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 Art

[0003] Various protocols in biological or chemical research involve performing controlled reactions. Then, the specified reaction can be observed or detected, and subsequent analysis can assist in identifying or clarifying the properties of the chemical substances involved in the reaction. In some multiplex assays, an unknown analyte having 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 reaction that occurs between the known probe and the unknown analyte in the well can assist in identifying or clarifying 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] Some fluorescence detection protocols use an optical system to direct excitation light onto a fluorophore, such as a fluorescently labeled analyte, and to detect the fluorescence emission signal light that can be emitted from the analyte to which the fluorophore is attached. In other proposed detection systems, the controlled reaction within the flow cell is detected by a solid-state photosensor array (e.g., a complementary metal oxide semiconductor (CMOS) detector). These systems do not require large optical assemblies to detect fluorescence emission. The shape of the fluid channels within the flow cell can determine its usefulness for various applications; for example, SBS or annular array arrangement determination can be made within a sensor system utilizing multiple liquid flows, and therefore, fluid channel shapes of a particular shape can be utilized for SBS or annular array arrangement determination.

[0005] To enable SBS in the optical systems described above, some of the optical systems described provide electrical contacts to the sensor within the system (e.g., a CMOS used as a detector). In many such systems, a significant portion of the CMOS is occupied by the fluid path, minimizing the use of the sensor itself. To increase the size of the fluid channel to enhance the usability of the sensor, a region called a "fan-out" region can be created around the sensor. The fan-out region is the area packaged with the detector that extends horizontally beyond the detector. For example, if a CMOS sensor is used as a detector in a flow cell, the fan-out refers to the additional horizontal distance on both sides of the horizontal boundary of the CMOS sensor. [Overview of the project]

[0006] While using a fan-out region to form a flow cell can enhance the usability of the sensor because the fan-out region assists the fluidity of the flow cell, in some situations and examples of flow cells, preparing the surface of the fan-out region to meet the fluid requirements of the cell can be challenging from a manufacturing and fabrication standpoint. For example, in some cases, preparing a surface for use as a fan-out region may involve a grinding procedure that could damage the surface if the material constituting 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, expensive materials may be selected to meet the resistance requirements, which can increase the cost associated with the flow cell. Therefore, it may be beneficial to exclude this grinding process in flow cell fabrication.

[0007] Accordingly, the shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of a method for forming a flow cell. Various examples of the method are described below, and the methods, including and excluding the additional examples listed below, overcome these shortcomings in any combination (if these combinations are not contradictory). The method includes applying a first adhesive to a substrate such that the upper surface of the substrate includes electrical contacts; orienting a package on the first adhesive such that the package includes a die, the upper surface of the die includes an active surface and electrical contact points, and at least two surfaces adjacent to the active surface on opposite sides of the active surface form a fan-out region for use in the fluid path of the flow cell; connecting the electrical contacts on the upper surface of the substrate to the electrical contact points on the die; applying a second adhesive to a portion of the package; and attaching a lid to the second adhesive such that the lid defines a fluid flow cell cavity beneath the lid and on the surface including the active surface and the fan-out region.

[0008] In some examples, the method comprises forming a package, which comprises oriented a die onto a first adhesive and forming a fan-out region by oriented one or more support pieces onto the first adhesive adjacent to at least two sides of the die, wherein the fan-out region includes a portion of the upper surface of the support pieces.

[0009] In some examples, the arrangement of one or more support pieces includes two support pieces, and the orientation of one or more support pieces on the first adhesive adjacent to at least two sides of the die includes arranging two support pieces adjacent to the die on both sides of the die.

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

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

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

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

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

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

[0016] In some examples of methods for forming flow cells, forming a package further includes planarizing the surface of the EMC material adjacent to the active surface.

[0017] In some examples of methods for forming a flow cell, planarization includes depositing a layer on a surface including the top surface of the die and the EMC material surface adjacent to 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 layers include a photoresist.

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

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

[0021] In some examples of methods for forming a flow cell, the process of forming the package further involves embedding vias into the EMC material before curing the EMC material around the die portion.

[0022] In some examples of methods for forming flow cells, vias are made of conductive material.

[0023] In some examples of methods for forming flow cells, 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 in a direction opposite to the active surface, through the EMC material, from a surface opposite the active surface.

[0025] In some examples of methods of forming a flow cell, connecting an electrical contact on an upper surface of a substrate to an electrical contact point on a die includes wire bonding the electrical contact to the electrical contact point.

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

[0027] In some examples of methods of forming a flow cell, the method includes curing a first adhesive and a 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 of forming a flow cell, the substrate is a printed circuit board.

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

[0031] In some examples of methods of forming a flow cell, the substrate further includes an electrical contact on a bottom surface of the substrate, and the electrical contact on the bottom surface of the substrate is electrically coupled to an electrical contact on an upper surface of the substrate by a via formed through the substrate.

[0032] In some examples of methods of forming a flow cell, the method includes forming a heating element within the substrate.

[0033] In some examples of methods for forming a flow cell, forming a heating element involves placing one or more resistors on one or more of the top and bottom surfaces of a substrate, and coupling one or more resistors to a metal plane in the substrate via vias.

[0034] In some examples of methods for forming a flow cell, the heating element includes a long wound metal trace and is formed within the substrate so that it functions as a resistance heater.

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

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

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

[0038] In some examples of methods for forming flow cells, the active surface of the die contains nanowells.

[0039] The shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of a flow cell. Various examples of flow cells are described below, and the flow cells, including and excluding the additional examples listed below, overcome these shortcomings in any combination (if these combinations are not contradictory). The flow cell includes a substrate having electrical contacts on its upper surface, wherein the electrical contacts on the upper surface of the substrate are connected to electrical contact points on the upper surface of a die; a first curing adhesive, to which the first curing adhesive is bonded to a package, the package being a die, wherein the upper surface of the die further includes an active surface; a fan-out region, which includes a fan-out region, which includes a surface adjacent to at least two opposite sides of the active surface, wherein the fan-out region at least partially defines the fluid path of the flow cell; a second curing adhesive, which bonds a portion of the upper surface of the package to a lid, defining a fluid flow cell cavity beneath the lid and above the surface including the active surface and the fan-out region; and a lid.

[0040] In some examples of flow cells, the package comprises one or more support pieces adjacent to at least two opposite sides of the active surface of the die, wherein one or more support pieces further comprises one or more support pieces that include a fan-out region.

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

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

[0043] In some examples of flow cells, the package further comprises a cured electroformed compound (EMC) material molded around a portion of the die, and a portion of the EMC material forming an EMC material surface adjacent to at least two opposite sides of the active surface, wherein the portion of the EMC material surface includes a fan-out region.

[0044] In some examples of flow cells, the package includes a hardened electroformed compound (EMC) material molded around a portion of the die, and a layer deposited on the surface of the EMC material adjacent to the active surface on at least two opposite sides of the active surface, wherein the fan-out region includes a portion of the layer.

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

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

[0047] In some examples of flow cells, the substrate further includes electrical contacts on the bottom surface of the substrate, and these electrical contacts on the bottom surface of the substrate are electrically coupled to electrical contacts on the top surface of the substrate by vias formed through the substrate.

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

[0049] In some examples of flow cells, the heating element includes one or more resistors on one or more of the top and bottom surfaces of the substrate, a metal plane within the substrate, and vias through the substrate connecting one or more resistors within the substrate to the metal plane.

[0050] In some examples of flow cells, the heating element includes a long wound metal trace within the substrate so that it functions as a resistance heater.

[0051] In some examples of flow cells, the lid includes two openings, each defining either an inlet fluid port or an outlet fluid port.

[0052] In some examples of flow cells, 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 flow cells, the substrate includes a material selected from the group consisting of glass-reinforced epoxy laminate material, FR4, and co-fired ceramic sheet.

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

[0056] In some examples of flow cells, the substrate further includes electrical contacts on the bottom surface of the substrate, and these electrical contacts on the bottom surface of the substrate are electrically coupled to electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0057] The shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of a method for forming a flow cell. Various examples of the method are described below, and the methods, including and excluding the additional examples listed below, overcome these shortcomings in any combination (provided that these combinations are not contradictory). The method includes applying a first adhesive to a substrate such that the upper surface of the substrate includes electrical contacts; oriented a die onto the first adhesive such that the upper surface of the die includes an active surface and electrical contact points; forming a fan-out region for use in the fluid path of a flow cell, wherein forming the fan-out region involves oriented one or more support pieces onto the first adhesive adjacent to at least two sides of the die, such that a portion of the upper surface of the support pieces on at least two sides of the die includes the fan-out region; connecting electrical contacts on the upper surface of the substrate to electrical contact points on the die; applying a second adhesive to a portion of one or more support pieces; and attaching a lid to the second adhesive such that attaching defines a fluid flow cell cavity beneath the lid and on a surface including the active surface and the fan-out region.

[0058] In some examples, the arrangement of one or more support pieces includes two support pieces, and the orientation of one or more support pieces on the first adhesive adjacent to at least two sides of the die includes arranging two support pieces adjacent to both sides of the die.

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

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

[0061] In some examples, forming a heating element involves mounting long wound metal traces within the substrate so that they function as a resistance heater.

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

[0063] The shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of flow cells. Various examples of flow cells are described below, including and excluding the additional examples listed below, and any combination of flow cells (where these combinations are not contradictory) overcome these shortcomings. The flow cell includes a substrate having electrical contacts on its upper surface, wherein the electrical contacts on the upper surface of the substrate are connected to electrical contact points on the upper surface of a die; a first curing adhesive, the first curing adhesive bonding the die and one or more support pieces adjacent to at least two sides of the die to the substrate, such that a portion of the upper surface of the die and a portion of the upper surface of one or more support pieces form a surface utilized in the fluid path of the flow cell; a second curing adhesive, the second curing adhesive bonding an area of ​​one or more support pieces and an area of ​​the upper surface of the die adjacent to the surface utilized in the fluid path of the flow cell to a lid; and a lid, the lid defining a fluid 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, one or more support pieces include two support pieces oriented on either side of the die.

