, and benefits and advantages may be achieved through the provision of a method for forming an element that can be used in one or more flow cells. Below, various examples of the method are described, which, in any combination (provided that the combination is not inconsistent), overcome these shortcomings, including and excluding the additional examples listed below. The method includes assembling a package including a hardened molding material surrounding a portion of the one or more dies, wherein one or more pillars of a first conductive material are embedded in the molding material, and assembling includes applying a temporary adhesive to a surface of the carrier, orienting the one or more pillars on the adhesive, orienting the one or more dies on the adhesive such that the one or more pillars are oriented between each of the one or more dies, wherein each of the one or more pillars is of a greater vertical length than each of the one or more dies, molding material around a top surface of the carrier and a surface of the one or more dies and a portion of the one or more pillars such that a top surface of the mold is of a greater vertical length than the one or more pillars, wherein the top surface of the mold is parallel to a surface of the carrier, molding, hardening the molding material, grinding a top surface of the mold to expose top surfaces of the one or more pillars and top surfaces of the one or more dies to create a new surface, plating the top surfaces of the one or more pillars with a second conductive material to create a seed layer, and forming one or more redistribution layers. applying a seed layer (RDL) of one or more RDLs, where applying each RDL includes patterning the layer over the new surface, opening a portion of the layer to form an opening, and spreading the third conductive material into each opening such that the third conductive material spreads through the opening and is electrically coupled to the seed layer; applying electrical contacts to a portion of the third conductive material in the opening of the RDL of one or more RDLs; and removing the carrier and temporary adhesive to expose the package surface.

[0079] In some examples, the method includes applying a surface chemical to a surface of one or more die exposed by removing the carrier and temporary adhesive to create an active surface, and plating a surface of one or more pillars exposed by removing the carrier and temporary adhesive to create electrical contacts on the pillars.

[0080] In some examples, the method includes electrically coupling electrical contacts on the pillars to portions of a surface of the one or more dies that include the chemical.

[0081] In some examples, the method of electrically coupling the electrical contacts on the pillars to the portions of the surface of the one or more dies that contain the chemicals is selected from the group consisting of wirebonding and printing.

[0082] In some examples, the method includes attaching one or more lids to a package surface, wherein a fluid flow cell cavity is defined beneath each of the one or more lids and above a surface of each of the one or more corresponding sensors that includes an active surface.

[0083] In some examples, the first conductive material and the third conductive material are copper.

[0084] In some examples, the second conductive material includes one or more of nickel and gold.

[0085] In some examples, attaching the one or more lids includes applying an adhesive to a portion of a surface of the package.

[0086] In some examples, opening portions of the layer to form openings includes using photolithography.

[0087] In some examples, the one or more RDLs include three RDLs.

[0088] In some examples, orienting the one or more pillars and orienting the one or more die includes utilizing a pick-and-place tool.

[0089] In some examples, the molding material includes an electronic molding compound (EMC) material.

[0090] The shortcomings of the prior art may be overcome as described below in this disclosure, and benefits and advantages may be achieved through the provision of a flow cell. Below, various examples of flow cells are described, including and excluding additional examples listed below, which in any combination (provided the combinations are not inconsistent) overcome these shortcomings. The flow cell includes a package including a hardened material molded around a portion of a die, where one or more pillars of a first conductive material are embedded in the molding material, and where a top surface of the package includes an active surface of the die, and a lid attached to a portion of the top surface of the package, where a fluid flow cell cavity is defined below the lid and above the active surface.

[0091] In some examples, the package includes one or more redistribution layers (RDLs) attached to a bottom surface of the package, the RDLs including openings filled with a conductive material electrically coupled to at least one of the one or more pillars.

[0092] In some examples, the package includes electrical contacts electrically coupled to the conductive material in the openings of the one or more RDLs.

[0093] In some examples, the curable material includes an electronic molding compound (EMC).

[0094] Additional features are realized through the techniques described herein. Other examples and aspects are described in detail herein and are considered a part of the claimed aspects. These and other objects, features, and advantages of the present disclosure will become apparent from the following detailed description of the various aspects of the disclosure taken in conjunction with the accompanying drawings.

[0095] It is to be understood that all combinations of the foregoing embodiments and additional concepts discussed in more detail herein (provided such concepts are not mutually inconsistent) are considered to be part of the inventive subject matter and to achieve the advantages disclosed herein. [Brief description of the drawings]

[0096] One or more aspects are particularly pointed out and distinctly claimed as examples at the conclusion of the specification. The foregoing as well as the objects, features, and advantages of one or more aspects will become apparent from the following detailed description taken in conjunction with the accompanying drawings. [Figure 1] 1A and 1B show assembled and exploded views, respectively, of a flow cell having a fan-out region, the fan-out region being formed by assembling a sensor or detector onto a substrate using one or more support pieces. [Diagram 2] 1A and 1B show assembled and exploded views, respectively, of a flow cell having a fan-out region, the fan-out region being formed by assembling a sensor or detector onto a substrate using one or more support pieces. [Diagram 3] 1 and 2 are top and bottom views of the flow cells shown in FIG. 1 and FIG. 2, respectively. [Figure 4] 1 and 2 are top and bottom views of the flow cells shown in FIG. 1 and FIG. 2, respectively. [Diagram 5] 4 is a process flow illustrating the step-by-step formation of the flow cell of FIGS. 1 and 3. [Figure 6] 4 is a workflow illustrating a method of forming the flow cell of FIGS. 1 and 3. [Figure 7] 5 is a process flow illustrating the step-by-step formation of the flow cell of FIGS. 2 and 4. [Figure 8] 5 is a workflow illustrating a method of forming the flow cell of FIGS. 2 and 4. [Figure 9] FIG. 1 shows a side view of an example of a flow cell, illustrating a heating element that may be integrated into the examples discussed herein. [Figure 10]1A and 1B show assembled and exploded views, respectively, of a flow cell including a package that includes a material molded around a sensor or detector. [Figure 11] 1A and 1B show assembled and exploded views, respectively, of a flow cell including a package that includes a material molded around a sensor or detector. [Figure 12] 12 shows a side view of one of the packages shown in FIGS. 10-11, respectively. [Figure 13] 12 shows a side view of one of the packages shown in FIGS. 10-11, respectively. [Figure 14] 10 and 11 show top and bottom views of the flow cells shown in the figures, respectively. [Figure 15] 10 and 11 show top and bottom views of the flow cells shown in the figures, respectively. [Figure 16] 15 is a process flow illustrating the step-by-step formation of the flow cell of FIGS. 10 and 14. [Figure 17] 15 is a workflow illustrating a method of forming the flow cell of FIGS. 10 and 14. [Figure 18] 16 is a process flow illustrating the step-by-step formation of the flow cell of FIGS. 11 and 15. [Figure 19] 16 is a workflow illustrating a method of forming the flow cell of FIGS. 11 and 15. [Figure 20] FIG. 13 shows a side view of an example of a flow cell having the elements of the flow cell shown in FIGS. 10-11 and 14-15, specifically illustrating a heating element that may be integrated into the examples discussed herein. [Figure 21] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Figure 22] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Figure 23] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Figure 24] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Diagram 25] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Figure 26] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Figure 27] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Figure 28] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Figure 29] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Diagram 30] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Diagram 31] 1 shows a process flow illustrating the step-by-step formation of a flow cell including certain embodiments of packaging shown in the flow cells of FIGS. 10-11 and 14-15. [Diagram 32] 32 is a workflow illustrating a method of forming the flow cell of FIG. 31. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0097] The accompanying drawings, in which like reference numbers refer to the same or functionally similar elements throughout the different views and which are incorporated in and form a part of this specification, further illustrate the present implementations and, together with the detailed description of the implementations, serve to explain the principles of the present implementations. As will be appreciated by those skilled in the art, the accompanying drawings are provided for ease of understanding and illustrate certain example aspects of the present implementations. The implementations are not limited to the examples depicted in the drawings.

[0098] The terms "connect," "connected," "contact," "coupled," and the like are broadly defined herein to include a variety of different arrangements and assembly techniques, including, but not limited to, (1) directly joining one component to another without any intervening components between them (i.e., the components are in direct physical contact), and (2) connecting one component to another with one or more components between them, provided that a component that is "connected" or "in contact" or "coupled" to another component is in some operative communication (e.g., electrical, fluid, physical, optical, etc.) with the other component (notwithstanding the presence of one or more additional components between them). 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 fluid contact with each other. Furthermore, two components that are electrically connected, electrically coupled, optically connected, optically coupled, fluidly connected, or fluidly coupled may or may not be in direct physical contact, and one or more other components may be located between them.

[0099] As used herein, the terms "including" and "comprising" mean the same thing.

[0100] The terms "substantially," "approximately," "about," "relatively," or other such similar terms, which may be used throughout this disclosure, including the claims, are used to describe and take into account small variations from a reference or parameter, such as due to variations in processing. Such small variations also include zero-point variations from a reference or parameter. For example, they can refer to ±10% or less, such as ±5% or less, such as ±2% or less, such as ±1% or less, such as ±0.5% or less, such as ±0.2% or less, such as ±0.1% or less, such as ±0.05% or less. As used herein, "substantially," "approximately," "about," "relatively," or other such similar terms can also refer to no variation, i.e., ±0%.

[0101] As used herein, a "flow cell" can include a device having a lid extending over a reaction structure forming a flow channel therebetween in communication with multiple reaction sites of the reaction structure, and can include a detection device for detecting a specified reaction occurring at or near the reaction sites. The flow cell can include a solid-state physics light detection or "imaging" device, such as a charge-coupled device (CCD) or a complementary metal oxide semiconductor (CMOS) (light) detection device. As one specific example, the flow cell can be fluidly and electrically coupled to a cartridge (with an integrated pump) that can be fluidly and / or electrically coupled to a bioassay system. The cartridge and / or bioassay system can deliver reaction solutions to the reaction sites of the flow cell according to a predetermined protocol (e.g., sequencing by synthesis) and perform multiple imaging events. For example, the cartridge and / or bioassay system can direct one or more reaction solutions through the flow channel of the flow cell and thereby along the reaction sites. At least one of the reaction solutions can include four types of nucleotides with the same or different fluorescent labels. In some examples, the nucleotides bind to reaction sites of the flow cell, such as corresponding oligonucleotides of the reaction sites. In these examples, the cartridge and / or bioassay system then illuminates the reaction sites 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 a predetermined wavelength or multiple wavelengths, including a range of wavelengths. Fluorescent labels excited by the incident excitation light can provide emission signals (e.g., light of one or more wavelengths different from the excitation light, and potentially different from each other) that can be detected by a light sensor of the flow cell.

[0102] The flow cells described herein perform a variety of biological or chemical processes. More specifically, the flow cells described herein can be used in a variety of processes and systems in which it is desirable to detect an event, property, quality, or characteristic indicative of a specified reaction. For example, the flow cells described herein can include or be integrated with optical detection devices, sensors, including but not limited to biosensors, and components thereof, as well as bioassay systems that operate in conjunction with sensors, including biosensors.

[0103] The flow cell facilitates multiple designated reactions that can be detected individually or collectively. The flow cell executes multiple cycles in which multiple designated reactions occur in parallel. For example, the flow cell can be used to sequence a high-density array of DNA features through repeated cycles of enzymatic operation and light or image detection / capture. Thus, the flow cell can be in fluid communication with one or more microfluidic channels that deliver reagents or other reaction components in a reaction solution to reaction sites of the flow cell. The reaction sites can be provided or spaced in a predetermined manner, such as in a uniform or repeating pattern. Alternatively, the reaction sites can be randomly distributed. Each of the reaction sites 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 to filter specific wavelengths of light. The light guide can be, for example, an absorptive filter (e.g., an organic absorptive filter) such that the filter material absorbs a specific wavelength (or range of wavelengths) and allows at least one predetermined wavelength (or range of wavelengths) to pass therethrough. In some flow cells, the reaction sites may be located within a reaction recess or chamber within which a designated reaction may be at least partially compartmentalized.