[0065] In some examples of flow cells, the substrate further includes electrical contacts on the bottom surface of the substrate, and these electrical contacts on the bottom surface of the substrate are electrically coupled to electrical contacts on the top surface of the substrate by vias formed through the substrate.

[0066] The shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of a method for forming a flow cell. Various examples of the method are described below, and the methods, including and excluding the additional examples listed below, overcome these shortcomings in any combination (provided that these combinations are not contradictory). The method includes applying a first adhesive to a substrate such that the upper surface of the substrate includes electrical contacts; oriented a die onto the first adhesive such that the upper surface of the die includes an active surface and electrical contact points; forming a fan-out region for use in the fluid path of a flow cell, the formation of the fan-out region includes oriented two support pieces onto the first adhesive on both sides of the die such that each of the two support pieces is adjacent to the die, and the upper surface of the die and the upper surfaces of the two support pieces form an upper surface; discharging material to fill the gap between the two support pieces and the die; connecting electrical contacts on the upper surface of the substrate to 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 such that the attachment defines a fluid flow cell cavity beneath the lid and on the upper surface.

[0067] The shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of a method for forming a flow cell. Various examples of the method are described below, and the methods, including and excluding the additional examples listed below, overcome these shortcomings in any combination (if these combinations are not contradictory). The method comprises applying a first adhesive to a substrate, wherein the upper surface of the substrate includes electrical contacts; oriented a die onto the first adhesive, wherein the upper surface of the die includes an active surface and electrical contact points; forming a fan-out region for use in the fluid path of a flow cell, wherein oriented a support piece onto the first adhesive, wherein the support piece includes a notch, and oriented the support piece onto the first adhesive such that the die and electrical contacts are positioned within the notch, wherein the fan-out region is on both sides of the die Forming includes oriented the upper surface portion of the support piece, the upper surface portion and the active surface to form an upper surface; connecting the electrical contacts on the upper surface of the substrate to the electrical contact points on the die with bond wires; discharging the second adhesive into the notch so that the second adhesive fills the space in the notch 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 the lid to the third adhesive, the attachment defining a fluid flow cell cavity beneath the lid and on the upper surface.

[0068] The shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of a method for forming a flow cell. Various examples of the method are described below, and the methods, including and excluding the additional examples listed below, overcome these shortcomings in any combination (provided that these combinations are not contradictory). The method comprises applying a first adhesive to a substrate such that the top surface of the substrate includes electrical contacts; oriented a package comprising a cured electroformed compound (EMC) material molded around a portion of a die such that the top surface of the die includes an active surface and electrical contact points, and a portion of the EMC material forms EMC material surfaces adjacent to at least two opposite sides of the active surface; connecting 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 top surface of the package; and attaching a lid to the second adhesive such that the attachment defines a fluid flow cell cavity below the lid and on a surface including an active surface and a fan-out region for use in the 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 consists of at least two EMC material surfaces adjacent to the active surface on opposite sides of the active surface.

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

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

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

[0073] In some examples, the substrate further includes electrical contacts on its bottom surface, and these electrical contacts on the bottom surface of the substrate are electrically coupled to 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, and forming the package includes curing an EMC material around a portion of the die.

[0075] The shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of flow cells. Various examples of flow cells are described below, including, and excluded from, the flow cells, in any combination (where these combinations are not contradictory), overcome these shortcomings. The flow cell includes a substrate having electrical contacts on its upper surface, the electrical contacts on the upper surface of the substrate being connected to electrical contact points on the upper surface of the die; a first curing adhesive, the first curing adhesive bonding a package comprising a cured electroformed compound (EMC) material molded around a portion of the die, the upper surface of the die being exposed and including an active surface and electrical contacts, a portion of the EMC material forming EMC material surfaces adjacent to the active surface on at least two opposite sides of the active surface, and a portion of the EMC material surfaces including a fan-out region for use in the fluid path; a second curing adhesive, the second curing adhesive bonding a portion of the upper surface of the package to a lid, defining a fluid flow cell cavity beneath 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 can be overcome as described below, and the benefits and advantages can be achieved through the provision of flow cells. Various examples of flow cells are described below, including and excluding the additional examples listed below, and any combination of flow cells (where these combinations are not contradictory) overcome these shortcomings. The flow cell includes a substrate having electrical contacts on its upper surface, the electrical contacts on the upper surface of the substrate being connected to electrical contact points on the upper surface of the die; a first curing adhesive, the first curing adhesive bonding a package comprising a cured electroformed compound (EMC) material molded around a portion of the die, the upper surface of the die being exposed and including an active surface and electrical contact points, a portion of the EMC material forming EMC material surfaces adjacent to the active surface on at least two opposite sides of the active surface, the layer planarizing the EMC material surfaces, the portion of the EMC material surfaces planarized by the layer including a fan-out region for use in the fluid path; a second curing adhesive, the second curing adhesive bonding a portion of the upper surface of the package to a lid, defining a fluid flow cell cavity beneath the lid and above the surface including the active surface and fan-out region; and a lid.

[0078] The shortcomings of the prior art can be overcome as described below in this disclosure, and the benefits and advantages can be achieved through the provision of methods for forming elements usable in one or more flow cells. Various examples of the methods are described below, and the methods, including and excluding the additional examples listed below, overcome these shortcomings in any combination (provided these combinations are not contradictory). The method comprises assembling a package comprising a cured molding material surrounding a portion of one or more dies, wherein one or more pillars of a first conductive material are embedded in the molding material, assembling is: applying a temporary adhesive to the surface of a carrier; oriented one or more pillars on the adhesive; oriented one or more dies on the adhesive such that one or more pillars are oriented between each of the one or more dies, wherein each one or more pillar has a vertical length greater than each of the one or more dies; molding is formed around the top surface of the carrier and the surfaces of one or more dies and one or more pillars such that the top surface of the mold has a vertical length greater than one or more pillars, wherein the top surface of the mold is parallel to the surface of the carrier; curing the molding material; grinding the top surface of the mold to expose the top surfaces of one or more pillars and one or more dies to create new surfaces; plating the top surfaces of one or more pillars with a second conductive material to create a seed layer; and one or more redistribution layers. Coating a layer (RDL), wherein each RDL coating includes patterning a layer on a new surface, opening a portion of the layer to form an opening, and spreading the third conductive material into each opening so that the third conductive material spreads through the opening and electrically couples to the seed layer; attaching electrical contacts to a portion of the third conductive material in the opening 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 the surface of one or more dies exposed by removing the carrier and temporary adhesive to create an active surface, and plating the 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 involves electrically coupling electrical contacts on a pillar to a portion of the surface of one or more dies containing a chemical substance.

[0081] In some examples, the method for electrically coupling electrical contacts on a pillar to a portion of the surface of one or more dies containing chemicals is selected from the group consisting of wire bonding and printing.

[0082] In some examples, the method involves attaching one or more lids to the package surface, with the fluid flow cell cavity defined beneath each of the one or more lids and on the surface of each of the corresponding one or more sensors, which include 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 cases, attaching one or more lids involves applying adhesive to a portion of the package surface.

[0086] In some examples, opening up a portion of a layer to form an opening involves utilizing photolithography.

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

[0088] In some examples, oriented one or more pillars and one or more dies involves using a pick-and-place tool.

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

[0090] The shortcomings of the prior art can be overcome as described below, and the benefits and advantages can be achieved through the provision of flow cells. Various examples of flow cells are described below, including and excluding the additional examples listed below, in any combination (if these combinations are not contradictory), these shortcomings are overcome. A flow cell includes a package comprising a cured material molded around a portion of a die, wherein one or more pillars of a first conductive material are embedded in the molded material, and the top surface of the package comprises the active surface of the die; and a lid attached to a portion of the top surface of the package, wherein 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 the bottom of the package. The RDLs include openings filled with a conductive material that are electrically coupled to at least one of the one or more pillars.

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

[0093] In some cases, the curing material includes an electroforming compound (EMC).

[0094] Further features are realized through the techniques described herein. Other examples and embodiments are described in detail herein and are considered part of the claimed embodiments. These and other purposes, features, and advantages of this disclosure will become apparent from the following detailed descriptions of the various embodiments of this disclosure, made in conjunction with the accompanying drawings.

[0095] It should be understood that all combinations of the aforementioned embodiments and additional concepts, which are discussed in more detail herein, (provided that such concepts are not contradictory) are considered to be part of the subject matter of the invention and to realize the advantages disclosed herein. [Brief explanation of the drawing]