[0104] As used herein, a "designated reaction" includes a change in at least one of the chemical, electrical, physical, or optical properties (or qualities) of a chemical or biological substance of interest, such as an analyte of interest. In certain flow cells, the designated reaction is a positive binding event, such as the incorporation of a fluorescently labeled biomolecule with the analyte of interest. More generally, the designated reaction may be a chemical conversion, chemical change, or chemical interaction. The designated reaction may also be a change in an electrical property. In certain flow cells, the designated reaction includes the incorporation of a fluorescently labeled molecule with an analyte. The analyte may be an oligonucleotide, and the fluorescently labeled molecule may be a nucleotide. The designated reaction may be detected when excitation light is directed at the oligonucleotide with the 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. The specified reaction can also, for example, increase Fluorescence (or Forster) Resonance Energy Transfer (FRET) by bringing a donor fluorophore into close proximity to an acceptor fluorophore, decrease FRET by separating the donor and acceptor fluorophores, increase fluorescence by separating a quencher from a fluorophore, or decrease fluorescence by colocalizing a quencher and a fluorophore.

[0105] 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 a substrate, droplets, conductive traces, wires, waveguides, nanostructures, other circuit segments, etc. The terms "electrically coupled" and "optically coupled" may be used in reference to direct or indirect connections that may pass through various media, such as fluid media, air gaps, etc.

[0106] As used herein, a "reaction solution," "reaction component," or "reactant" includes any material that can be used to obtain at least one specified reaction. For example, potential reaction components include, for example, reagents, enzymes, samples, other biomolecules, and buffers. A reaction component can be delivered in solution to a reaction site in a flow cell disclosed herein and / or can be immobilized at a reaction site. A reaction component can directly or indirectly interact with another material, such as an analyte of interest, immobilized at a reaction site of a flow cell.

[0107] As used herein, the term "reaction site" is a localized area where at least one designated reaction can occur. A reaction site may include a support surface of a reaction structure or substrate on which a substance can be immobilized. For example, a reaction site may include a surface of a reaction structure (which may be positioned within a channel of a flow cell) having reaction components thereon, such as a colony of nucleic acid thereon. In some flow cells, the nucleic acids in the colony have the same sequence, e.g., are clonal copies of a single-stranded or double-stranded template. However, in some flow cells, a reaction site may only include a single nucleic acid molecule, e.g., in single-stranded or double-stranded form.

[0108] The term "active surface" is used herein to characterize the horizontal surface of a sensor or detector that operates as a sensor or detector in a package. For example, in an example where a CMOS sensor is utilized as a detector in a flow cell, the active surface is the portion of the surface of the CMOS sensor that includes the nanowells. Throughout this disclosure, the terms die and wafer are also used in connection with certain examples herein, since a die may include a sensor and a die may be fabricated from a wafer.

[0109] The term "fan-out" is used herein to characterize the area packaged with a detector that extends a horizontal distance beyond the detector. For example, if a CMOS sensor is utilized as the detector for a flow cell, the fan-out refers to the additional horizontal distance on either side of the horizontal boundary of the CMOS sensor.

[0110] As used herein, the terms "pillar bump" and "bump" are both used to describe electrical contacts in the examples shown and described herein. When the terms "pillar bump" or "bump" are utilized, various examples of electrical contacts may also be utilized in the various examples of devices illustrated herein. The electrical contacts, which may be pillar bumps or bumps, may include a conductive material such as a metallic material (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum), or combinations thereof), although it is understood that other conductive materials may be utilized.

[0111] For ease of understanding, reference is made below to the drawings, which are not drawn to scale and the same reference numbers are used throughout different figures to denote the same or similar components.

[0112] In some flow cells, a large portion of the active surface of the sensor or detector (e.g., CMOS) is sometimes occupied by fluid, and thus the active surface, the sensor area itself, may be underutilized. Flow cells may be formed with fan-out regions so that the entire surface of the sensor may be more efficiently and more fully utilized as a sensor or detector to move some of the fluidic functions away from the active surface. However, certain techniques for forming the fan-out regions may contribute to the complexity associated with forming the flow cells as well as increasing the cost. These techniques may also impose certain limitations on the type of materials that may be used to form these fan-out regions in certain examples. For example, in some flow cells, a grinding process is used for the fan-out regions, and expensive substrates (or carriers) may be utilized to withstand this process. The examples described herein describe methods for forming flow cells, and the resulting flow cells are formed by utilizing materials (e.g., glass, silicon, ceramic, etc.) utilized for printed circuit boards (PCBs) as substrates, which are generally understood to be less expensive materials than those utilized in the examples including the grinding process described above.

[0113] The examples described herein do not utilize the grinding process described above, but allow for variation in the material of the substrate. In the examples herein, the fan-out region is formed by assembling the sensor or detector on the substrate, as shown in the figures below. In these examples, the fan-out region itself is formed by various methods, including, but not limited to: 1) assembling a support piece (e.g., glass, silicon, and ceramic) on the substrate, with a portion of the support piece forming the fan-out region, and / or 2) packaging the sensor (e.g., CMOS image sensor die) by molding an electronic molding compound (EMC) material (epoxy mold compound) around it, with a portion of the EMC material forming the fan-out region. In the latter examples, the EMC molded around the die may or may not be embedded with vias (e.g., copper vias) for thermal conduction. In these examples, the substrate is a PCB. In some examples, the PCB substrate may be embedded with a built-in heating mechanism, as shown herein, which is accomplished utilizing at least two methods, including but not limited to: 1) implementing a heat spreading plane by placing power resistors on one or more of the top or bottom of the PCB substrate such that heat is carried to the desired location by vias (e.g., conductive vias, metallic vias, etc.) to a metal plate within the substrate, where the (now) heated metal plate spreads the heat to maintain a uniform and / or near uniform temperature distribution at the desired location, and / or 2) implementing resistive paths by utilizing interconnects within the PCB as heat sources by embedding or otherwise implementing traces (e.g., long windings) at the desired locations to generate heat through the resistance of each path. In various examples, the spreading plane and / or resistive paths may be separated into different zones on the substrate such that the substrate includes different temperature zones, which may be individually tuned.

[0114] Described herein are various examples of flow cells utilizing support pieces as fan-out regions and methods of forming these flow cells, as well as various examples of flow cells utilizing EMC material as fan-out regions and methods of forming these flow cells. Figures 1-9 show various elements and aspects of example flow cells formed by assembling a sensor or detector onto a substrate PCB using support pieces. Figures 10-20 show various elements and aspects of example flow cells formed by assembling a package including a sensor or detector and EMC material onto a substrate PCB, and Figures 21-32 show the formation of several example EMC and sensor or detector packages that may be included in the flow cells at least partially described in Figures 10-20.

[0115] Referring first to examples including one or more support pieces, FIGS. 1-2 each include assembled and exploded views of a flow cell 100, 200 having a fan-out region formed by utilizing support pieces and assembling a sensor or detector onto a substrate PCB. FIGS. 3-4 each provide a top and bottom view of the flow cell 100, 200 shown in FIGS. 1-2. These figures, FIGS. 1-4, are included to provide an overview of certain elements of the structure of various examples of flow cells 100, 200 that may be formed utilizing the methods described herein. FIGS. 5-8 illustrate these methods in more detail. Specifically, FIG. 5 is a process flow 500 illustrating the step-by-step formation of the flow cell 100 of FIG. 1 (and FIG. 3). FIG. 6 is a workflow 600 that repeats various aspects of FIG. 5, but without an illustration of the flow cell 100 itself. FIG. 7 is a process flow 700 illustrating the step-by-step formation of the flow cell 200 of FIG. 2 (and FIG. 4). Similar to Figure 6, Figure 8 is a workflow 800 reviewing aspects of the formation of a flow cell, including flow cell 200 of Figure 2 (and Figure 4), without illustration of these aspects. Figure 9 provides a side view of an example flow cell to show a heating element that may be integrated into the examples discussed herein.

[0116] Referring first to FIG. 1, included in this figure are two views of the flow cell 100, an assembled view 125 on the left, and an exploded view 135 on the right. As shown in this example, a detector or sensor (e.g., CMOS) 180 is attached to a PCB substrate 150. In some examples, the detector or sensor 180 is a CMOS image sensor with nanowell structures patterned on it (e.g., on the active surface). The PCB substrate 150 may be constructed from standard PCB laminate materials, including but not limited to glass reinforced epoxy laminate materials such as FR4 and / or co-fired ceramic sheets. In some examples, the PCB substrate 150 includes a built-in heater (not shown). As evident in the exploded view 135, the detector or sensor (e.g., CMOS) 180 is attached to the PCB substrate 150 using a film or adhesive 140, which in turn attaches support pieces 130 to either side of the detector or sensor (e.g., CMOS) 180 to form a fan-out region. In some examples, the adhesive is dispensed and / or applied as a film that attaches the detector or sensor 180 and adjacent support pieces 130 to the substrate 150. The film or adhesive 140 may be heat cured and / or ultraviolet (UV) cured. Materials that may comprise these support pieces 130 may include, but are not limited to, glass, silicon, and ceramic. Another film or adhesive 120 is used to attach the lid (e.g., glass) 110. The film or adhesive 120 may be dispensed or formed as a film to attach the lid 110 to the detector or sensor 180 (e.g., CMOS die) and fan-out support pieces 130. The space below the lid 110 and above the active (top) surface of the detector or sensor (e.g., CMOS) 180 and the top surface of portions of the support pieces 130 (not covered by the film or adhesive 120) form a flow path. The lid 110 defines a fluidic flow cell cavity with inlet and outlet fluid ports 105. Contacts (not shown) on the active surface of a detector or sensor (eg, CMOS) 180 are wire bonded 170 to electrical connections (eg, bond pads, contact pads) 160 on the PCB substrate 150 .In some examples, the electrical connections 160 are metal bond pads on the top surface of the PCB substrate 150, allowing wire bonding to bond pads on the top surface of the detector or sensor 180 (eg, a CMOS die).

[0117] As seen in FIG. 2, the difference between the flow cell 100 of FIG. 1 and the flow cell 200 of FIG. 2 is that in FIG. 2, a single support piece 230 is utilized to form a fan-out region on both sides of the detector or sensor (e.g., CMOS) 280. In some examples, the detector or sensor 280 is a CMOS image sensor with nanowell structures patterned on top (e.g., on the active surface). To accommodate the difference in the support structure 230 used to form the fan-out region, the film or adhesive 240 used to attach the detector or sensor (e.g., CMOS) 280 to the PCB substrate is shaped differently. As is more evident in the exploded view 235, the detector or sensor (e.g., CMOS) 280 is attached to the PCB substrate 250, which may include a built-in heater (not shown), using the film or adhesive 240. The PCB substrate 150 may be constructed from standard PCB laminate materials, including but not limited to glass-reinforced epoxy laminate materials such as FR4 and / or co-fired ceramic sheets. The film or adhesive 240 is also used to attach the support piece 230 that surrounds the detector or sensor (e.g., CMOS) 280. The support piece 280 includes a cutout 265 that accommodates the detector or sensor (e.g., CMOS) 280, as well as electrical connections (e.g., bond pads, contact pads) 260 on the PCB substrate 250. The electrical connections (e.g., bond pads, contact pads) 260 are wire bonded to electrical contacts (not shown) of the detector or sensor (e.g., CMOS) 280. In some examples, the electrical connections 260 are metal bond pads on the top surface of the PCB substrate 250 that allow wire bonding to bond pads on the top surface of the detector or sensor 280 (e.g., CMOS die). The support piece 230 can be constructed of materials including, but not limited to, glass, silicon, and ceramic. Another film or adhesive 220 is used to attach the lid (e.g., glass) 210. This film or adhesive 220 can be dispensed or formed as a film to attach the lid 210 to the detector or sensor 280 (eg, a CMOS die) and the fan-out support pieces 230 .The space below the lid and above the active (top) surface of the detector or sensor (e.g., CMOS) 280 and the top surface of the portion of the support piece 230 (not covered by the film or adhesive 220 or covered by the lid 210) forms the flow path. The lid 210 also defines a fluidic flow cell cavity having inlet and outlet fluid ports 205.

[0118] FIG. 3 shows a top view 145 and a bottom view 155 of the flow cell 100. The flow cell 100 is also shown in FIG. 1. The bottom view 155 of the flow cell 100, specifically the substrate 150, shows electrical contacts 167, which may include pads (called pogo pads) that include pogo pins. These electrical contacts 167 allow electrical connection to a receiving socket and / or instrumentation of the flow cell 100 (specifically, ultimately, the detector or sensor 180). As shown in later figures, vias and / or various other conductive elements formed throughout the PCB substrate 150 connect the electrical contacts 160 to the electrical contacts 167. As previously mentioned, the electrical contacts 160 are wire bonded to bond pads on the top surface of the detector or sensor 180 (e.g., a CMOS die). Visible from the top view 145 of the lid 110 (which in this example is translucent and may be made of glass) are the inlet and outlet fluid ports 105. Beneath the lid 110 is a fan-out region formed as shown in FIG. 1, with support pieces 130, not visible from any of the views in FIG.