[0096] One or more embodiments are specifically identified and explicitly claimed in the conclusion of the specification as examples of the claims. The aforementioned content and purpose, features and advantages of one or more embodiments are evident from the following detailed description, which is made in conjunction with the accompanying drawings. [Figure 1] The assembly diagram and exploded view of a flow cell having a fan-out region are shown, respectively. The fan-out region is formed by assembling a sensor or detector on a substrate using one or more support pieces. [Figure 2] The assembly diagram and exploded view of a flow cell having a fan-out region are shown, respectively. The fan-out region is formed by assembling a sensor or detector on a substrate using one or more support pieces. [Figure 3] Figures 1 and 2 show the top and bottom views of the flow cell, respectively. [Figure 4] Figures 1 and 2 show the top and bottom views of the flow cell, respectively. [Figure 5] Figures 1 and 3 show the process flow illustrating the stepwise formation of the flow cells. [Figure 6] This is a workflow showing how to form the flow cells shown in Figures 1 and 3. [Figure 7] Figures 2 and 4 show the process flow illustrating the stepwise formation of the flow cells. [Figure 8] This is a workflow showing how to form the flow cells shown in Figures 2 and 4. [Figure 9] A side view of an example of a flow cell is shown, specifically illustrating a heating element that can be integrated into the examples discussed herein. [Figure 10]The assembly and exploded views of the flow cell, including the package containing the material molded around the sensor or detector, are shown, respectively. [Figure 11] The assembly and exploded views of the flow cell, including the package containing the material molded around the sensor or detector, are shown, respectively. [Figure 12] Figures 10 and 11 show a side view of one of the packages shown. [Figure 13] Figures 10 and 11 show a side view of one of the packages shown. [Figure 14] Figures 10 and 11 show the top and bottom views of the flow cell, respectively. [Figure 15] Figures 10 and 11 show the top and bottom views of the flow cell, respectively. [Figure 16] Figures 10 and 14 show the process flow illustrating the stepwise formation of the flow cells. [Figure 17] This is a workflow showing how to form the flow cells in Figures 10 and 14. [Figure 18] Figures 11 and 15 show the process flow illustrating the stepwise formation of the flow cells. [Figure 19] This is a workflow showing how to form the flow cells shown in Figures 11 and 15. [Figure 20] Figures 10-11 and 14-15 show side views of an example of a flow cell having the elements of the flow cell, and specifically illustrate heating elements that can be integrated into the examples discussed herein. [Figure 21] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 22] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 23] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 24] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 25] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 26] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 27] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 28] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 29] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 30] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 31] Figures 10-11 and 14-15 show a process flow illustrating the stepwise formation of a flow cell, including a specific embodiment of the package shown in the flow cell. [Figure 32] This is a workflow showing how to form the flow cell shown in Figure 31. [Modes for carrying out the invention]

[0097] The accompanying drawings, which are incorporated herein and form part thereof, and which refer to the same or functionally similar elements across separate figures with the same reference numerals, further illustrate the present implementation and serve to explain the principles of the present implementation, along with a detailed description of the implementation. As will be understood by those skilled in the art, the accompanying drawings are provided for ease of understanding and illustrate specific examples of the present implementation. The implementation is not limited to the examples shown in the figures.

[0098] The terms “connect,” “connected,” “contact,” and “coupled” are defined broadly herein to encompass a variety of different arrangement and assembly techniques. These arrangements and techniques include, but are 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 with each other), and (2) connecting one component to another with one or more components between them, provided that one component that is “connected,” “contacted,” or “coupled” to the other component is in some operational communication (e.g., electrical, fluid, physical, optical, etc.) with the other component (despite 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 electrically connected, electrically coupled, optically connected, optically coupled, fluidically connected, or fluidly coupled components may or may not be in direct physical contact, and one or more other components may be positioned between them.

[0099] As used herein, the terms “including” and “comprising” have the same meaning.

[0100] The terms “substantially,” “approximately,” “about,” “relatively,” or other similar terms, which may be used throughout this disclosure including the claims, are used to describe and consider small variations from a standard or parameter, such as those resulting from variations in processing. Such small variations include zero-point variations from the standard or parameter. For example, they may refer to ±10%, such as ±5%, ±2%, ±1%, ±0.5%, ±0.2%, ±0.1%, ±0.05%, etc. When used herein, the terms “substantially,” “approximately,” “about,” “relatively,” or other similar terms may also refer to no variation, i.e., ±0%.

[0101] As used herein, “flow cell” may include a device having a lid that extends over a reaction structure and forms flow channels between them communicating with a plurality of reaction sites of the reaction structure, and may include a detection device for detecting a specified reaction occurring at or near the reaction site. The flow cell may include a solid-state physical photodetector or “imaging” device, such as a charge-coupled device (CCD) or complementary metal-oxide-semiconductor (CMOS) (optical) detection device. As one specific example, the flow cell may be hydrodynamically and electrically coupled to a cartridge (having an integrated pump) which can be hydrodynamically 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 a plurality of imaging events. For example, the cartridge and / or bioassay system can guide one or more reaction solutions through the flow channels of the flow cell and thereby along the reaction site. At least one of the reaction solutions may contain four different nucleotides having the same or different fluorescent labels. In some examples, nucleotides bind to a reaction site in the flow cell, such as a corresponding oligonucleotide at the reaction site. In these examples, the cartridge and / or bioassay system then illuminates the reaction site using an excitation light source (e.g., a solid-state light source such as a light-emitting diode (LED)). In some examples, the excitation light has a predetermined wavelength or multiple wavelengths, including a range of wavelengths. The fluorescent label excited by the incident excitation light can provide an emission signal (e.g., one or more wavelengths of light different from the excitation light and potentially different from each other) that can be detected by a photosensor in 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 events, properties, qualities, or features that exhibit a specified reaction. For example, the flow cells described herein include, or can be integrated with, photodetection devices, sensors including but not limited to biosensors, and their components, as well as bioassay systems that operate with sensors including biosensors.

[0103] A flow cell facilitates multiple specified reactions that can be detected individually or collectively. The flow cell performs numerous cycles in which multiple specified reactions occur in parallel. For example, a flow cell can be used to sequence a high-density array of DNA features through repeated cycles of enzyme manipulation and light or image detection / capture. Thus, the flow cell can be fluidly connected to one or more microfluidic channels that deliver reagents or other reaction components in the reaction solution to the reaction sites in the flow cell. The reaction sites can be provided or separated in a predetermined manner, such as a uniform or repeating pattern. Alternatively, the reaction sites can be randomly distributed. Each reaction site can be associated with one or more optical guides and one or more optical sensors that detect light from the associated reaction site. In one example, the optical guide includes one or more filters for filtering specific wavelengths of light. The optical guide can be an absorption filter (e.g., an organic absorption filter), for example, such that the filter material absorbs a specific wavelength (or wavelength range) and allows at least one predetermined wavelength (or wavelength range) to pass through it. In some flow cells, the reaction site may be located within a reaction recess or chamber that can at least partially compartmentalize the specified reaction.

[0104] As used herein, “specified reaction” includes a change in at least one of the chemical, electrical, physical, or optical properties (or qualities) of a subject chemical or biological substance, such as a sample. In a particular flow cell, the specified reaction is a positive binding event, such as the incorporation of a fluorescently labeled biomolecule with the subject. More generally, the specified reaction may be a chemical transformation, chemical change, or chemical interaction. The specified reaction may also be a change in electrical properties. In a particular flow cell, the specified reaction includes the incorporation of a sample with a fluorescently labeled molecule. The sample may be an oligonucleotide, and the fluorescently labeled molecule may be a nucleotide. The specified reaction may be detected when excitation light is directed at the oligonucleotide having the labeled nucleotide, and the fluorophore emits a detectable fluorescence signal. In another example of a flow cell, the detected fluorescence is the result of chemiluminescence or bioluminescence. The specified reactions can also increase fluorescence (or Forster) resonance energy transfer (FRET) by, for example, bringing a donor fluorophore close to an acceptor fluorophore, decrease FRET by separating the donor and acceptor fluorophore, increase fluorescence by separating a quencher from the fluorophore, or decrease fluorescence by colocalizing the quencher and fluorophore.

[0105] As used herein, “electrically coupled” and “optically coupled” refer to the transmission of electrical energy and light waves, respectively, between any combination of power sources, electrodes, conductive parts of substrates, droplets, conductive traces, wires, waveguides, nanostructures, and other circuit segments. The terms “electrically coupled” and “optically coupled” may be used in reference to direct or indirect connections that can pass through various media such as fluid media and air gaps.

[0106] As used herein, “reaction solution,” “reacting component,” or “reacting substance” includes any substance that can be used to obtain at least one specified reaction. For example, potential reacting components include reagents, enzymes, samples, other biomolecules, and buffers. Reacting components can be delivered in solution to a reaction site in a flow cell disclosed herein and / or immobilized on the reaction site. Reacting components can interact directly or indirectly with other substances, such as a sample immobilized on the reaction site of the flow cell.

[0107] As used herein, the term “reaction site” refers to a localized region on which at least one specified reaction may occur. A reaction site may include a reaction structure or a supporting surface of a substrate on which a substance can be immobilized. For example, a reaction site may include the surface of a reaction structure (which may be located within a channel of a flow cell) on which a reaction component, for example, a colony of nucleic acid, is located. In some flow cells, the nucleic acids in the colony have the same sequence and are, for example, clone copies of a single-stranded or double-stranded template. However, in some flow cells, the reaction site may contain only a single nucleic acid molecule, for example, 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 within a package. For example, in the case where a CMOS sensor is used as a detector within a flow cell, the active surface is a portion of the surface of the CMOS sensor that includes nanowells. Throughout this disclosure, the terms die and wafer are also used in relation to the specific 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 the detector that extends horizontally beyond the detector itself. For example, when a CMOS sensor is used as a detector in a flow cell, 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 illustrated and described herein. Where the terms “pillar bump” or “bump” are used, various examples of electrical contacts may also be used in various examples of the devices illustrated herein. Pillar bumps or what may be bumps may include conductive materials such as metallic materials (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum), or combinations thereof), but it is understood that other conductive materials may be used.

[0111] For the sake of clarity, diagrams are provided below, but they are not drawn to scale, and the same reference numbers are used across different diagrams to represent 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 therefore the active surface, the sensor area itself, may not be fully utilized. Flow cells can be formed with fan-out regions so that the entire surface of the sensor can be utilized more efficiently and completely as a sensor or detector, in order to move some of the fluid function away from the active surface. However, certain techniques for forming the fan-out regions can not only increase costs but also contribute to the complexity associated with the formation of the flow cell. These techniques may also impose certain limitations on the type of material that can 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 region, and expensive substrates (or carriers) may be used to withstand this process. The examples described herein illustrate methods for forming flow cells, the resulting flow cells being formed by using materials used for printed circuit boards (PCBs) (e.g., glass, silicon, ceramics, etc.) as the substrate, which are generally understood to be less expensive than those used in the examples involving the grinding process described above.