[0119] Referring to FIG. 4, FIG. 4 shows a top view 245 and a bottom view 255 of a flow cell 200, which is also shown in FIG. 2. The bottom view 255 of the flow cell 200, specifically the substrate, shows electrical contacts 267, which may include pads (called pogo pads) that include pogo pins. These electrical contacts 267 allow electrical connection of the flow cell 200 (specifically the detector or sensor 280) to a receiving socket and / or instrumentation. As shown in later figures, vias and / or various other conductive elements formed throughout the PCB substrate 250 connect the electrical contacts 260 to the electrical contacts 267. As previously mentioned, the electrical contacts 260 are wire bonded to bond pads on the top surface of the detector or sensor 280 (e.g., a CMOS die). Visible from the top view 245 of the lid 210 (which in this example is translucent and may be made of glass) are the inlet and outlet fluid ports 205. 1 and 3, in Fig. 4 the flow cell 200 utilizes a single support piece 230 having a notch for accommodating a detector or sensor 280 and electrical contacts 260 such that portions of the support piece 230 are not covered by the lid 210, but rather, in this case, extend in the longitudinal axis beyond the boundaries of the lid 210. The fan-out regions formed from portions of the single support piece 230 are not visible from any of the views in Fig. 4 as they are below the lid 210.

[0120] FIG. 5 illustrates a workflow 500 showing exemplary aspects in the formation of several examples of flow cells, including but not limited to the flow cell 100 shown in FIG. 1 and FIG. 3. Reference numbers utilized in the workflow 500 to refer to various aspects of the flow cell 100 are provided throughout this process flow 500 for illustrative purposes and do not imply any limitations. In FIG. 5, a substrate 150 is fabricated (505) having electrical contacts, such as pogo pads (e.g., FIG. 3, 167) on the bottom and electrical contacts 160 (e.g., wire bond pads) on the top. In some examples, the substrate includes an integrated heater assembly (not shown in FIG. 5). The electrical contacts (e.g., FIG. 3, 167) on the bottom and electrical contacts 160 on the top are connected to each other through the substrate 150 with connectors, including but not limited to vias. As previously described, the substrate 150 may be fabricated from standard PCB laminate materials, including but not limited to FR4 and / or co-fired ceramic sheets. An adhesive and / or film 140 is dispensed and / or applied to the substrate 150 (515) between the electrical contacts 160 on top of the substrate 150. A detector or sensor 180 (e.g., a CMOS die) is oriented (525) on the adhesive and / or film 140 between the electrical contacts 160. The detector or sensor 180 may be oriented using, for example, a pick-and-place machine. At least two support pieces 130 are placed on the adhesive and / or film 140 adjacent the detector or sensor 180 to form a fan-out region (535). In forming the fan-out region, gaps between each portion of the support pieces 130 and the detector or sensor 180 may be filled with, for example, a liquid dispensing adhesive and cured (to create a uniform surface for the fluidic functions of the flow cell 200). The electrical contacts 160 are then wire bonded (545) to electrical contacts (not shown) on the detector or sensor 180 (e.g., a CMOS die). For example, wires 170 may be bonded to electrical contacts 160 (e.g., wire bond pads) (these electrical contacts are not shown) on the substrate 150 and on the detector or sensor 180 (e.g., a CMOS die) to form an electrical connection therebetween. After the wires are utilized to connect the electrical contacts together, the connections may be encased in epoxy.In some instances, this epoxy protection for the electrical connections may be added after the lid 110 is secured to the flow cell 100.

[0121] Returning to FIG. 5, in this process flow 500, another adhesive and / or film 120 is dispensed or applied (555) to a portion of the support piece 130 and a portion around the detector or sensor 180 (e.g., CMOS die). As shown in FIG. 5, the fan-out area formed by the support piece 130 remains adjacent to the detector or sensor 180 (e.g., CMOS die) that is not covered by the adhesive and / or film 120. A lid 110 is attached (565) to this adhesive and / or film 120. The space below the lid 110 and above the active (top) surface of the detector or sensor (e.g., CMOS) 180 and the portion of the support piece 130 (not covered by the film or adhesive 120) forms a flow path. The lid 110 also defines a fluidic flow cell cavity having inlet and outlet fluidic ports 105. The fluidic ports 105 are inlet and outlet openings in the lid 110.

[0122] FIG. 6 is a workflow 600 illustrating a process similar to that of FIG. 5. Referring to FIG. 6, a substrate is fabricated (605) having electrical contacts on a bottom surface and electrical contacts on a top surface (which are connected through the substrate using vias or other such connections). An adhesive and / or film is applied to the substrate (615) between the electrical contacts on the top surface of the substrate. A detector or sensor (e.g., a CMOS die) is oriented (625) on the adhesive and / or film between the electrical contacts. At least two support pieces are placed on the adhesive and / or film adjacent to the detector or sensor to form a fan-out region (635). In forming the fan-out region, gaps between each portion of the support pieces and the detector or sensor may be filled with, for example, a liquid dispensed adhesive and cured. The electrical contacts on the top surface of the substrate are wire bonded (645) to electrical contacts on the active surface (top surface) of the detector or sensor. These wire bond connections may be protected after formation by applying an epoxy. A second adhesive and / or film is applied to a portion of the support piece and a portion of the periphery of the detector or sensor (655). A lid is attached to the adhesive and / or film to define a fluid flow cell cavity having inlet and outlet fluid ports (665). Both the first and second adhesives and / or films are cured at some point after they are applied and utilized to form the attachment.

[0123] FIG. 7 shows a workflow 700 illustrating exemplary aspects in the formation of some examples of flow cells, including but not limited to the flow cell 200 shown in FIG. 2 and FIG. 4. Unlike the flow cell 100 in FIG. 1 and FIG. 3, the flow cell 200 in FIG. 2 and FIG. 4 includes a single support piece 230 for forming a fan-out region. The reference numbers utilized in the workflow 700 refer to various aspects of the flow cell 200 for illustrative purposes and do not introduce any limitations. In FIG. 5, for example, a substrate 250 is fabricated (705) having electrical contacts such as pogo pads (e.g., FIG. 4, 267) on the bottom and electrical contacts 260 (e.g., wire bond pads) on the top. In some examples, the substrate includes a built-in heater assembly (not shown in FIG. 7). The electrical contacts on the bottom (e.g., FIG. 4, 267) and the electrical contacts on the top 260 are connected to each other through the substrate 250 with connectors including but not limited to vias. As previously mentioned, the substrate 250 may be made from standard PCB laminate materials, including but not limited to FR4 and / or co-fired ceramic sheets. The adhesive and / or film 240 is dispensed and / or applied to the substrate 250 (715). The adhesive and / or film 240 extends beyond, but is not formed on, the electrical contacts 260 (so that the electrical contacts 260 can be wirebonded or otherwise connected to electrical contacts of the sensor or detector 280). The detector or sensor 280 (e.g., a CMOS die) is oriented on the adhesive and / or film 240 between the electrical contacts 260 (725). The detector or sensor 280 may be oriented using, for example, a pick and place machine. A single (fan-out) support piece 230 is placed on the adhesive and / or film 240 to form a fan-out region (735). The support piece 230 has a notch 265 (which can be implemented using different methods including but not limited to laser dicing) so that the support piece 230 does not cover the top surface (e.g., active surface) or electrical contacts 260 of the detector or sensor 280. The electrical contacts 260 are then wire bonded (745) to electrical contacts (not shown) on the detector or sensor 280 (e.g., CMOS die).For example, the wires 270 may be bonded to electrical contacts 260 (e.g., wire bond pads) (not shown) on the substrate 250 and on the detector or sensor 280 (e.g., CMOS die) to form an electrical connection therebetween. After the wires and electrical contacts are utilized to connect together, an adhesive (e.g., epoxy) is dispensed into the cavity surrounding the detector or sensor 280 to encapsulate the bond wires and fill the gaps on either side of the detector or sensor 280 (e.g., CMOS die) by capillary action, and another adhesive and / or film 220 is dispensed or applied (755) to a portion of the support piece 230 and the periphery of the detector or sensor 280 (e.g., CMOS die). The lid 210 is attached (765) to the adhesive and / or film 220. The space below the lid 210 and above the active (top) surface of the detector or sensor (e.g., CMOS) 280 and the top surface of the portion of the support piece 230 (not covered by the film or adhesive 120, but covered by the lid 210) forms the flow path. The lid 210 also defines a fluidic flow cell cavity having inlet and outlet fluid ports 205. The fluid ports 205 are inlet and outlet openings in the lid 210.

[0124] FIG. 8 is a workflow 800 illustrating a process similar to that of FIG. 7. Referring to FIG. 8, a substrate is created (805) with electrical contacts on the bottom and electrical contacts on the top (which are connected through the substrate using vias or other such connections). An adhesive and / or film is applied to the substrate (815). A detector or sensor (e.g., a CMOS die) is oriented (825) on the adhesive and / or film between the electrical contacts not covered by the adhesive and / or film. A cutout to accommodate the detector or sensor and a support piece including the electrical contacts are placed on the adhesive and / or film to form a fan-out region (835). The electrical contacts are wire bonded to the electrical contacts on the detector or sensor (845). An adhesive (e.g., epoxy) is dispensed into the cavity surrounding the detector or sensor to encapsulate the bond wires and fill the gaps on either side of the detector or sensor by capillary action (852). Another adhesive and / or film is dispensed or applied to a portion of the support piece and the periphery of the detector or sensor 855. A lid is attached to the adhesive and / or film to define a fluid flow cell cavity having inlet and outlet fluid ports 865. Both the first and second adhesives and / or films are allowed to cure at some point after they are applied and utilized to form the attachment.

[0125] Referring now to FIG. 9, as previously described, some examples of flow cells formed utilizing some aspects of the methods described herein are formed on a substrate that includes various heating elements. FIG. 9 shows a flow cell 100 in a side view 900 similar to the flow cell 100 of FIGS. 1 and 3, with this detail added to the substrate 150. Consistency in numbering is provided for illustrative purposes. The flow cells 200 of FIGS. 2 and 4 share substantially the same elements, potentially saving a single support piece 230 (see FIGS. 2 and 4) that surrounds the detector or sensor 280 on all four sides. FIG. 9 does not duplicate reference numbers for the flow cells of FIGS. 2 and 4, although commonly named elements are relevant to both configurations.

[0126] The flow cell 100 of FIG. 9 includes various aspects that are also visible in other figures. For example, the flow cell 100 includes at least two support pieces 160 on either side of a detector or sensor 180. The support pieces 106 allow for fluid fan-out within the flow cell 100 and may be made of materials including, but not limited to, glass, silicon, and / or ceramic. In this example, the detector or sensor 180 is a CMOS image sensor with a nanowell structure 177 patterned thereon. The support pieces 160 and the detector or sensor 180 are attached to a substrate using an adhesive and / or film 140. This adhesive and / or film 140 may be dispensed or applied as a film and then cured (e.g., thermally cured or UV cured) to create this attachment. The substrate 150 in this example may be made from standard PCB laminate materials including, but not limited to, FR4 and / or co-fired ceramic sheets. The substrate includes electrical connections on its top surface 160 and electrical connections on its bottom surface 167. In this example, the electrical connections on the top surface 160 are (e.g., metal) bond pads, allowing wire bonding to bond pads on the top surface of a detector or sensor 180 (e.g., a CMOS die), while the electrical connections on its bottom surface 167 are pogo pads, allowing electrical connection to a receiving socket or instrument. The flow cell 100 contains a fluid, and a glass lid 110 defines a fluid flow cell cavity having inlet and outlet fluid ports 105. The (e.g., glass) lid 110 is attached to the support piece 160 and a portion of the detector or sensor 180 with an adhesive 120. As with the adhesive and / or film 140, the adhesive or film 120 may also be dispensed or applied as a film. The adhesive or film 120 may then be cured (e.g., thermally or UV cured).