[0113] The examples described herein do not utilize the grinding process described above, but allow for variations in the substrate material. In the examples herein, the fan-out region is formed by assembling a sensor or detector on the substrate, as shown in the following figures. In these examples, the fan-out region itself is formed by a variety of methods, including, but not limited to, the following: 1) assembling support pieces (e.g., glass, silicon, and ceramic) on the substrate, with a portion of the support pieces forming the fan-out region, and / or 2) packaging a sensor (e.g., a CMOS image sensor die) by molding an electro-molded compound (EMC) material (epoxy mold compound) around it, with a portion of the EMC material forming the fan-out region. In the latter example, the EMC molded around the die may or may not be embedded with vias (e.g., copper vias) for heat conduction. In these examples, the substrate is a PCB. In some examples, a PCB substrate can incorporate an internal heating mechanism, achieved by utilizing at least two methods, including but not limited to those described herein: 1) implementing a heat diffusion plane by placing power resistors on one or more of the top or bottom of the PCB substrate so that heat is transferred to a metal plate within the substrate by vias (e.g., conductive vias, metal vias, etc.) to desired locations, and the (currently) heated metal plate diffuses the heat to maintain a uniform and / or near-uniform temperature distribution at the desired locations; and / or 2) implementing resistive paths by utilizing interconnects within the PCB as a heat source by embedding (e.g., long winding) traces at desired locations to generate heat through the resistance of each path. In various examples, the spreader plane and / or resistive paths may be separated into different zones on the substrate so that the substrate contains different temperature zones, which can be individually adjusted.

[0114] This specification describes various examples of flow cells that utilize support pieces as fan-out regions and methods for forming such flow cells, as well as various examples of flow cells that utilize EMC materials as fan-out regions and methods for forming such flow cells. Figures 1 to 9 show various elements and embodiments of examples of flow cells formed by utilizing support pieces and assembling sensors or detectors on a PCB substrate. Figures 10 to 20 show various elements and embodiments of examples of flow cells formed by assembling a package containing sensors or detectors and EMC materials on a PCB substrate, and Figures 21 to 32 show the formation of some examples of EMC and sensor or detector packages that may be included in the flow cells described in Figures 10 to 20, at least in part.

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

[0116] Referring first to Figure 1, this figure includes two diagrams of the flow cell 100: an assembly diagram 125 on the left and an exploded view 135 on the right. As shown in this example, the detector or sensor (e.g., CMOS) 180 is mounted on a PCB substrate 150. In some examples, the detector or sensor 180 is a CMOS image sensor having a patterned nanowell structure on its top surface (e.g., on the active surface). The PCB substrate 150 may consist of 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 is clear from exploded view 135, the detector or sensor (e.g., CMOS) 180 is mounted on the PCB substrate 150 using a film or adhesive 140, which similarly mounts support pieces 130 on both sides of the detector or sensor (e.g., CMOS) 180 to form a fan-out region. In some examples, the adhesive is extruded and / or coated with a film that attaches the detector or sensor 180 and the adjacent support piece 130 to the substrate 150. This film or adhesive 140 can be thermocured and / or ultraviolet (UV) cured. The materials that can constitute these support pieces 130 may include, but are not limited to, glass, silicon, and ceramic. A lid (e.g., glass) 110 is attached using another film or adhesive 120. This film or adhesive 120 can be extruded or formed as a film to attach the lid 110 to the detector or sensor 180 (e.g., a CMOS die) and the fan-out support piece 130. The space beneath the lid 110 and above the active (top) surface of the detector or sensor (e.g., CMOS) 180 and the upper surface (not covered by the film or adhesive 120) of the portion of the support piece 130 forms a flow path. The lid 110 defines a fluid flow cell cavity having inlet and outlet fluid ports 105. Contacts (not shown) on the active surface of a detector or sensor (e.g., CMOS) 180 are wire-bonded 170 to electrical connection parts (e.g., bond pads, contact pads) 160 on a PCB substrate 150.In some examples, the electrical connection 160 is a metal bond pad located on the upper surface of the PCB substrate 150, enabling wire bonding to the bond pad on the upper surface of the detector or sensor 180 (e.g., a CMOS die).

[0117] As seen in Figure 2, the difference between the flow cell 100 in Figure 1 and the flow cell 200 in Figure 2 is that in Figure 2, a single support piece 230 is used to form fan-out regions 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 having a patterned nanowell structure on its top (e.g., on the active surface). To correspond to the difference in the support structure 230 used to form the fan-out regions, the film or adhesive 240 used to attach the detector or sensor (e.g., CMOS) 280 to the PCB substrate is made into a different shape. As is more apparent in exploded view 235, the detector or sensor (e.g., CMOS) 280 is attached to a PCB substrate 250, which may include an internal heater (not shown), using the film or adhesive 240. The PCB substrate 150 may consist of standard PCB lamination materials, including but not limited to glass-reinforced epoxy lamination materials such as FR4 and / or co-fired ceramic sheets. The film or adhesive 240 is also used to attach a support piece 230 surrounding the detector or sensor (e.g., CMOS) 280. The support piece 280 includes a notch 265 for housing the detector or sensor (e.g., CMOS) 280, and 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 the 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, allowing 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 made of a material including, but not limited to, glass, silicon, and ceramic. A lid (e.g., glass) 210 is attached using another film or adhesive 220. This film or adhesive 220 can be extruded or formed as a film so that the lid 210 can be attached to the detector or sensor 280 (e.g., a CMOS die) and the fan-out support piece 230.The space beneath the lid and above the active (top) surface of the detector or sensor (e.g., CMOS) 280 and the upper surface of the portion of the support piece 230 (either not covered by the film or adhesive 220 or covered by the lid 210) forms a flow path. The lid 210 also defines a fluid flow cell cavity having inlet and outlet fluid ports 205.

[0118] Figure 3 shows top view 145 and bottom view 155 of the flow cell 100. The flow cell 100 is also shown in Figure 1. The bottom view 155 of the flow cell 100, specifically of the substrate 150, shows electrical contacts 167 which may include pads containing pogo pins (called pogo pads). These electrical contacts 167 enable electrical connection to the receiving socket and / or device of the flow cell 100 (specifically, ultimately to the detector or sensor 180). As shown in later figures, vias and / or various other conductive elements formed across the PCB substrate 150 connect electrical contacts 160 to 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 is translucent in this example and may be made of glass) are the inlet and outlet fluid ports 105. Beneath the lid 110, there is a fan-out region formed as shown in Figure 1, which has a support piece 130 and is not visible from any of the views in Figure 4.

[0119] Referring to Figure 4, which shows a top view 245 and a bottom view 255 of the flow cell 200, this flow cell 200 is also shown in Figure 2. The bottom view 255 of the flow cell 200, specifically the substrate, shows electrical contacts 267 which may include pads containing pogo pins (called pogo pads). These electrical contacts 267 enable electrical connection of the flow cell 200 (specifically, the detector or sensor 280) to the receiving socket and / or fixture. As shown in later figures, vias and / or various other conductive elements formed across the PCB substrate 250 connect electrical contacts 260 to 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 is translucent in this example and may be made of glass) are the inlet and outlet fluid ports 205. In contrast to the examples in Figures 1 and 3, in Figure 4, the flow cell 200 utilizes a single support piece 230 with a cutout for housing a detector or sensor 280 and electrical contacts 260, so that the portion of the support piece 230 is not covered by the lid 210, but rather extends longitudinally beyond the boundary of the lid 210 in this case. The fan-out regions formed from the portion of the single support piece 230 are not visible from any view of Figure 4 because they are under the lid 210.

[0120] Figure 5 shows a workflow 500 illustrating exemplary embodiments in the formation of several examples of flow cells, including but not limited to the flow cell 100 shown in Figures 1 and 3. Reference numbers used in workflow 500 to refer to various embodiments of flow cell 100 are provided for illustrative purposes throughout this process flow 500 and do not imply any limitations. In Figure 5, for example, a substrate 150 is fabricated (505) having electrical contacts such as pogo pads at the bottom (e.g., Figure 3, 167) and electrical contacts 160 (e.g., wire bond pads) at the top. In some examples, the substrate includes an integrated heater assembly (not shown in Figure 5). The bottom electrical contacts (e.g., Figure 3, 167) and the top electrical contacts 160 are connected to each other via connectors, including but not limited to vias, on the substrate 150. As previously stated, the substrate 150 may be fabricated from standard PCB lamination 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 the upper part of the substrate 150. The detector or sensor 180 (e.g., a CMOS die) is oriented onto the adhesive and / or film 140 between the electrical contacts 160 (525). 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 to the detector or sensor 180 to form a fan-out region (535). When forming the fan-out region, the gaps between each part of the support piece 130 and the detector or sensor 180 may be filled and cured with, for example, a liquid dispensing adhesive (to create a uniform surface for the fluid function of the flow cell 200). The electrical contacts 160 are then wire-bonded to the electrical contacts (not shown) on the detector or sensor 180 (e.g., a CMOS die) (545). For example, the wire 170 may be coupled 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 between them. After the wire has been used to connect the electrical contacts to each other, the connection may be encased in epoxy.In some cases, this epoxy protection for electrical connections may be added after the lid 110 is secured to the flow cell 100.

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

[0122] Figure 6 shows workflow 600, which is similar to the process in Figure 5. Referring to Figure 6, a substrate is fabricated having electrical contacts on the bottom surface and electrical contacts on the top surface (these are connected via the substrate using vias or other such connections) (605). Adhesive and / or film is applied to the substrate between the electrical contacts on the top surface of the substrate (615). The detector or sensor (e.g., a CMOS die) is oriented on the adhesive and / or film between the electrical contacts (625). 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). When forming the fan-out region, the gaps between each part of the support piece and the detector or sensor may be filled and cured, for example, with liquid dispensing adhesive. The electrical contacts on the top surface of the substrate are wire-bonded to the electrical contacts on the active surface (top surface) of the detector or sensor (645). These wire-bonded connections may be protected after formation by applying 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). The lid is attached to the adhesive and / or film, defining a fluid flow cell cavity with inlet and outlet fluid ports (665). Both the first and second adhesives and / or films are cured at some point after they have been applied and utilized to form the attachment.

[0123] Figure 7 shows a workflow 700 illustrating exemplary embodiments in the formation of several examples of flow cells, including but not limited to the flow cell 200 shown in Figures 2 and 4. Unlike the flow cell 100 in Figures 1 and 3, the flow cell 200 in Figures 2 and 4 includes a single support piece 230 for forming a fan-out region. The reference numbers used in workflow 700 refer to various embodiments of the flow cell 200 for illustrative purposes and do not introduce any limitations. In Figure 5, for example, a substrate 250 is fabricated having electrical contacts such as pogo pads at the bottom (e.g., Figure 4, 267) and electrical contacts 260 at the top (e.g., wire bond pads) (705). In some examples, the substrate includes an integrated heater assembly (not shown in Figure 7). The bottom electrical contacts (e.g., Figure 4, 267) and the top electrical contacts 260 are connected to each other via connectors, including but not limited to vias, on the substrate 250. As described above, 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 extruded and / or coated onto the substrate 250 (715). The adhesive and / or film 240 extends beyond the electrical contacts 260 but is not formed on the electrical contacts 260 (to allow the electrical contacts 260 to be wire-bonded or otherwise connected to the 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 wire 270 may be coupled to electrical contacts 260 (e.g., wire bond pads) (these electrical contacts are not shown) on the substrate 250 and on the detector or sensor 280 (e.g., CMOS die) to form an electrical connection between them. After being used to connect the wire and the electrical contacts to each other, an adhesive (e.g., epoxy) is dispensed into the cavity surrounding the detector or sensor 280 to seal the bond wire and fill the gaps on both sides of the detector or sensor 280 (e.g., CMOS die) by capillary action, and another adhesive and / or film 220 is dispensed or applied to a portion of the support piece 230 and the periphery of the detector or sensor 280 (e.g., CMOS die) (755). The lid 210 is attached to this adhesive and / or film 220 (765). The space beneath the lid 210 and above the active (top) surface of the detector or sensor (e.g., CMOS) 280 and the upper surface of the portion of the support piece 230 (which is not covered by the film or adhesive 120 but is covered by the lid 210) forms a flow path. The lid 210 also defines a fluid flow cell cavity having inlet and outlet fluid ports 205. The fluid ports 205 are inlet and outlet openings within the lid 210.

[0124] Figure 8 shows workflow 800, which is similar to the process in Figure 7. Referring to Figure 8, a substrate is fabricated having electrical contacts on the bottom and electrical contacts on the top (these are connected through the substrate using vias or other such connections) (805). Adhesive and / or film is applied to the substrate (815). The detector or sensor (e.g., a CMOS die) is oriented on the adhesive and / or film between the electrical contacts that are not covered by the adhesive and / or film (825). A cutout for housing the detector or sensor, as well as a support piece containing 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). Adhesive (e.g., epoxy) is dispensed into the cavity surrounding the detector or sensor to seal the bond wires and fill the gaps on both sides 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). The lid is attached to the adhesive and / or film, defining a fluid flow cell cavity with inlet and outlet fluid ports (865). Both the first and second adhesives and / or films are cured at some point after they have been applied and utilized to form the attachment.

[0125] Referring now to Figure 9, as previously stated, some examples of flow cells formed using some aspects of the method described herein are formed on a substrate containing various heating elements. Figure 9 shows a flow cell 100 in a side view 900, similar to the flow cell 100 in Figures 1 and 3, with this detail added to the substrate 150. Numbering consistency is provided for illustrative purposes. The flow cells 200 in Figures 2 and 4 share substantially the same elements and may save a single support piece 230 (see Figures 2 and 4) surrounding the detector or sensor 280 on all four sides. Although Figure 9 does not overlap with the reference numbers for the flow cells in Figures 2 and 4, the generally named elements are relevant to both configurations.

[0126] The flow cell 100 in Figure 9 includes various embodiments as seen in other figures. For example, the flow cell 100 includes at least two support pieces 160 on either side of the detector or sensor 180. The support pieces 106 allow 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 having a patterned nanowell structure 177 on top. 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 extruded or coated as a film to fabricate this attachment and then cured (e.g., thermosetting or UV curing). 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 on its bottom surface 167. In this example, the electrical connections on the top surface 160 are bond pads (e.g., metal), allowing wire bonding to the bond pads on the top surface of the detector or sensor 180 (e.g., CMOS die). On the other hand, the electrical connections on its bottom surface 167 are pogo pads, allowing electrical connections to a receiving socket or device. The flow cell 100 contains a fluid, and the glass lid 110 defines a fluid flow cell cavity having inlet and outlet fluid ports 105. The lid 110 (e.g., glass) is attached to the support piece 160 and part of the detector or sensor 180 with adhesive 120. Like the adhesive and / or film 140, this adhesive or film 120 can also be dispensed or applied as a film. The adhesive or film 120 can then be cured (e.g., thermosetting or UV curing).

[0127] The substrate 150 in Figure 9 has an embedded heater for controlling the package temperature. As previously mentioned, some or all of these elements can also be integrated into the flow cell 200 examples in Figures 2 and 4. In the flow cell 100 of Figure 9, heating can be achieved by one or more of two methods. Firstly, a power resistor 152 may be placed on the top or bottom of the substrate 150, and heat is transferred to a desired location by vias 159, and a metal plane 153 spreads the heat over a desired area to maintain a uniform temperature. Secondly, a long wound metal trace 156 at this desired location can function as a resistance heater without a separate power resistor. Structurally similar, a heat-diffusing metal plane 153 and a long wound metal trace 156 functioning as a resistance heater are shown. Also, vias 154 are metal interconnect layers within the substrate that allow electrical connections from the detector or sensor 180 to the electrical connections on its bottom surface 167.

[0128] Here, we refer to examples that include EMC material molded around a sensor or detector, at least in part, as shown in Figures 10 to 20. For this purpose, Figures 10 to 11 include assembled and exploded views, respectively, of flow cells 1000 and 1100 having a fan-out region, which are formed, for example, by assembling a package containing EMC material molded around a sensor or detector onto a PCB substrate. Figures 12 to 13 show side views, respectively, of the package containing the EMC material and sensor or detector mounted on the flow cell 1000 and flow cell 1100. Figures 14 to 15 provide top and bottom views, respectively, of the flow cells 1000 and 1100 shown in Figures 10 to 11. Figures 10 to 15 are included to provide an overview of specific elements of the structure of various examples of flow cells 1000 and 1100 that can be formed using the methods described herein. Figures 16 to 19 illustrate these methods in more detail. Specifically, Figure 16 is a process flow 1600 showing the stepwise formation of the flow cell 1000 of Figure 10 (and Figure 14). Figure 17 is a workflow 1700 that repeats various aspects of Figure 16 but without an example of the flow cell 1000 itself. Figure 18 is a process flow 1800 showing the stepwise formation of the flow cell 1100 of Figure 11 (and Figure 15). Similar to Figure 17, Figure 19 is a workflow 1900 that reviews aspects of flow cell formation, including the flow cell 1100 of Figure 11 (and Figure 15), without an example of these aspects. Figure 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 Figure 10, this figure includes two diagrams of the flow cell 1000: an assembled diagram 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 into the EMC material 1082 is mounted on a PCB substrate 1050. In some examples, the detector or sensor 1080 is a CMOS image sensor having a patterned nanowell structure on its top surface (e.g., on the active surface). The PCB substrate 1050 may consist of 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 an internal heater (not shown). As is more apparent in exploded view 1035, the package 1081 is mounted on the PCB substrate 1050 using a film or adhesive. This attachment may or may not be formed by using a pick-and-place tool to place the package 1081 onto the film or adhesive 1040. In some examples, this adhesive is extruded and / or coated with a film that attaches the package 1081 to the substrate 1050. This film or adhesive 1040 may be thermocured and / or ultraviolet (UV) cured. A lid (e.g., glass) 1010 is attached using another film or adhesive 1020. This film or adhesive 1020 may be extruded or formed as a film to attach the lid 1010 to the package 1081. The space below the lid 1010 and above the active (top) surface of the detector or sensor (e.g., CMOS) 1080 and the upper surface (not covered with film or adhesive 1020) of the portion of EMC material 1082 molded around the detector or sensor (e.g., CMOS) 1080 forms a channel. The cover 1010 defines a fluid flow cell cavity having inlet and outlet fluid ports 1005. Contacts (not shown) on the active surface of a detector or sensor (e.g., CMOS) 1080 are wire-bonded 1070 to electrical connection points (e.g., bond pads, contact pads) 1060 on a PCB substrate 1050.In some examples, the electrical connection point 1060 is a metal bond pad located on the upper surface of the PCB substrate 1050, allowing wire bonding to a bond pad on the upper surface of the detector or sensor 1080 (e.g., a CMOS die).

[0130] As seen in Figure 11, and further illustrated in Figures 12-13, the difference between the flow cell 1000 in Figure 10 and the flow cell 1100 in Figure 11 is that in Figure 11, the EMC material 1182 is molded around the 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 will be discussed in more detail later herein, this layer 1183 is opened on the sensor or detector and / or active surface (e.g., using lithography or lithography plus lift-off process). In some examples, the planarized surface is a photoresist including, but not limited to, SU8. In some examples, as will be discussed later herein, the layer is patterned and then cured (e.g., fired). As shown in this example, the package 1181 containing the detector or sensor (e.g., CMOS) 1180 molded into the EMC material 1182 is mounted on a PCB substrate 1150. As shown in the example in Figure 10, in some examples the detector or sensor 1180 is a CMOS image sensor having a patterned nanowell structure on the top (e.g., on the active surface). The PCB substrate 1150 may consist of 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 an internal heater (not shown). As also shown in 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 using a pick-and-place tool. In some examples this adhesive is extruded and / or coated with a film that attaches the package 1181 to the substrate 1150. This film or adhesive 1140 may be thermocured and / or ultraviolet (UV) cured. A lid (e.g., glass) 1110 is attached using another film or adhesive 1120. In these examples, the glass lid 1110 is attached to a portion of the layer 1183. This film or adhesive 1120 may be extruded or formed as a film to attach the lid 1110 to the layer 1183.The space beneath the lid 1110 and the upper surface (not covered by the film or adhesive 1120) of the active (top) surface of the detector or sensor (e.g., CMOS) 1180 and the portion of the patterned layer 1183 molded on the EMC material 1182 around the detector or sensor (e.g., CMOS) 1180 forms a flow channel. The lid 1110 defines a fluid 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 wire-bonded 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 upper surface of the PCB substrate 1150, allowing wire bonding to bond pads on the upper surface of the detector or sensor 1180 (e.g., CMOS die).