[0127] The substrate 150 of FIG. 9 has an embedded heater to control the temperature of the package. As mentioned above, some or all of these elements may also be integrated into the example flow cell 200 of FIG. 2 and FIG. 4. In the flow cell 100 of FIG. 9, heating may be accomplished by one or more of two methods. First, a power resistor 152 may be placed on the top or bottom of the substrate 150, and the heat is transferred to the desired location by vias 159, and the metal plane 153 spreads the heat over the desired area to maintain a uniform temperature. Second, a long winding metal trace 156 at this desired location may function as a resistive heater without a separate power resistor. The heat spreading metal plane 153 and the long winding metal trace 156 functioning as a resistive heater are shown as being structurally similar. Also, the vias 154 are a metal interconnect layer in the substrate, allowing electrical connection from the detector or sensor 180 to electrical connections on its bottom surface 167.

[0128] Reference is now made to examples including EMC material molded at least in part around a sensor or detector as shown in Figures 10-20. To that end, Figures 10-11 each include assembled and exploded views of flow cells 1000, 1100 having fan-out regions, which are formed, for example, by assembling a package including EMC material molded around a sensor or detector onto a substrate PCB. Figures 12-13 show side views of the package including EMC material and a sensor or detector mounted on flow cells 1000 and 1100, respectively. Figures 14-15 provide top and bottom views of flow cells 1000, 1100, respectively, as shown in Figures 10-11. Figures 10-15 are included to provide an overview of certain elements of the structure of various examples of flow cells 1000, 1100 that may be formed utilizing the methods described herein. Figures 16-19 show these methods in more detail. Specifically, FIG. 16 is a process flow 1600 showing the step-by-step formation of the flow cell 1000 of FIG. 10 (and FIG. 14). FIG. 17 is a workflow 1700 that repeats various aspects of FIG. 16, but without illustration of the flow cell 1000 itself. FIG. 18 is a process flow 1800 showing the step-by-step formation of the flow cell 1100 of FIG. 11 (and FIG. 15). Similar to FIG. 17, FIG. 19 is a workflow 1900 that reviews aspects of the formation of flow cells, including the flow cell 1100 of FIG. 11 (and FIG. 15), without illustration of these aspects. FIG. 20 provides a side view of an example flow cell to show a heating element that may be integrated into the examples discussed herein.

[0129] Referring first to FIG. 10, included in this figure are two views of a flow cell 1000, an assembled view 1025 on the left, and an exploded view 1035 on the right. As shown in this example, a package 1081 containing a detector or sensor (e.g., CMOS) 1080 molded in an EMC material 1082 is attached to a PCB substrate 1050. In some examples, the detector or sensor 1080 is a CMOS image sensor with nanowell structures patterned on it (e.g., on the active surface). The PCB substrate 1050 may be constructed from standard PCB laminate materials, including but not limited to glass-reinforced epoxy laminate materials such as FR4 and / or co-fired ceramic sheets. In some examples, the PCB substrate 1050 includes a built-in heater (not shown). As is more evident in the exploded view 1035, the package 1081 is attached to the PCB substrate 1050 using a film or adhesive. This attachment may or may not be formed by placing the package 1081 on a film or adhesive 1040 using a pick and place tool. In some examples, the adhesive is dispensed and / or a film is applied that attaches the package 1081 to the substrate 1050. This film or adhesive 1040 may be heat cured and / or ultraviolet (UV) cured. Another film or adhesive 1020 is used to attach the lid (e.g., glass) 1010. This film or adhesive 1020 may be dispensed or formed as a film to attach the lid 1010 to the package 1081. The space under the lid 1010 and above the active (top) surface of the detector or sensor (e.g., CMOS) 1080 and the top surface (not covered by the film or adhesive 1020) of the portion of the EMC material 1082 molded around the detector or sensor (e.g., CMOS) 1080 forms a flow path. The lid 1010 defines a fluid flow cell cavity with inlet and outlet fluid ports 1005. Contacts (not shown) on the active surface of a detector or sensor (e.g., CMOS) 1080 are wirebonded 1070 to electrical connections (e.g., bond pads, contact pads) 1060 on the PCB substrate 1050.In some examples, the electrical connections 1060 are metal bond pads on the top surface of the PCB substrate 1050, allowing for wire bonding to bond pads on the top surface of the detector or sensor 1080 (e.g., a CMOS die).

[0130] As seen in FIG. 11, and further illustrated in FIGS. 12-13, the difference between the flow cell 1000 of FIG. 10 and the flow cell 1100 of FIG. 11 is that in FIG. 11, an EMC material 1182 is molded around a sensor or detector (e.g., CMOS) 1180, and a layer 1183 is deposited on the front side of the sensor or detector 1180 and the EMC mold material 1182 to planarize the surface. As discussed in more detail later herein, this layer 1183 is opened (e.g., using lithography or lithography plus lift-off process) onto the sensor or detector and / or active surface. In some examples, the planarizing surface is a photoresist, including but not limited to SU8. In some examples, the layer is patterned and then cured (e.g., baked), as discussed later herein. As shown in this example, a package 1181 including a detector or sensor (e.g., CMOS) 1180 molded in the EMC material 1182 is attached to a PCB substrate 1150. In some examples, such as the example shown in FIG. 10, the detector or sensor 1180 is a CMOS image sensor with nanowell structures patterned on it (e.g., on the active surface). The PCB substrate 1150 may be constructed from standard PCB laminate materials, including but not limited to glass reinforced epoxy laminate materials such as FR4 and / or co-fired ceramic sheets. In some examples, the PCB substrate 1150 includes a built-in heater (not shown). As also shown in the exploded view 1135, the package 1181 is attached to the PCB substrate 1150 using a film or adhesive. This attachment may or may not be formed by placing the package 1181 on the film or adhesive 1140 with a pick and place tool. In some examples, this adhesive is dispensed and / or a film is applied that attaches the package 1181 to the substrate 1150. This film or adhesive 1140 may be heat cured and / or ultraviolet (UV) cured. Another film or adhesive 1120 is used to attach the lid (e.g., glass) 1110. In these examples, the glass lid 1110 is attached to a portion of layer 1183. This film or adhesive 1120 can be dispensed or formed as a film to attach the lid 1110 to the layer 1183.The space beneath the lid 1110 and above the active (top) surface of the detector or sensor (e.g., CMOS) 1180 and the top surface (not covered by film or adhesive 1120) of the portion of the layer 1183 patterned on the EMC material 1182 molded around the detector or sensor (e.g., CMOS) 1180 forms a flow path. The lid 1110 defines a fluidic flow cell cavity having inlet and outlet fluid ports 1105. Contacts (not shown) on the active surface of the detector or sensor (e.g., CMOS) 1180 are wirebonded 1170 to electrical connections (e.g., bond pads, contact pads) 1160 on the PCB substrate 1150. In some examples, the electrical connections 1160 are metal bond pads on the top surface of the PCB substrate 1150, allowing wirebonding to bond pads on the top surface of the detector or sensor 1180 (e.g., CMOS die).

[0131] FIG. 12 is a side view of the flow cell assembly 1000 shown in FIG. 10. A package 1081 containing an EMC material 1082 molded around a sensor or detector 1080 (e.g., CMOS) is attached to a glass lid 1010 using a film or adhesive 1020. The top surface of the EMC material 1072 not covered by the film or adhesive 1020 forms the fan-out region. The space below the lid 1010 and above the active (top) surface of the detector or sensor (e.g., CMOS) 1080 and the top surface (not covered by the film or adhesive 1020) of the EMC material 1072 molded around the detector or sensor (e.g., CMOS) 1080 forms the flow path. The lid 1010 defines a fluidic flow cell cavity with inlet and outlet fluidic ports 1005. The package 1081 includes vias 1087 of a conductive material, such as a metallic material (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum), or combinations thereof), although it is understood that other conductive materials may be utilized. The vias 1087 are embedded in the EMC material 1082 at the bottom side 1086 of the sensor or detector 1080. As previously mentioned, the example flow cell 1000 shown in FIG. 10, among others, may or may not include these vias 1087. Additionally, as shown in FIGS. 21-31, these vias 1087, when embedded in the EMC material 1082, may be embedded in various configurations. The configurations in this example are provided for illustrative purposes only and do not imply any limitations to these configurations.

[0132] FIG. 13 shows a side view of the flow cell 1100 shown in FIG. 11. As mentioned above, the difference between the flow cells 1000, 1100 includes a layer 1183 deposited on the front side of the sensor or detector 1180 and an EMC mold material to planarize the surface in the flow cell 1100. In FIG. 13, the layer 1183 is deposited on a package 1181 including an EMC material 1182 molded around the sensor or detector 1180 (e.g., CMOS). In the example shown herein, the layer 1183 is deposited on the surface of the sensor or detector 1180 and the EMC mold material to planarize the surface. As shown in FIG. 13, this layer 1183 is opened (e.g., using lithography or lithography plus lift-off process) on the sensor or detector and / or active surface to expose the active surface. A portion of the layer 1183, when cured or baked, is attached to the glass lid 1010 using a film or adhesive 1120. The top surface of layer-1183 not covered by film or adhesive 1120 forms the fan-out region. The space below lid 1110 and above the active (top) surface of detector or sensor (e.g., CMOS) 1180 and the top surface of layer-1183 forms the flow path. Lid 1110 defines a fluidic flow cell cavity having inlet and outlet fluidic ports 1105. As in FIG. 12, in the example shown in FIG. 13, the package 1181 includes vias 1187 of a conductive material, such as a metallic material (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum), or a combination thereof), although it is understood that other conductive materials may be utilized. The vias 1187 are embedded in the EMC material 1182 at the bottom side 1186 of the sensor or detector 1180. The example flow cell 1100 shown in FIG. 11, among others, may or may not include these vias 1187. These vias 1187, when embedded in the EMC material 1182, may be embedded in a variety of configurations. The configurations shown in FIG. 13 are provided for illustrative purposes only and do not imply any limitations to these configurations.

[0133] FIG. 14 shows a top view 1045 and a bottom view 1055 of the flow cell 1000. The flow cell 1000 is also shown in FIG. 10, and an embodiment of the flow cell 1000 is shown in FIG. 12. Returning to FIG. 14, the bottom view 1055 of the flow cell 1000, specifically the substrate 1050, shows electrical contacts 1067, which may include pads (called pogo pads) that include pogo pins. These electrical contacts 1067 allow electrical connection of the flow cell 1000 (specifically, ultimately, the detector or sensor 1080) to a receiving socket and / or instrumentation. As shown in later figures, vias and / or various other conductive elements formed throughout the PCB substrate 1050 connect the electrical contacts 1060 to the electrical contacts 1067. As previously mentioned, the electrical contacts 1060 are wire bonded to bond pads on the top surface of the detector or sensor 1080 (e.g., a CMOS die). Visible from a top view 1045 of the lid 1010 (which in this example is translucent and may be made of glass) are the inlet and outlet fluid ports 1005. Beneath the lid 1010, not visible from any of the views in FIG. 14, are fan-out regions, which are formed from portions of the EMC material 1082 in which the detector or sensor 1080 is molded, as shown in FIG. 10. The portions of the EMC material 1082 are not covered by the lid 1010, but rather extend on the longitudinal axis, in this case, beyond the boundaries of the lid 1010. The fan-out regions formed from portions of the EMC material 1082 in which the detector or sensor 1080 is molded, are not visible from any of the views in FIG. 14, as they are beneath the lid 1010.

[0134] Referring to FIG. 15, FIG. 15 shows a top view 1145 and a bottom view 1155 of a flow cell 1100, which is also shown in FIG. 11. The bottom view 1155 of the flow cell 1100, specifically the substrate, shows electrical contacts 1167, which may include pads (called pogo pads) that include pogo pins. These electrical contacts 1167 allow electrical connection of the flow cell 1100 (specifically the detector or sensor 1180) to a receiving socket and / or instrument. As shown in later figures, vias and / or various other conductive elements formed throughout the PCB substrate 1150 connect the electrical contacts 1160 to the electrical contacts 1167. As previously mentioned, the electrical contacts 1160 are wire bonded to bond pads on the top surface of the detector or sensor 1180 (e.g., a CMOS die). Visible from a top view 1145 of the lid 1110 (which in this example is translucent and may be made of glass) are the inlet and outlet fluid ports 1105. Portions of the EMC material 1182 are not covered by the lid 1110, but rather, in this case, extend on the longitudinal axis beyond the boundary of the lid 1110. Portions of layer 1183 patterned on top of the EMC material 1182 also extend on the longitudinal axis beyond the boundary of the lid 1110. Fan-out regions formed from portions of layer 1183 are not visible from any of the views in FIG. 15 because they are under the lid 1110.