[0131] Figure 12 is a side view of the flow cell assembly 1000 shown in Figure 10. Package 1081, which includes 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 upper surface of the EMC material 1072 not covered by the film or adhesive 1020 forms a 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 upper surface of the EMC material 1072 molded around the detector or sensor (e.g., CMOS) 1080 (not covered by the film or adhesive 1020) forms a flow path. The lid 1010 defines a fluid flow cell cavity having inlet and outlet fluid ports 1005. 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 a combination thereof), but it is understood that other conductive materials may be used. The vias 1087 are embedded in the EMC material 1082 at the bottom side 1086 of the sensor or detector 1080. As mentioned above, the example of the flow cell 1000 shown in Figure 10 may or may not include these vias 1087. In addition, as shown in Figures 21 to 31, these vias 1087 can be embedded in various configurations when embedded in the EMC material 1082. The configurations in this example are provided for illustrative purposes only and do not imply any limitations on these configurations.

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

[0133] Figure 14 shows a top view 1045 and a bottom view 1055 of the flow cell 1000. The flow cell 1000 is also shown in Figure 10, and an embodiment of the flow cell 1000 is shown in Figure 12. Returning to Figure 14, the bottom view 1055 of the flow cell 1000, specifically the substrate 1050, shows electrical contacts 1067 that may include pads containing pogo pins (called pogo pads). These electrical contacts 1067 enable electrical connection of the flow cell 1000 (specifically, ultimately to the detector or sensor 1080) to a receiving socket and / or fixture. As shown in later figures, vias and / or various other conductive elements formed across the PCB substrate 1050 connect electrical contacts 1060 to electrical contacts 1067. As previously mentioned, 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 the 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 view in Figure 14, is a fan-out region formed from a portion of the EMC material 1082 into which the detector or sensor 1080 is molded, as shown in Figure 10. The portion of the EMC material 1082 is not covered by the lid 1010, but rather extends along the longitudinal axis beyond the boundary of the lid 1010 in this case. The fan-out region formed from the portion of the EMC material 1082 into which the detector or sensor 1080 is molded is not visible from any view in Figure 14 because they are beneath the lid 1010.

[0134] Referring to Figure 15, which shows a top view 1145 and a bottom view 1155 of the flow cell 1100, the same flow cell 1100 is also shown in Figure 11. The bottom view 1155 of the flow cell 1100, specifically the substrate, shows electrical contacts 1167 that may include pads containing pogo pins (called pogo pads). These electrical contacts 1167 enable electrical connection of the flow cell 1100 (specifically, the detector or sensor 1180) to the receiving socket and / or fixture. As shown in later figures, vias and / or various other conductive elements formed across the PCB substrate 1150 connect electrical contacts 1160 to 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 the 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. Part of the EMC material 1182 is not covered by the lid 1110, but rather extends along the longitudinal axis beyond the boundary of the lid 1110 in this case. The patterned layer 1183 on top of the EMC material 1182 also extends along the longitudinal axis beyond the boundary of the lid 1110. Fan-out regions formed from part of the layer 1183 are not visible from any view in Figure 15 because they are beneath the lid 1110.

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

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

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

[0138] Figure 18 shows a workflow 1800 illustrating exemplary embodiments in the formation of several examples of flow cells, including but not limited to the flow cell 1100 shown in Figures 11 and 13. Unlike the flow cell 1000 in Figures 10 and 12, the flow cell 1100 in Figures 11, 13, and 15 includes a layer 1183 deposited on the front side of a sensor or detector 1180 and an EMC mold material 1182 for planarizing 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. Non-limiting examples of such planarized surfaces may be photoresists such as SU8. After patterning layer 1183, in some examples, layer 1183 may or may not be hardened by firing.

[0139] The reference numbers used in workflow 1800 refer to various embodiments of flow cell 1100 for illustrative purposes and do not introduce any limitations. In Figure 18, for example, a substrate 1150 is fabricated having electrical contacts such as pogo pads at the bottom (e.g., Figures 15, 1167) and electrical contacts 1160 (e.g., wire bond pads) at the top (1805). In some examples, the substrate includes an integrated heater assembly (not shown in Figure 18). The electrical contacts at the bottom (e.g., Figures 15, 1167) and the electrical contacts at the top 1160 are connected to each other via the substrate 1150 by connectors, including but not limited to vias. As previously stated, 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., Figure 11, 1140) is extruded and / or coated onto 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 (to allow the electrical contacts 1160 to be wire-bonded or otherwise connected to the electrical contacts of the sensor or detector 1180). The package 1181, which includes the sensor or detector 1180 molded from EMC material 1182, is planarized on top with a patternable resist including but not limited to SU8 (forming layer 1183) and oriented over the adhesive and / or film 1140 between the electrical contacts 1160 (1825). The planarized package 1181 (forming layer 1183) may be oriented, for example, using a pick-and-place machine. The electrical contacts 1160 are then wire-bonded to the electrical contacts (not shown) on the detector or sensor 1180 (e.g., a CMOS die) (1835). For example, the wire 1170 may be coupled to electrical contacts 1160 (e.g., wire bond pads) (these electrical contacts are not shown) on the substrate 1150 and on the detector or sensor 1180 (e.g., CMOS die) to form an electrical connection between them. After the electrical contacts are connected to each other using the wire 1170, an adhesive (e.g., epoxy) 1120 is extruded (e.g., in the form of a film) into a portion of the layer around the periphery of the sensor or detector 1180 (1845).The lid 1110 is attached to the adhesive and / or film 1120 (1865). The space beneath the lid 1110 and above the active (top) surface and portion of the upper surface of the layer 1183 of the detector or sensor (e.g., CMOS) 1180 (not covered by the film or adhesive 1120 but covered by the lid 1110) forms a flow path. The lid 1110 also defines a fluid flow cell cavity having inlet and outlet fluid ports 1105. The fluid ports 1105 are inlet and outlet openings within the lid 1110. The adhesive and / or film 1120 is cured.

[0140] Figure 19 shows a workflow 1900 that is similar to that of Figure 18. Referring to Figure 19, a package containing a sensor or detector is formed by molding 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 on 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 process. A non-limiting example of such a planarized surface may be a photoresist such as SU8. After patterning the layer, in some examples the layer may or may not be cured by firing. A substrate is fabricated having electrical contacts on the bottom surface and electrical contacts on the top surface (these are connected through the substrate using vias or other such connections) (1905). Adhesives and / or films are applied to the substrate (1915). A package containing a detector or sensor (e.g., a CMOS die) molded from EMC material is planarized with a patternable resist layer and oriented onto adhesive and / or film between electrical contacts that are not covered by adhesive and / or film (1925). The electrical contacts are wire-bonded to the electrical contacts on the detector or sensor (1935). In some examples, adhesive (e.g., epoxy) is dispensed into a cavity surrounding the detector or sensor to encapsulate the bond wires. Another adhesive and / or film is dispensed or coated onto a portion of the layer around the periphery of the detector or sensor (1945). A lid is attached to the adhesive and / or film, defining a fluid flow cell cavity with inlet and outlet fluid ports (1955). Both the first and second adhesives and / or films are cured at some point after they have been coated and utilized to form the attachment.

[0141] Referring here to Figure 20, as previously stated, some examples of flow cells formed using some aspects of the method described herein are formed on a substrate containing various heating elements. Similar to Figure 9, Figure 20 shows a flow cell 1000 in a side view similar to the flow cell 1000 of Figures 10 and 12, with this detail added to the substrate 1050. Numbering consistency is provided for illustrative purposes. The flow cells 1100 of Figures 11 and 13 may share substantially the same elements that preserve a patterned layer (e.g., Figure 13, 1183) on top of an EMC material (e.g., Figure 13, 1182). Although Figure 20 does not overlap with the reference numbers for the flow cells of Figures 11 and 13, the generally named elements are relevant to both configurations.

[0142] As also shown in Figures 12 and 13, in Figure 20, EMC material 1082 is formed around a sensor or detector 1080 (e.g., a CMOS die) into which vias 1087 of a conductive material such as a metallic material (e.g., Cu (copper), Au (gold), W (tungsten), Al (aluminum), or a combination thereof) are embedded. Examples of the structure and formation of the EMC material 1082 embedded in the vias 1087 are discussed further with reference to Figures 21 to 32.

[0143] Returning to Figure 20, the flow cell 1000 in Figure 20 includes various additional embodiments, which can also be seen in other figures. For example, the flow cell 1000 includes a package 1081 containing an EMC material 1082 molded around a sensor or detector 1080 to provide fluid fan-out for use across the active surface of the flow cell 1000. In this example, the detector or sensor 1080 is a CMOS image sensor having a patterned nanowell structure 1077 on top. The package 1081 is attached to a substrate with an adhesive and / or film 1040. This adhesive and / or film 1040 may be extruded or coated as a film to fabricate this attachment and then cured (e.g., thermosetting or UV curing) or not. The substrate 1050 in this example can 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 on its bottom surface 1067. In this example, the electrical connections on the top surface 1060 are bond pads (e.g., metal) that allow wire bonding to the bond pads on the top surface of the detector or sensor 1080 (e.g., CMOS die). On the other hand, the electrical connections on its bottom surface 1067 are pogo pads that allow electrical connections to a receiving socket or fixture. The flow cell 1000 contains a fluid, and the glass lid 1010 defines a fluid flow cell cavity having inlet and outlet fluid ports 1005. The lid 1010 (e.g., glass) is attached to the support piece 1060 and part of the detector or sensor 1080 with adhesive 1020. Like the adhesive and / or film 1040, this adhesive or film 1020 may also be dispensed or coated as a film and then cured (e.g., thermosetting or UV curing) or not.