[0135] FIG. 16 illustrates a workflow 1600 showing exemplary aspects in the formation of several examples of flow cells, including but not limited to the flow cell 1000 shown in FIG. 10 and FIG. 11. Reference numbers utilized in the workflow 1600 to refer to various aspects of the flow cell 1000 are provided throughout this process flow 1600 for illustrative purposes and do not imply any limitations. In FIG. 16, a substrate 1050 is fabricated (1605) having electrical contacts, such as pogo pads (e.g., FIG. 14, 1067) on the bottom and electrical contacts 1060 (e.g., wire bond pads) on the top. In some examples, the substrate includes an integrated heater assembly (not shown in FIG. 16). The electrical contacts on the bottom (e.g., FIG. 14, 1067) and the electrical contacts on the top 1060 are connected to each other through the substrate 1050 with connectors, including but not limited to vias. As previously described, the substrate 1050 may be fabricated from standard PCB laminate materials, including but not limited to FR4 and / or co-fired ceramic sheets. An adhesive and / or film 1040 is dispensed and / or applied to the substrate 1050 (1615) between the electrical contacts 1060 on top of the substrate 1050. A package 1081 formed from a detector or sensor 1080 (e.g., a CMOS die) molded in an EMC material 1082 is placed on the adhesive with a pick-and-place tool and oriented (1625) on the adhesive and / or film 1040 between the electrical contacts 1060. The detector or sensor 1080 may be oriented using, for example, a pick-and-place machine. The electrical contacts 1060 are then wire bonded (1635) to electrical contacts (not shown) on the detector or sensor 1080 (e.g., a CMOS die). For example, wires 1070 may be bonded to the electrical contacts 1060 (e.g., wire bond pads) (these electrical contacts are not shown) on the substrate 1050 and on the detector or sensor 1080 (e.g., a CMOS die) to form an electrical connection therebetween. After wires are utilized to connect the electrical contacts together, the connections may be encased in epoxy. In some examples, this epoxy protection for the electrical connections may be added after the lid 1010 is secured to the flow cell 1000.

[0136] Returning to FIG. 16, in this process flow 1600, another adhesive and / or film 1020 is dispensed or applied (1645) to a portion of the EMC material 1082 around the periphery of a detector or sensor 1080 (e.g., CMOS die). As shown in FIG. 16, the top surface 1072 of the EMC material 1082 that is not covered by the film or adhesive 1020 and adjacent to the detector or sensor 1080 (e.g., CMOS die) forms a fan-out region. A lid 1010 is attached (1655) to this adhesive and / or film 1020. The space below the lid 1010 and above the active (top) surface of the detector or sensor (e.g., CMOS) 1080 and the top surface 1072 of the EMC material 1082 forms a flow path. The lid 1010 also defines a fluidic flow cell cavity having inlet and outlet fluidic ports 1005. Fluid ports 1005 are inlet and outlet openings in the lid 1010 .

[0137] FIG. 17 is a workflow 1700 illustrating a process similar to that of FIG. 16. Referring to FIG. 17, a substrate is created (1705) with electrical contacts on the bottom surface and electrical contacts on the top surface of the substrate (which are connected through the substrate using vias or other such connections). An adhesive and / or film is applied (1715) to the substrate between the electrical contacts on the top surface of the substrate. A package 1081 formed from a detector or sensor 1080 (e.g., a CMOS die) molded in an EMC material 1082 is oriented (1725) on the adhesive and / or film between the electrical contacts. The electrical contacts on the top surface of the substrate are wire bonded (1735) to electrical contacts on the active surface (top surface) of the detector or sensor. These wire bond connections may be protected after formation by applying an epoxy. A second adhesive and / or film is applied (1745) to a portion of the EMC material around the periphery of the detector or sensor. The lid is attached to an adhesive and / or film to define a fluid flow cell cavity having inlet and outlet fluid ports 1755. Both the first and second adhesives and / or films are allowed to cure at some point after they are applied and utilized to form the attachment.

[0138] FIG. 18 illustrates a workflow 1800 showing an exemplary embodiment in the formation of some examples of flow cells, including but not limited to the flow cell 1100 shown in FIG. 11 and FIG. 13. Unlike the flow cell 1000 of FIG. 10 and FIG. 12, the flow cell 1100 of FIG. 11, FIG. 13, and FIG. 15 includes a layer 1183 deposited on the front side of the sensor or detector 1180 and an EMC mold material 1182 to planarize this surface. In examples including this layer 1183, after the EMC mold material 1182 is molded around the sensor or detector 1180, this layer 1183 is deposited on the front side of the sensor or detector 1180 (e.g., front side CMOS) and the mold material to planarize the surface. The layer 1183 is opened onto the active surface of the sensor or detector 1180 using a process including but not limited to lithography or lithography plus lift-off process. A non-limiting example of such a planarizing surface can be a photoresist such as SU8. After patterning of layer 1183, in some examples, layer 1183 may or may not be hardened by baking.

[0139] The reference numbers utilized in the workflow 1800 refer to various aspects of the flow cell 1100 for illustrative purposes and do not introduce any limitations. In FIG. 18, a substrate 1150 is fabricated (1805) having electrical contacts such as pogo pads (e.g., FIG. 15, 1167) on the bottom and electrical contacts 1160 (e.g., wire bond pads) on the top. In some examples, the substrate includes an integrated heater assembly (not shown in FIG. 18). The electrical contacts on the bottom (e.g., FIG. 15, 1167) and the electrical contacts on the top 1160 are connected to each other through the substrate 1150 with connectors including, but not limited to, vias. As previously mentioned, the substrate 1150 may be fabricated from standard PCB laminate materials including, but not limited to, FR4 and / or co-fired ceramic sheets. An adhesive and / or film 1140 (e.g., FIG. 11 1140) is dispensed and / or applied to the substrate 1150 (1815). The adhesive and / or film 1140 extends beyond the electrical contacts 1160 but is not formed on the electrical contacts 1160 (so that the electrical contacts 1160 can be wirebonded or otherwise connected to electrical contacts of the sensor or detector 1180). A package 1181 containing the sensor or detector 1180 molded in the EMC material 1182 is planarized on top with a patternable resist, including but not limited to SU8 (forming layer 1183), and oriented (1825) on the adhesive and / or film 1140, between the electrical contacts 1160. The planarized package 1181 (forming layer 1183) may be oriented, for example, using a pick and place machine. The electrical contacts 1160 are then wirebonded (1835) to electrical contacts (not shown) on the detector or sensor 1180 (e.g., a CMOS die). For example, wires 1170 may be bonded to electrical contacts 1160 (e.g., wire bond pads) (not shown) on the substrate 1150 and on the detector or sensor 1180 (e.g., CMOS die) to form an electrical connection therebetween. After utilizing wires 1170 to connect the electrical contacts together, an adhesive (e.g., epoxy) 1120 is dispensed (1845) (e.g., in a film) onto a portion of the layer around the periphery of the sensor or detector 1180.A lid 1110 is attached (1865) to this adhesive and / or film 1120. The space below the lid 1110 and above the active (top) surface of the detector or sensor (e.g., CMOS) 1180 and the top surface of portions of layer 1183 (not covered by film or adhesive 1120, but covered by the lid 1110) forms the flow path. The lid 1110 also defines a fluidic flow cell cavity having inlet and outlet fluid ports 1105. The fluid ports 1105 are inlet and outlet openings in the lid 1110. The adhesive and / or film 1120 is cured.

[0140] FIG. 19 is a workflow 1900 illustrating a process similar to that of FIG. 18. Referring to FIG. 19, a package including a sensor or detector is formed by molding an EMC material around the sensor or detector (1902). A layer (e.g., photoresist) is deposited on the front side of the package (including the sensor or detector (e.g., front CMOS) and mold material) to planarize the surface (1903). The layer is opened over the sensor or detector to expose the active surface (1904). The layer may or may not be opened using a process including, but not limited to, lithography or lithography plus lift-off processes. A non-limiting example of such a planarizing surface may be a photoresist such as SU8. After patterning the layer, in some examples, the layer may or may not be hardened by baking. A substrate is created (1905) with electrical contacts on the bottom surface and electrical contacts on the top surface (which are connected through the substrate using vias or other such connections). An adhesive and / or film is applied to the substrate (1915). A package containing a detector or sensor (e.g., a CMOS die) molded into the EMC material is oriented (1925) over the adhesive and / or film, with the package planarized with a layer of patternable resist and between electrical contacts not covered by the adhesive and / or film. The electrical contacts are wire bonded (1935) to electrical contacts on the detector or sensor. In some examples, an adhesive (e.g., epoxy) is dispensed into the cavity surrounding the detector or sensor to encapsulate the bond wires. Another adhesive and / or film is dispensed or applied (1945) to a portion of the layer around the periphery of the detector or sensor. A lid is attached to the adhesive and / or film, defining a fluid flow cell cavity having inlet and outlet fluid ports (1955). Both the first and second adhesives and / or films are cured at some point after they are applied and utilized to form the attachment.

[0141] Referring now to FIG. 20, as previously described, some examples of flow cells formed utilizing some aspects of the methods described herein are formed on a substrate that includes various heating elements. Similar to FIG. 9, FIG. 20 shows a flow cell 1000 in a side view 2000 similar to the flow cell 1000 of FIGS. 10 and 12, with this detail added to the substrate 1050. Consistency in numbering is provided for illustrative purposes. The flow cells 1100 of FIGS. 11 and 13 may share substantially the same elements, including a patterned layer (e.g., FIG. 13 1183) over the EMC material (e.g., FIG. 13, 1182). FIG. 20 does not duplicate reference numbers for the flow cells of FIGS. 11 and 13, although commonly named elements relate to both configurations.

[0142] 12 and 13, in FIG. 20, an EMC material 1082 is molded around a sensor or detector 1080 (e.g., a CMOS die) that has embedded vias 1087 of a conductive material, such as a metallic material (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum), or combinations thereof). Examples of the structure and formation of the EMC material 1082 embedded in the vias 1087 are further discussed with reference to FIGS. 21-32.

[0143] Returning to FIG. 20, the flow cell 1000 of FIG. 20 includes various additional aspects that are also visible in other figures. For example, the flow cell 1000 includes a package 1081 that includes an EMC material 1082 molded around a sensor or detector 1080 to provide fluid fan-out for utilization across the active surface of the flow cell 1000. In this example, the detector or sensor 1080 is a CMOS image sensor with a nanowell structure 1077 patterned thereon. The package 1081 is attached to a substrate with an adhesive and / or film 1040. This adhesive and / or film 1040 may be dispensed or applied as a film and then cured (e.g., thermally or UV cured) or uncured to create this attachment. The substrate 1050 in this example may be made from standard PCB laminate materials, including but not limited to FR4 and / or co-fired ceramic sheets. The substrate includes electrical connections on its top surface 1060 and electrical connections on its bottom surface 1067. In this example, the electrical connections on the top surface 1060 are (e.g., metal) bond pads, allowing for wire bonding to bond pads on the top surface of a detector or sensor 1080 (e.g., a CMOS die), while the electrical connections on its bottom surface 1067 are pogo pads, allowing for electrical connection to a receiving socket or instrument. The flow cell 1000 contains a fluid, and a glass lid 1010 defines a fluid flow cell cavity having inlet and outlet fluid ports 1005. The (e.g., glass) lid 1010 is attached to a support piece 1060 and a portion of the detector or sensor 1080 with an adhesive 1020. As with the adhesive and / or film 1040, this adhesive or film 1020 may also be dispensed or applied as a film and then cured (e.g., thermally or UV cured) or uncured.

[0144] The substrate 1050 of FIG. 20 has an embedded heater to control the temperature of the package. As mentioned above, some or all of these elements may also be integrated into the example flow cell 1100 of FIG. 11 and FIG. 13. In the flow cell 1000 of FIG. 20, heating may be accomplished by one or more of two methods. First, a power resistor 1052 may be placed on the top or bottom of the substrate 1050, and the heat is transferred to the desired location by vias 1059, and the metal plane 1053 spreads the heat over the desired area to maintain a uniform temperature. Second, a long winding metal trace 1056 at this desired location may function as a resistive heater without a separate power resistor. Structurally similar are shown the heat spreading metal plane 1053 and the long winding metal trace 1056 functioning as a resistive heater. Also, the vias 1054 are a metal interconnect layer in the substrate, allowing electrical connection from the detector or sensor 1080 to electrical connections on its bottom surface 1067.

[0145] In the example flow cells 1000, 1100 of FIGS. 10 and 11, the flow cells 1000, 1100 include a package 1081, 1181 which itself includes an EMC material 1082, 1182 molded around a sensor or detector 1080, 1180.

[0146] 21-32 show various examples of methods of forming a package including a hardened molding material (e.g., EMC material) surrounding portions of one or more dies, as well as one or more pillars or vias of conductive material (e.g., 2181, FIG. 29), as previously described. For consistency, as much as possible, the same designers are used for common and / or similar elements in these figures, as in the previous figures. In the formed packages, the dies (e.g., sensors or detectors) are at least partially embedded in the molding material, as are the pillars. These packages thus include aspects of the packages 1081 and 1181 of the flow cells 1000 and 1100. As previously described, in some example flow cells discussed herein, the packages 1081 and 1181 may be substantially the same or somewhat similar to the packages shown in FIGS. 21A-21K. However, unlike previous figures that have focused or shown the formation of flow cells, which may or may not include this type of package in particular, FIGS. 21-32 focus on example details regarding forming the package itself. While Figures 21-31 show examples of various elements in the overall formation of a flow cell through packaging and an example of a completed flow cell, Figure 33 reviews, for clarity, some of the elements of the example shown in Figures 21-31, but is not illustrated.

[0147] Referring first to FIGS. 21-23, in these non-limiting examples, a package is formed on a carrier (e.g., a glass carrier) by attaching elements such as pillars 2114 and a die (e.g., a sensor or detector) 2113 to the carrier 2111 (e.g., ceramic or glass) using a temporary adhesive 2112. Shown in FIG. 21 is the carrier 2111 and the temporary adhesive 2112 (e.g., a film or adhesive) dispensed onto the carrier 2111. The adhesive 2112 is temporary as its removal (including removal of the carrier 2111) is also part of this example and will be described below. For example, the surface of the die 2113 becomes the active surface of the sensor or detector 2180 and is attached to the temporary adhesive 2112. The surfaces of the sensor or detector 2180 are labeled in FIGS. 23-31 but may or may not be effective as a sensor or detector 2180 until subjected to chemical treatment as discussed and illustrated in FIG. However, with specific reference to Figures 22-23, one or more pillars 2114 and one or more dies 2113 are oriented on a temporary adhesive 2112 on a carrier 2111. In some examples, these elements may be oriented utilizing a pick-and-place procedure.

[0148] In the example shown in Figures 21-31, the orientation of the vias (e.g., pillars 2114) and die 2113 is such that each of the die 2113 is between two pillars 2114. This orientation is provided by way of example only. The pillars 2113 provide electrical connections from each of the sensors or detectors 2180 to any elements below the package, including the substrate. While this particular orientation illustrates this advantage, one skilled in the art will appreciate that a variety of different orientations can be utilized to provide similar or the same functionality. As previously described in Figures 12 and 13, the vias 1087, 1187 can be oriented below the sensors or detectors 1080, 1180. Because the vias 1087, 1187 in Figures 21-31 illustrate a particular configuration of conductive elements that differs from some of the previously discussed orientations, these conductive elements are referred to as pillars 2114 for clarity.

[0149] 24, a material (e.g., EMC material 2182) is molded onto the carrier 2111 such that the pillars 2114 and die 2113 are embedded in the EMC material 2182. As seen in FIG. 24, the EMC material 2182 may or may not cover all surfaces of the pillars 2114 and die 2113 except for those surfaces that are affixed to the temporary adhesive 2112. The EMC material 2182 is hardened, which may or may not be achieved by baking the material. In some examples, including the one shown in FIG. 24, the top surface formed by the mold exceeds the height of the pillars 2114, which is higher than the die 2113.

[0150] 25, as previously mentioned, a particular advantage of the EMC material packages discussed herein is that they include vias (e.g., pillars 2114) that provide electrical connectivity to the sensors or detectors 1080, 1180, 2180 throughout the package, thereby making the pillars accessible by grinding the EMC material and forming a surface 2116 that includes the die 2113 and the pillars 2114. In some examples, these pillars 2114 are copper, which aids in the grinding process.

[0151] FIG. 26 shows that the top surface of the pillars 2114 is plated with a conductive material (e.g., nickel or gold) to create a seed layer 2117. As discussed herein, in some examples, this seed layer is used to connect the pillars 2114 to additional vias 2118 (e.g., FIG. 27). In some examples, a seed layer is not utilized and a redistribution layer (RDL) pad or some other electrical contact serves as a mechanism to enable electrical coupling to the pillars 2114 and ultimately the sensor or detector 2180. FIGS. 27-31 do not depict the seed layer 2117 because it is not implemented or, if implemented, is not visible.

[0152] In FIG. 27, one or more redistribution layers (RDLs) 2121 are applied to the surface 2116. Each applied RDL may or may not be patterned on the surface 2116. In some examples, after each RDL (of the RDLs 2121) is patterned, a portion of the RDL is opened to provide accessibility to the electrical elements. One non-limiting example of a process that may be utilized to form the openings 2122 is photolithography. A conductive material 2118 (e.g., copper) extends through the openings 2122 such that the material is electrically coupled to one or more of the pillars 2114. The material in the openings 2122 forms vias to the pillars 2114. Various non-limiting examples include one to three RDLs. The openings 2122 in the top RDL are plated (e.g., with gold and / or copper) to form electrical contacts 2119.

[0153] 28-29, once the electrical contacts 2119 are formed, as shown in FIG. 28, the structure (so far) may be rotated 180 degrees, the temporary adhesive 2112 disengaged, and both the temporary adhesive 2112 and the carrier 2111 removed from the structure. FIG. 28 shows the structure rotated and the temporary adhesive 2112 and carrier 2111 removed. Removing the temporary adhesive 2112 and carrier 2111 exposes the surface of the package including what will become the active surface 2123 (see FIG. 29). FIG. 29 shows an example of at least one package 2181. As shown in FIG. 29, a chemical 2124 is applied to the surface of each die 2113 to enable the treated surface of the die to act as a detector or sensor 2180 in a particular flow cell. This treated portion of the surface is at least a portion of the active surface 2123 in some flow cells.

[0154] As discussed herein, the pillars 2114 provide connectivity through the package to the sensor or detector 2180, and thus FIG. 30 shows two different non-limiting examples of the type of connection that can be made between the electrical contacts 2119 and the sensor or detector 2180. On the left side of FIG. 20, the electrical contacts 2126 are wirebonded to the sensor or detector 2180. On the right side, printing is utilized to make printed connections 2127 between the sensor or detector 2180 and the electrical contacts 2119. In FIG. 31, a lid 2110 is added over each active surface 2123, defining fluid flow paths 2128 above the active surface 2123 and below the lid 2110. In some examples, an adhesive is used to secure the lid 2110 to the top surface of the package 2181.

[0155] FIG. 32 is a workflow 3200 reviewing aspects of the formation of the flow cell 2100. The workflow 3200 illustrates an aspect of assembling a package including a hardened molding material surrounding a portion of one or more dies. In this example, one or more pillars of conductive material (e.g., copper, gold, etc.) are embedded in the molding material. To assemble the package, an adhesive is applied to a surface of the carrier (e.g., glass, ceramic, etc.) (3205). The one or more pillars and one or more dies are oriented (e.g., using pick and place) on the adhesive (3215). In some examples, the pillars are of a greater vertical length than the dies. A material (e.g., EMC material) is molded around the top surface of the carrier and the surface of the one or more dies and portions of the one or more pillars such that the top surface of the mold is of a greater vertical length than the pillars, and the mold is cured (3225). The surface of the hardened molding material is ground to expose the top surfaces of the one or more pillars and the top surfaces of the one or more dies to create a new surface (3235). The top surfaces of the pillars are plated with a conductive material to create a seed layer of conductive vias (3245). To form these vias, one or more redistribution layers are applied, including patterning each layer onto a new surface, opening portions of the layer to form openings, and spreading the conductive material into each opening so that the conductive material spreads through the openings, forming vias in one or more pillars (3255). Electrical contacts are attached to the vias, and the carrier and temporary adhesive are removed to expose the package surface (3265). Now that the package is formed, in some instances, a chemical is applied to the package surface at the exposed die surfaces, and the exposed pillar surfaces are plated to form electrical contacts (3275). The electrical contacts are electrically coupled to portions of the surface of the one or more die that have been or will be treated with the chemicals (3297). A lid is attached to the package in an orientation that defines fluidic channels over the surface of the die where the chemicals have been or will be applied (3299).

[0156] Examples described herein include methods for forming a flow cell, as well as the flow cell itself. The method may include applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts. The method may include orienting a package on the first adhesive, the package including a die, the top surface of the die including an active surface and electrical contacts, and a surface adjacent to the active surface on at least two opposite sides of the active surface forming a fan-out region for use in a fluidic path of the flow cell. The method may include connecting electrical contacts on the top surface of the substrate to the electrical contacts on the die. The method may include applying a second adhesive to a portion of the package and attaching a lid to the second adhesive. The attaching defines a fluidic flow cell cavity under the lid and above the surface including the active surface and the fan-out region.

[0157] In some examples, the method may include forming a package, where forming the package includes orienting the die on the first adhesive. The method may also include forming a fan-out region by orienting one or more support pieces on the first adhesive adjacent at least two sides of the die, where the fan-out region includes a portion of a top surface of the support pieces.

[0158] In some examples, the one or more support pieces include two support pieces, and orienting the one or more support pieces on the first adhesive adjacent to at least two sides of the die includes positioning the two support pieces adjacent to the die on either side of the die.

[0159] In some examples, the one or more support pieces include a single support piece, the single support piece including a notch, and orienting the one or more support pieces on the first adhesive adjacent to at least two sides of the die includes orienting the single support piece such that the die and the electrical contacts are within the notch.

[0160] In some examples, the package includes a cured electronic molding compound (EMC) material molded around a portion of the die, where a portion of the EMC material includes the fan-out region.

[0161] In some examples of the methods disclosed herein, forming the fan-out region further includes dispensing material to fill a gap between the one or more support pieces and the die.

[0162] In some examples of methods of forming a flow cell, the one or more support pieces comprise a material selected from the group consisting of glass, silicon, and ceramic.

[0163] In some examples of methods of forming a flow cell, the package includes a cured electronic molding compound (EMC) material molded around a portion of the die and a layer deposited on a surface of the EMC material adjacent the active surface on at least two opposite sides of the active surface, and the fan-out region includes a portion of the layer.

[0164] In some examples of methods of forming a flow cell, the method includes forming a package that includes curing the EMC material around a portion of the die.

[0165] In some examples of the method of forming a flow cell, forming the package further includes planarizing a surface of the EMC material adjacent the active surface.

[0166] In some example methods of forming a flow cell, planarizing includes depositing a layer on a surface including the top surface of the die and an EMC material surface adjacent the active surface, opening the layer on the active surface, and curing the layer.

[0167] In some examples of methods for forming a flow cell, the layer comprises a photoresist.

[0168] In some examples of methods of forming a flow cell, the technique for opening the layers is selected from the group consisting of lithography and lithography plus lift-off.

[0169] In some examples of the method of forming the flow cell, forming the package further includes embedding vias in the EMC material before curing the EMC material around the portion of the die.

[0170] In some examples of methods of forming a flow cell, the vias are constructed from a conductive material.

[0171] In some examples of methods for forming a flow cell, the conductive material is selected from the group consisting of copper, gold, tungsten, and aluminum.

[0172] In some example methods of forming a flow cell, vias extend through the EMC material from a surface of the die opposite the active surface in a direction opposite the active surface.

[0173] In some example methods of forming a flow cell, connecting electrical contacts on the top surface of the substrate to electrical contact points on the die includes wire bonding the electrical contacts to the electrical contact points.