[0144] The substrate 1050 in Figure 20 has an embedded heater for controlling the package temperature. As previously mentioned, some or all of these elements can also be integrated into the flow cell 1100 example in Figures 11 and 13. In the flow cell 1000 of Figure 20, heating can be achieved by one or more of two methods. Firstly, a power resistor 1052 may be located on the top or bottom of the substrate 1050, and heat is transferred to a desired location by via 1059, and a metal plane 1053 spreads the heat over a desired area to maintain a uniform temperature. Secondly, a long wound metal trace 1056 at this desired location can function as a resistance heater without a separate power resistor. Structurally similar, a heat-diffusing metal plane 1053 and a long wound metal trace 1056 functioning as a resistance heater are shown. Also, via 1054 is a metal interconnect layer within the substrate that allows electrical connection from the detector or sensor 1080 to an electrical connection on its bottom surface 1067.

[0145] In the examples of flow cells 1000, 1100 in Figures 10 and 11, the flow cells 1000, 1100 include packages 1081, 1181 which themselves contain EMC material 1082, 1182 molded around sensors or detectors 1080, 1180.

[0146] Figures 21–32 illustrate various examples of methods for forming a package that includes one or more die portions and one or more pillars or vias of a conductive material (e.g., 2181, Figure 29) surrounded by a cured molded material (e.g., EMC material). For consistency, as with the previous figures, the same designer is used in these figures for common and / or similar elements wherever possible. In the formed package, the die (e.g., sensor or detector) is at least partially embedded in the molded material, so as to be a pillar. Thus, these packages include embodiments of packages 1081 and 1181 of flow cells 1000 and 1100. As previously stated, in some examples of flow cells discussed herein, packages 1081 and 1181 may be substantially the same as or somewhat similar to the packages shown in Figures 21A–21K. However, unlike the previous figures which focused on or showed the formation of flow cells that may or may not include this type of package, Figures 21–32 focus on the details of examples relating to forming the package itself. Figures 21 to 31 show examples of various elements in the overall flow cell formation process using packages, as well as an example of a completed flow cell. Figure 33, however, reviews some of the elements of the examples shown in Figures 21 to 31 for clarity, but does not provide any examples.

[0147] Referring first to Figures 21-23, in these non-limiting examples, the package is formed on a carrier (e.g., a glass carrier) by using a temporary adhesive 2112 to attach elements such as pillars 2114 and dies (e.g., sensors or detectors) 2113 to the carrier 2111 (e.g., ceramic or glass). Figure 21 shows the carrier 2111 and the temporary adhesive 2112 (e.g., film or adhesive) being dispensed onto the carrier 2111. The adhesive 2112 is temporary, as its removal (including the removal of the carrier 2111) is also part of this example and will be discussed later. 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 surface of the sensor or detector 2180 is labeled in Figures 23-31, and may or may not be valid as a sensor or detector 2180 until it undergoes the chemical treatment discussed and illustrated in Figure 29. However, referring specifically to Figures 22-23, one or more pillars 2114 and one or more dies 2113 are oriented on the carrier 2111 and on the temporary adhesive 2112. In some examples, these elements may be oriented using a pick-and-place procedure.

[0148] In the examples shown in Figures 21 to 31, the orientation of the vias (e.g., pillars 2114) and dies 2113 is such that each die 2113 is between two pillars 2114. This orientation is provided merely as an example. The pillars 2113 provide electrical connections from each of the sensors or detectors 2180 to any element below the package, including the substrate. While this particular orientation demonstrates this advantage, those skilled in the art will understand that various different orientations can be used to provide similar or the same functionality. As previously mentioned in Figures 12 and 13, vias 1087, 1187 can be oriented below the sensors or detectors 1080, 1180. Since the vias 1087, 1187 in Figures 21 to 31 show a particular configuration of conductive elements different from some of the orientations discussed above, these conductive elements are referred to as pillars 2114 for clarity.

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

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

[0151] Figure 26 shows that the top surface of pillar 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 pillar 2114 to an additional via 2118 (e.g., Figure 27). In some examples, the 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 pillar 2114 and ultimately to the sensor or detector 2180. Figures 27–31 do not show the seed layer 2117 because it is not implemented or is not visible even if implemented.

[0152] In Figure 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 RDL 2121) is patterned, a portion of the RDL is opened to provide access to electrical elements. One non-limiting example of a process that may be used to form the opening 2122 is photolithography. A conductive material 2118 (e.g., copper) is spread through the opening 2122 so that the material is electrically coupled to one or more of the pillars 2114. The material within the opening 2122 forms vias to the pillars 2114. Various non-limiting examples include one to three RDLs. The opening 2122 of the upper RDL is plated (e.g., with gold and / or copper) to form electrical contacts 2119.

[0153] Referring to Figures 28 and 29, as shown in Figure 28, once the electrical contact 2119 is formed, the structure (as before) is rotated 180 degrees, the temporary adhesive 2112 is disengaged, and both the temporary adhesive 2112 and the carrier 2111 can be removed from the structure. Figure 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 containing what will become the active surface 2123 (see Figure 29). Figure 29 shows an example of at least one package 2181. As shown in Figure 29, the chemical 2124 is applied to the surface of each die 2113, allowing 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 part of the active surface 2123 in several flow cells.

[0154] As discussed herein, pillar 2114 provides connectivity to the sensor or detector 2180 via the package, and therefore Figure 30 shows two different non-limiting examples of the type of connection that can be formed between the electrical contact 2119 and the sensor or detector 2180. On the left side of Figure 20, an electrical contact 2126 is wire-bonded to the sensor or detector 2180. On the right side, printing is used to form a printed connection 2127 between the sensor or detector 2180 and the electrical contact 2119. In Figure 31, a lid 2110 is added on each active surface 2123, defining fluid channels 2128 above the active surfaces 2123 and below the lid 2110. In some examples, adhesive is used to secure the lid 2110 to the top surface of the package 2181.

[0155] Figure 32 shows a workflow 3200 reviewing an embodiment of the formation of the flow cell 2100. Workflow 3200 illustrates an embodiment of assembling a package containing a cured molding material surrounding one or more die portions. 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 the surface of the carrier (e.g., glass, ceramic, etc.) (3205). One or more pillars and one or more dies are oriented onto the adhesive (e.g., using pick and place) (3215). In some examples, the pillars have a vertical length greater than that of the dies. Material (e.g., EMC material) is molded around the top surface of the carrier and the surfaces of one or more dies and one or more pillars, and the mold is cured (3225), such that the top surface of the mold has a vertical length greater than that of the pillars. The surface of the cured molding material is ground to create a new surface, exposing the top surfaces of one or more pillars and one or more dies (3235). The top surface of the pillars is plated with a conductive material to create a seed layer for conductive vias (3245). To form these vias, one or more redistribution layers are applied, the application including patterning each layer onto a new surface, opening portions of the layers to form openings, spreading the conductive material through each opening so that the conductive material spreads through the openings, and forming vias on 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). Here, since the package is formed, in some examples a chemical is applied to the package surface on the exposed die surface, and the exposed pillar surface is plated to form electrical contacts (3275). The electrical contacts are electrically coupled to portions of the die surface that have been treated or will be treated with the chemical (3297). The lid is attached to the package in an orientation that defines fluid channels on the die surface that has been treated or will be treated with the chemical (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 upper surface of which includes electrical contacts. The method may include oriented a package on the first adhesive, the package including a die, the upper surface of which includes an active surface and electrical contact points, and at least two surfaces adjacent to the active surface on opposite sides of the active surface forming a fan-out region for use in the fluid path of the flow cell. The method may include connecting electrical contacts on the upper surface of the substrate to electrical contact points 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. Attachment defines a fluid flow cell cavity beneath the lid and on the surface including the active surface and fan-out region.

[0157] In some examples, the method may include forming a package, and forming the package may include oriented the die onto a first adhesive. The method may also include forming a fan-out region by oriented one or more support pieces onto the first adhesive adjacent to at least two sides of the die, wherein the fan-out region includes a portion of the upper surface of the support pieces.

[0158] In some examples, the arrangement of one or more support pieces includes two support pieces, and the orientation of one or more support pieces on the first adhesive adjacent to at least two sides of the die includes arranging two support pieces adjacent to the die on both sides of the die.

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

[0160] In some examples, the package includes a hardened electroformed compound (EMC) material molded around a portion of the die, with a portion of the EMC material containing a fan-out region.

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

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

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

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

[0165] In some examples of methods for forming flow cells, forming a package further includes planarizing the surface of the EMC material adjacent to the active surface.

[0166] In some examples of methods for forming a flow cell, planarization includes depositing a layer on a surface including the top surface of the die and the EMC material surface adjacent to 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 layers include a photoresist.

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

[0169] In some examples of methods for forming a flow cell, the process of forming the package further involves embedding vias into the EMC material before curing the EMC material around the die portion.

[0170] In some examples of methods for forming flow cells, vias are made of conductive material.

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

[0172] In some examples of methods for forming flow cells, vias extend from the die surface opposite the active surface through the EMC material in the direction opposite to the active surface.

[0173] In some examples of methods for forming a flow cell, connecting electrical contacts on the upper surface of a substrate to electrical contact points on a die involves wire bonding the electrical contacts to the electrical contact points.