[0174] In some examples of methods of forming a flow cell, the method includes encapsulating wire bonded connections with epoxy.

[0175] In some examples of the methods of forming a flow cell, the methods include curing the first adhesive and the second adhesive.

[0176] In some examples of methods of forming a flow cell, the curing is selected from the group consisting of thermal curing and ultraviolet (UV) curing.

[0177] In some examples of methods for forming a flow cell, the substrate is a printed circuit board.

[0178] In some examples of methods for forming a flow cell, the substrate comprises a material selected from the group consisting of glass reinforced epoxy laminate material, FR4, and co-fired ceramic sheets.

[0179] In some examples of the methods of forming a flow cell, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0180] In some examples of methods of forming a flow cell, the methods include forming a heating element in a substrate.

[0181] In some example methods of forming a flow cell, forming the heating element includes disposing one or more resistors on one or more of a top surface of the substrate and a bottom surface of the substrate, and coupling the one or more resistors to a metal plane in the substrate through a via.

[0182] Some example methods of forming a flow cell include forming a heating element in a substrate such that the heating element includes a long wound metal trace and acts as a resistive heater.

[0183] In some examples of the methods of forming a flow cell, applying the second adhesive further includes applying the second adhesive to a portion of the die.

[0184] In some examples of methods of forming a flow cell, the die is a complementary metal oxide semiconductor.

[0185] In some examples of methods of forming a flow cell, the lid includes two openings, each opening defining one of the inlet or outlet fluid ports.

[0186] In some examples of methods of forming a flow cell, the active surface of the die includes a nanowell.

[0187] In some examples of flow cells disclosed herein, the flow cell may include a substrate including electrical contacts on a top surface. The electrical contacts on the top surface of the substrate are connected to electrical contact points on the top surface of the die. The flow cell may also include a first curing adhesive, the first curing adhesive being bonded to the package. The package may include a die, the top surface of the die further including an active surface, and a fan-out region including a surface adjacent at least two opposite sides of the active surface, the fan-out region at least partially defining a fluidic path of the flow cell. The flow cell may also include a second curing adhesive, the second curing adhesive bonding a portion of the top surface of the package to a lid to define a fluidic flow cell cavity below the lid and above the surface including the active surface and the fan-out region. The flow cell may also include a lid.

[0188] In some examples of the flow cell, the package further includes one or more support pieces adjacent at least two opposing sides of the active surface of the die, the one or more support pieces including a fan-out region.

[0189] In some examples of the flow cell, the one or more support pieces include two support pieces oriented on at least two opposite sides of the active surface of the die.

[0190] In some examples of the flow cell, the one or more support pieces include a support piece, the support piece including a notch, and the die and electrical contacts on the top surface of the substrate are oriented within the notch.

[0191] In some examples of the flow cell, the package further includes a cured electronic molding compound (EMC) material molded around a portion of the die and a portion of the EMC material forming an EMC material surface adjacent the active surface on at least two opposing sides of the active surface, the portion of the EMC material surface including a fan-out region.

[0192] In some examples of the flow cell, the package includes a cured electronic molding compound (EMC) material molded around a portion of the die, and a layer deposited on a surface of the EMC material adjacent the active surface on at least two opposite sides of the active surface, the fan-out region including a portion of the layer.

[0193] In some examples of the flow cell, the package further includes vias embedded in the EMC material.

[0194] In some examples of the flow cell, the one or more support pieces comprise a material selected from the group consisting of glass, silicon, and ceramic.

[0195] In some examples of the flow cell, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0196] In some examples of the flow cell, the substrate further includes a heating element.

[0197] In some examples of the flow cell, the heating element includes one or more resistors on one or more of the top surface of the substrate and the bottom surface of the substrate, a metal plane in the substrate, and a via through the substrate coupling the one or more resistors in the substrate to the metal plane.

[0198] In some examples of flow cells, the heating element comprises a long wound metal trace within a substrate to function as a resistive heater.

[0199] In some examples of the flow cell, the lid includes two openings, each opening defining one of the inlet or outlet fluid ports.

[0200] In some examples of the flow cell, the top surface of the die contains nanowells.

[0201] In some examples of flow cells, the substrate is a printed circuit board.

[0202] In some examples of the flow cell, the substrate comprises a material selected from the group consisting of a glass reinforced epoxy laminate material, FR4, and a co-fired ceramic sheet.

[0203] In some examples of the flow cell, the die is a complementary metal oxide semiconductor.

[0204] In some examples of the methods disclosed herein, the method may include applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts. The method may also include orienting a die onto the first adhesive, the top surface of the die including the active surface and the electrical contacts. The method may also include forming a fan-out region for use in a fluidic path of a flow cell, the forming the fan-out region including orienting one or more support pieces onto the first adhesive adjacent at least two sides of the die, the forming a portion of a top surface of the support piece on at least two sides of the die including the fan-out region. The method may further include connecting electrical contacts on the top surface of the substrate to the electrical contacts on the die. The method may include applying a second adhesive to a portion of the one or more support pieces. The method may also include attaching a lid to the second adhesive, the attaching defining a fluidic flow cell cavity beneath the lid and above a surface including the active surface and the fan-out region.

[0205] In some examples of the methods disclosed herein, the one or more support pieces include two support pieces, and orienting the one or more support pieces on the first adhesive adjacent at least two sides of the die includes positioning the two support pieces adjacent both sides of the die.

[0206] In some examples of the methods disclosed herein, the one or more support pieces include a single support piece, the single support piece including a notch, and orienting the one or more support pieces on the first adhesive adjacent to at least two sides of the die includes orienting the single support piece such that the die and the electrical contacts are within the notch.

[0207] In some examples of the methods disclosed herein, the methods also include securing the wire bonded connections with epoxy.

[0208] In some examples of the methods disclosed herein, forming the heating element includes mounting long winding metal traces within the substrate to act as resistive heaters.

[0209] In some examples of the methods disclosed herein, the methods also include heating the substrate utilizing a heating element.

[0210] Some examples of flow cells disclosed herein include a substrate including electrical contacts on a top surface thereof, the electrical contacts on the top surface of the substrate being connected to electrical contact points on the top surface of the die; a first cured adhesive, the first cured adhesive bonding the die and one or more support pieces adjacent at least two sides of the die to the substrate, with a portion of the top surface of the die and a portion of the top surface of the one or more support pieces forming a surface utilized in the fluid path of the flow cell; a second cured adhesive, the second cured adhesive bonding an area of ​​the one or more support pieces and an area of ​​the top surface of the die adjacent the surface utilized in the fluid path of the flow cell to a lid; and a lid, the lid defining a fluidic flow cell cavity above the surface utilized in the fluid path of the flow cell and below the lid.

[0211] In some examples of flow cells disclosed herein, the one or more support pieces include two support pieces oriented on opposite sides of the die.

[0212] In some examples of the flow cells disclosed herein, the lid includes two openings, each opening defining one of the inlet or outlet fluid ports.

[0213] In some examples of the methods disclosed herein, the method of forming a flow cell includes applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts. The method may also include orienting a die onto the first adhesive, the top surface of the die including an active surface and electrical contact points. The method may also include forming a fan-out region for use in a fluid path of the flow cell, the forming the fan-out region including orienting two support pieces on the first adhesive on either side of the die, each of the two support pieces being adjacent to the die, the top surface of the die and the top surfaces of the two support pieces forming a top surface, and dispensing a material to fill a gap between the two support pieces and the die. The method may also include connecting the electrical contacts on the top surface of the substrate to the electrical contact points on the die. The method may also include applying a second adhesive to a portion of one or more support pieces and a portion of the die. The method may also include attaching the lid to a second adhesive, the attaching defining a fluid flow cell cavity below the lid and above the top surface.

[0214] In some examples of the methods disclosed herein, the method of forming a flow cell includes applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts. The method may also include orienting a die onto the first adhesive, the top surface of the die including an active surface and electrical contacts. The method may also include forming a fan-out region for use in a fluid path of the flow cell, the forming the fan-out region including orienting a support piece onto the first adhesive, the support piece including a notch, and the orienting includes placing the support piece onto the first adhesive such that the die and electrical contacts are positioned within the notch, the fan-out region including a portion of the top surface of the support piece on either side of the die, the portion of the top surface and the active surface forming a top surface. The method also includes connecting the electrical contacts on the top surface of the substrate to the electrical contacts on the die with bond wires. The method also includes dispensing a second adhesive into the notch such that the second adhesive fills a space within the notch between the die and the support piece and encapsulates the bond wire. The method also includes applying a third adhesive to a portion of the support piece and a portion of the die. The method also includes attaching a lid to the third adhesive, the attaching defining a fluid flow cell cavity below the lid and above the top surface.

[0215] In some examples of the methods disclosed herein, a method of forming a flow cell includes applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts. The method may also include orienting a package including a cured electronic molding compound (EMC) material molded around a portion of a die, the top surface of the die including an active surface and electrical contacts, and a portion of the EMC material forming an EMC material surface adjacent to the active surface on at least two opposite sides of the active surface. The method may also include connecting the electrical contacts on the top surface of the substrate to the electrical contacts on the die. The method may also include applying a second adhesive to a portion of the top surface of the package and attaching a lid to the second adhesive, the attaching defining a fluidic flow cell cavity below the lid and above a surface including the active surface and a fan-out region for utilization in a fluid path of the flow cell, the fan-out region including another portion of the top surface of the package.

[0216] In some examples of the methods disclosed herein, the fan-out region is comprised of an EMC material surface adjacent to the active surface on at least two opposing sides of the active surface.

[0217] In some examples of the methods disclosed herein, the package further includes a layer deposited on the EMC material surface adjacent the active surface on at least two opposite sides of the active surface, and the fan-out region includes a portion of the layer deposited on the EMC material surface adjacent the active surface on at least two opposite sides of the active surface.

[0218] In some examples of the methods disclosed herein, connecting the electrical contacts on the top surface of the substrate to the electrical contact points on the die includes wire bonding the electrical contacts to the electrical contact points.

[0219] In some examples of the methods disclosed herein, the method includes securing the wire bonded connections with epoxy.

[0220] In some examples of the methods disclosed herein, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0221] In some examples of the methods disclosed herein, the package further includes a via embedded in the EMC material.

[0222] Some examples of flow cells disclosed herein include a substrate including electrical contacts on a top surface thereof, the electrical contacts on the top surface of the substrate being connected to electrical contact points on a top surface of the die. The flow cell may also include a first curing adhesive that bonds a package including a cured electronic molding compound (EMC) material molded around a portion of the die, the top surface of the die being exposed and including an active surface and electrical contact points, a portion of the EMC material forming an EMC material surface adjacent the active surface on at least two opposite sides of the active surface, the portion of the EMC material surface including a fan-out region for use in a fluidic path. The flow cell may also include a second curing adhesive that bonds a portion of the top surface of the package to a lid to define a fluidic flow cell cavity below the lid and above the surface including the active surface and the fan-out region. The flow cell may also include a lid.

[0223] In some examples of the flow cells disclosed herein, the top surface of the die contains nanowells.

[0224] In some examples of the flow cells disclosed herein, the substrate is a printed circuit board and the die is a complementary metal oxide semiconductor.

[0225] In some examples of the flow cells disclosed herein, the substrate further includes electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0226] Some examples of flow cells disclosed herein include a substrate including electrical contacts on a top surface thereof, the electrical contacts on the top surface of the substrate being connected to electrical contact points on a top surface of a die. The flow cell may include a first curing adhesive that bonds a package including a cured electronic molding compound (EMC) material molded around a portion of the die, the top surface of the die being exposed and including an active surface and electrical contact points, a portion of the EMC material forming an EMC material surface adjacent to the active surface on at least two opposite sides of the active surface, a layer planarizing the EMC material surface, the portion of the EMC material surface planarized by the layer including a fan-out region for use in a fluid path. The flow cell may include a second curing adhesive that bonds a portion of the top surface of the package to a lid to define a fluid flow cell cavity below the lid and above the surface including the active surface and the fan-out region. The flow cell may include a lid.

[0227] In some examples of methods for forming elements usable in one or more flow cells described herein, the method includes assembling a package including a hardened molding material surrounding a portion of one or more dies, where one or more pillars of a first conductive material are embedded in the molding material, and assembling includes applying a temporary adhesive to a surface of the carrier. The method may also include orienting the one or more pillars on the adhesive. The method may also include orienting the one or more dies on the adhesive such that the one or more pillars are oriented between each of the one or more dies, where each of the one or more pillars is of a greater vertical length than each of the one or more dies. The method may also include molding a material around a top surface of the carrier and a surface of the one or more dies and a portion of the one or more pillars, where the top surface of the mold is of a greater vertical length than the one or more pillars, where the top surface of the mold is parallel to the surface of the carrier. The method may also include hardening the molding material. The method may also include grinding a top surface of the mold to expose a top surface of the one or more pillars and a top surface of the one or more dies to create a new surface. The method may also include plating a top surface of the one or more pillars with a second conductive material to create a seed layer. The method may also include applying one or more redistribution layers (RDLs), where applying each RDL includes patterning the layer over a new surface. The method may also include opening a portion of the layer to form an opening. The method may also include spreading a third conductive material into each opening such that the third conductive material spreads through the opening and is electrically coupled to the seed layer. The method may also include attaching an electrical contact to a portion of the third conductive material within the opening of the RDL of the one or more RDLs. The method may also include removing the carrier and the temporary adhesive to expose the package surface.

[0228] In some examples of the methods disclosed herein, the method includes applying a surface chemistry to surfaces of the one or more die exposed by removing the carrier and the temporary adhesive, and plating surfaces of the one or more pillars exposed by removing the carrier and the temporary adhesive to create electrical contacts on the pillars.

[0229] In some examples of the methods disclosed herein, the method includes electrically coupling electrical contacts on the pillars to portions of a surface of the one or more die that include the chemical.

[0230] In some examples of the methods disclosed herein, the method of electrically coupling the electrical contacts on the pillars to the portion of the surface of the one or more dies that contains the chemicals is selected from the group consisting of wirebonding and printing.

[0231] In some examples of the methods disclosed herein, the method includes attaching one or more lids to a package surface, wherein a fluid flow cell cavity is defined beneath each of the one or more lids and above a surface of each of the corresponding one or more sensors that includes an active surface.

[0232] In some examples of the methods disclosed herein, the first conductive material and the third conductive material are copper.

[0233] In some examples of the methods disclosed herein, the second conductive material includes one or more of nickel and gold.

[0234] In some examples of the methods disclosed herein, attaching the one or more lids includes applying an adhesive to a portion of the package surface.

[0235] In some examples of the methods disclosed herein, opening portions of the layer to form openings includes utilizing photolithography.

[0236] In some examples of the methods disclosed herein, the one or more RDLs comprises three RDLs.

[0237] In some examples of the methods disclosed herein, orienting the one or more pillars and orienting the one or more die includes utilizing a pick-and-place tool.

[0238] In some examples of the methods disclosed herein, the molding material includes an electronic molding compound (EMC) material.

[0239] In some examples of flow cells disclosed herein, the flow cell includes a package including a hardened material molded around a portion of a die, where one or more pillars of a first conductive material are embedded in the molded material, and where a top surface of the package includes an active surface of the die. The flow cell may also include a lid attached to a portion of the top surface of the package, where a fluidic flow cell cavity is defined below the lid and above the active surface.

[0240] In some examples of flow cells disclosed herein, the package includes one or more redistribution layers (RDLs) attached to a bottom surface of the package, the RDLs including openings filled with a conductive material electrically coupled to at least one of the one or more pillars.

[0241] In some examples of the flow cells disclosed herein, the package includes electrical contacts that are electrically coupled to the conductive material in the openings of the one or more RDLs.

[0242] In some examples of the flow cells disclosed herein, the curable material includes an electronic molding compound (EMC).

[0243] The flowcharts and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various examples of the present implementations. In this regard, each block in the flowcharts or block diagrams represents a module, segment, or portion of instructions, which includes one or more executable instructions for implementing a specified logical function. In some alternative implementations, the functions shown in the blocks may occur in an order different from the order shown in the figures. For example, two blocks shown in succession may in fact be executed substantially simultaneously, or the blocks may sometimes be executed in reverse order depending on the functionality involved. It should also be noted that each block of the block diagrams and / or flowchart diagrams, and combinations of blocks in the block diagrams and / or flowchart diagrams, may be implemented by a dedicated hardware-based system that performs a particular function or operation, or may be executed by a combination of dedicated hardware and computer instructions.

[0244] The terms used herein are for the purpose of describing particular 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 unless the context clearly dictates otherwise. It will be further understood that the terms "comprises" and / or "comprising," as used herein, specify the presence of stated features, integers, steps, processes, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, processes, operations, elements, components, and / or groups thereof.

[0245] Where applicable, the corresponding structures, materials, acts, and equivalents of all means or steps in addition to the functional elements of the claims below are intended to include any structures, materials, or acts for performing a function in combination with other claimed elements as specifically claimed. The description of one or more examples has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the disclosed forms. Numerous modifications and changes will be apparent to those skilled in the art. The examples have been selected and described in order to best explain various aspects and practical applications, and to enable others skilled in the art to understand the various examples with various modifications as suitable for the particular use contemplated.

[0246] It should be understood that all combinations of the above concepts and further concepts discussed in more detail below (provided such concepts are not mutually inconsistent) are contemplated as part of the inventive subject matter disclosed herein to achieve at least the advantages described herein. In particular, all combinations of the subject matter of the claims appearing at the end of this disclosure are contemplated as part of the subject matter disclosed herein. It should also be understood that the terms expressly used in this specification and which may also appear in any disclosures incorporated by reference are to be given the meaning most consistent with the particular concepts disclosed herein.

[0247] This written description uses examples to disclose the subject matter and enables any person skilled in the art to practice the subject matter, including making and using any device or system 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 include structural elements that do not differ from the literal words of the claims, or if they include equivalent structural elements that have insignificant differences from the literal words of the claims.

[0248] It should be understood that the above description is intended to be illustrative and not limiting. For example, the above-described examples (and / or aspects thereof) can be used in combination with each other. In addition, many modifications can be made to adapt a particular situation or material to the teachings of the various examples without departing from their scope. While the dimensions and types of materials described herein are intended to define the parameters of the various examples, they are in no way limiting and are provided merely as examples. Numerous other examples will become apparent to those skilled in the art upon review of the above description. The scope of the various examples should therefore be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. In the appended claims, the terms "including" and "in which" are used as the plain English equivalents of the respective terms "comprising" and "wherein." Moreover, in the following claims, the terms "first," "second," and "third," etc., are used merely as labels and are not intended to impose numerical requirements on their objects. As used herein, the term "based on" encompasses relationships where an element is partially based on, as well as relationships where an element is fully based on. The term "defined" encompasses relationships where an element is partially defined, as well as relationships where an element is fully defined. Furthermore, the limitations of the following claims are not written in means-plus-function form, and are not intended to be construed under 35 U.S.C. § 112, paragraph 6, unless such claim limitations expressly use the phrase "means for" followed by a description of a function without further structure. It is to be understood that not all such objects or advantages described above may necessarily be achieved in accordance with any particular embodiment of the present invention.Thus, for example, those skilled in the art will recognize that the systems and techniques described herein can be embodied or performed in a manner that achieves or optimizes one advantage or group of advantages taught herein without necessarily achieving other objectives or advantages that may be taught or suggested herein.

[0249] Although the subject matter has been described in detail with respect to only a limited number of examples, it should be readily understood that the subject matter is not limited to such disclosed examples. Rather, the subject matter can be modified to incorporate any number of variations, alterations, substitutions, or equivalent arrangements not heretofore described, but which are commensurate with the spirit and scope of the subject matter. Additionally, while various examples of the subject matter have been described, it should be understood that aspects of the disclosure may include only some of the described examples. Also, while some examples are described as having a certain number of elements, it will be understood that the subject matter can be practiced with fewer or more than that certain number of elements. Thus, the subject matter should not be deemed limited by the above description, but only by the scope of the appended claims.

Claims

1. 1. A method of forming a flow cell, comprising: applying a first adhesive to a substrate, the top surface of the substrate including electrical contacts; orienting a package on the first adhesive, the package including a die, a top surface of the die including an active surface and electrical contacts, and surfaces adjacent to the active surface on at least two opposite sides of the active surface forming fan-out regions for use in a fluid path of the flow cell; connecting the electrical contacts on the top surface of the substrate to electrical contact points on the die; applying a second adhesive to a portion of the package; and attaching a lid to the second adhesive, said attaching defining a fluid flow cell cavity beneath the lid and above a surface including the active surface and the fan-out region.

2. forming the package, the forming of the package further comprising: orienting the die onto the first adhesive; 2. The method of claim 1 , comprising: forming the fan-out region by orienting one or more support pieces on the first adhesive adjacent at least two sides of the die, the fan-out region including a portion of a top surface of the support piece.

3. 3. The method of claim 2, wherein the one or more support pieces include two support pieces, and wherein the orienting the one or more support pieces on the first adhesive adjacent the at least two sides of the die includes disposing two support pieces adjacent to the die on either side of the die.

4. 3. The method of claim 2, wherein the one or more support pieces include a single support piece, the single support piece including a notch, and wherein orienting the one or more support pieces on the first adhesive adjacent the at least two sides of the die includes orienting the single support piece such that the die and electrical contacts are within the notch.

5. The method of claim 1 , wherein the package comprises a cured electronic molding compound (EMC) material molded around a portion of the die, a portion of the EMC material comprising the fan-out region.

6. A flow cell comprising: a substrate including electrical contacts on a top surface thereof, the electrical contacts on the top surface of the substrate being connected to electrical contact points on a top surface of a die; A first curable adhesive, the first curable adhesive being bonded to a package, the package comprising: the die, the top surface of the die further comprising an active surface; a first cured adhesive including a fan-out region including a surface adjacent at least two opposing sides of the active surface, the fan-out region at least partially defining a fluid path of the flow cell; and a second curable adhesive that bonds a portion of a top surface of the package to a lid to define a fluid flow cell cavity beneath the lid and above a surface including the active surface and the fan-out region; and said lid.

7. The package comprises:

7. The flow cell of claim 6, further comprising one or more support pieces adjacent the at least two opposing sides of the active surface of the die, the one or more support pieces including the fan-out region.

8. 8. The flow cell of claim 7, wherein the one or more support pieces include two support pieces oriented on the at least two opposite sides of the active surface of the die.

9. 8. The flow cell of claim 7, wherein the one or more support pieces include a single support piece, the single support piece including a notch, and the die and the electrical contacts on the top surface of the substrate are oriented within the notch.

10. The package comprises: a hardened electronic molding compound (EMC) material molded around a portion of the die; a portion of the EMC material forming an EMC material surface adjacent the active surface on the at least two opposite sides of the active surface; The flow cell of claim 6 , wherein a portion of the EMC material surface comprises the fan-out region.

11. The package comprises: a hardened electronic molding compound (EMC) material molded around a portion of the die; and a layer deposited on the EMC material surface adjacent the at least two opposing active surfaces of the active surface, the fan-out region comprising a portion of the layer.

12. The flow cell of claim 10 or 11, wherein the package further comprises vias embedded in the EMC material.

13. 13. The flow cell of any one of claims 6 to 12, wherein the substrate further comprises electrical contacts on a bottom surface of the substrate, the electrical contacts on the bottom surface of the substrate being electrically coupled to the electrical contacts on the top surface of the substrate by vias formed through the substrate.

14. The flow cell of any one of claims 6 to 13, wherein the substrate further comprises a heating element.

15. The heating element is one or more resistors on one or more of the top surface of the substrate and the bottom surface of the substrate; a metal surface within the substrate; and a via through the substrate coupling the one or more resistors to the metal plane within the substrate.

16. The flow cell of claim 14 , wherein the heating element comprises a long wound metal trace within the substrate to function as a resistive heater.

17. A flow cell according to any one of claims 6 to 16, wherein the lid includes two openings, each opening defining one of an inlet fluid port or an outlet fluid port.

18. The flow cell of any one of claims 6 to 17, wherein the top surface of the die comprises a nanowell.

19. The flow cell of any one of claims 6 to 18, wherein the substrate comprises a material selected from the group consisting of glass reinforced epoxy laminate material, FR4, and co-fired ceramic sheets.

20. The flow cell of any one of claims 6 to 19, wherein the die is a complementary metal oxide semiconductor.

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