[0174] In some examples of methods for forming flow cells, the method involves encasing wire-bonded connections in epoxy.

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

[0176] In some examples of methods for forming flow cells, 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 includes a material selected from the group consisting of glass-reinforced epoxy laminate material, FR4, and co-fired ceramic sheet.

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

[0180] In some examples of methods for forming a flow cell, the method includes forming a heating element within a substrate.

[0181] In some examples of methods for forming a flow cell, forming a heating element involves placing one or more resistors on one or more of the top and bottom surfaces of a substrate, and coupling one or more resistors to a metal plane in the substrate via vias.

[0182] In some examples of methods for forming a flow cell, the heating element includes a long wound metal trace and is formed within the substrate so that it functions as a resistance heater.

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

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

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

[0186] In some examples of methods for forming flow cells, the active surface of the die contains nanowells.

[0187] In some examples of flow cells disclosed herein, the flow cell may include a substrate having electrical contacts on its upper surface. The electrical contacts on the upper surface of the substrate are connected to electrical contact points on the upper surface of the die. The flow cell may also include a first curing adhesive, which is bonded to a package. The package may include a die, the upper surface of which further includes an active surface, and a fan-out region, the fan-out region including surfaces adjacent to at least two opposite sides of the active surface, which at least partially defines the fluid path of the flow cell. The flow cell may also include a second curing adhesive, the second curing adhesive bonding a portion of the upper surface of the package to a lid, defining a fluid flow cell cavity beneath 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 flow cells, the package comprises one or more support pieces adjacent to at least two opposite sides of the active surface of the die, wherein one or more support pieces further comprises one or more support pieces that include a fan-out region.

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

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

[0191] In some examples of flow cells, the package further comprises a cured electroformed compound (EMC) material molded around a portion of the die, and a portion of the EMC material forming an EMC material surface adjacent to at least two opposite sides of the active surface, wherein the portion of the EMC material surface includes a fan-out region.

[0192] In some examples of flow cells, the package includes a hardened electroformed compound (EMC) material molded around a portion of the die, and a layer deposited on the surface of the EMC material adjacent to the active surface on at least two opposite sides of the active surface, wherein the fan-out region includes a portion of the layer.

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

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

[0195] In some examples of flow cells, the substrate further includes electrical contacts on the bottom surface of the substrate, and these electrical contacts on the bottom surface of the substrate are electrically coupled to electrical contacts on the top surface of the substrate by vias formed through the substrate.

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

[0197] In some examples of flow cells, the heating element includes one or more resistors on one or more of the top and bottom surfaces of the substrate, a metal plane within the substrate, and vias through the substrate connecting one or more resistors within the substrate to the metal plane.

[0198] In some examples of flow cells, the heating element includes a long wound metal trace within the substrate so that it functions as a resistance heater.

[0199] In some examples of flow cells, the lid includes two openings, each defining either an inlet fluid port or an outlet fluid port.

[0200] In some examples of flow cells, 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 flow cells, the substrate includes a material selected from the group consisting of glass-reinforced epoxy laminate material, FR4, and co-fired ceramic sheet.

[0203] In some examples of flow cells, 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, wherein the upper surface of the substrate includes electrical contacts. The method may also include oriented a die onto the first adhesive, wherein the upper surface of the die includes an active surface and electrical contact points. The method may also include forming a fan-out region for use in the fluid path of a flow cell, wherein forming the fan-out region may include oriented one or more support pieces onto the first adhesive adjacent to at least two sides of the die, wherein portions of the upper surfaces of the support pieces on at least two sides of the die include the fan-out region. The method may further include connecting electrical contacts on the upper surface of the substrate to electrical contact points on the die. The method may include applying a second adhesive to portions of one or more support pieces. The method may also include attaching a lid to the second adhesive, wherein attaching defines a fluid flow cell cavity beneath the lid and on the surface including the active surface and the fan-out region.

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

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

[0207] In some examples of the methods disclosed herein, the method also includes fixing wire-bonded connections with epoxy.

[0208] In some examples of the methods disclosed herein, forming a heating element involves mounting long wound metal traces within a substrate so that they function as a resistance heater.

[0209] In some examples of the methods disclosed herein, the method also includes heating the substrate using a heating element.

[0210] Some examples of flow cells disclosed herein include: a substrate having electrical contacts on its upper surface, wherein the electrical contacts on the upper surface of the substrate are connected to electrical contact points on the upper surface of a die; a first curing adhesive, the first curing adhesive bonding the die and one or more support pieces adjacent to at least two sides of the die to the substrate, such that a portion of the upper surface of the die and a portion of the upper surface of one or more support pieces form a surface utilized in the fluid path of the flow cell; a second curing adhesive, the second curing adhesive bonding an area of ​​one or more support pieces and an area of ​​the upper surface of the die adjacent to the surface utilized in the fluid path of the flow cell to a lid; and a lid, the lid defining a fluid 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, one or more support pieces include two support pieces oriented on both sides of the die.

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

[0213] In some examples of the methods disclosed herein, a method for forming a flow cell includes applying a first adhesive to a substrate, the upper surface of which includes electrical contacts. The method may also include oriented a die onto the first adhesive, the upper surface of which includes an active surface and electrical contact points. The method may also include forming a fan-out region for use in the fluid path of the flow cell, the formation of which may include oriented two support pieces onto the first adhesive on both sides of the die, each of the two support pieces adjacent to the die, the upper surface of the die and the upper surfaces of the two support pieces forming an upper surface, and discharging material to fill the gap between the two support pieces and the die. The method may also include connecting electrical contacts on the upper surface of the substrate to 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, thereby defining a fluid flow cell cavity beneath and above the lid.

[0214] In some examples of the methods disclosed herein, a method for forming a flow cell comprises applying a first adhesive to a substrate, wherein the upper surface of the substrate includes electrical contacts. The method may also include oriented a die onto the first adhesive, wherein the upper surface of the die includes an active surface and electrical contacts. The method may also include forming a fan-out region for use in the fluid path of the flow cell, wherein forming the fan-out region comprises oriented a support piece onto the first adhesive, wherein the support piece includes a notch, and the orientation comprises positioning the support piece on the first adhesive such that the die and electrical contacts are positioned within the notch, wherein the fan-out region comprises portions of the upper surface of the support piece on both sides of the die, wherein the portions of the upper surface and the active surface form the upper surface. The method also includes connecting the electrical contacts on the upper surface of the substrate to the electrical contacts on the die with bond wires. The method also includes discharging a second adhesive into a notch such that the second adhesive fills the space in the notch between the die and the support piece and encapsulates the bond wires. 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 the lid to the third adhesive, thereby defining a fluid flow cell cavity beneath and above the lid.

[0215] In some examples of the methods disclosed herein, a method for forming a flow cell comprises applying a first adhesive to a substrate, wherein the upper surface of the substrate includes electrical contacts. The method may also include oriented a package comprising a cured electroformed compound (EMC) material molded around a portion of a die, wherein the upper surface of the die includes an active surface and electrical contact points, and a portion of the EMC material forms EMC material surfaces adjacent to at least two opposite sides of the active surface. The method may also include connecting electrical contacts on the upper surface of the substrate to electrical contact points on the die. The method may also include applying a second adhesive to a portion of the upper surface of the package and attaching a lid to the second adhesive, wherein the attachment defines a fluid flow cell cavity beneath the lid and on a surface including an active surface and a fan-out region for use in the fluid path of the flow cell, wherein the fan-out region includes another portion of the upper surface of the package.

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

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

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

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

[0220] In some examples of the methods disclosed herein, the substrate further includes electrical contacts on the bottom surface of the substrate, and the electrical contacts on the bottom surface of the substrate are electrically coupled to 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 vias embedded in EMC material.

[0222] Some examples of flow cells disclosed herein include a substrate having electrical contacts on its upper surface, wherein the electrical contacts on the upper surface of the substrate are connected to electrical contact points on the upper surface of the die. The flow cell may also include a first curing adhesive, the first curing adhesive bonding a package comprising a cured electroformed compound (EMC) material molded around a portion of the die, the upper surface of the die being exposed and including an active surface and electrical contact points, a portion of the EMC material forming EMC material surfaces adjacent to the active surface on at least two opposite sides of the active surface, and a portion of the EMC material surfaces including a fan-out region for use in the fluid path. The flow cell may also include a second curing adhesive, the second curing adhesive bonding a portion of the upper surface of the package to a lid, defining a fluid flow cell cavity beneath the lid and above the surface including the active surface and fan-out region. The flow cell may also include a lid.

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

[0224] In some examples of 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 flow cells disclosed herein, the substrate further includes electrical contacts on the bottom surface of the substrate, which are electrically coupled to 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 having electrical contacts on its upper surface, wherein the electrical contacts on the upper surface of the substrate are connected to electrical contact points on the upper surface of the die. The flow cell may include a first curing adhesive, the first curing adhesive bonding a package comprising a cured electroformed compound (EMC) material molded around a portion of the die, the upper surface of the die being exposed and including an active surface and electrical contact points, a portion of the EMC material forming EMC material surfaces adjacent to the active surface on at least two opposite sides of the active surface, a layer planarizing the EMC material surfaces, the portion of the EMC material surfaces planarized by the layer including a fan-out region for use in a fluid path. The flow cell may include a second curing adhesive, the second curing adhesive bonding a portion of the upper surface of the package to a lid, defining a fluid flow cell cavity beneath the lid and above the surface including the active surface and 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 comprising a cured molding material surrounding one or more die portions, wherein one or more pillars of a first conductive material are embedded in the molding material, and the assembly includes applying a temporary adhesive to the surface of a carrier. The method may also include orienting one or more pillars on the adhesive. The method may also include orienting one or more dies on the adhesive such that one or more pillars are oriented between each of the one or more dies, wherein each one or more pillar has a vertical length greater than each of the one or more dies. The method may also include molding the material around the top surface of the carrier and the surfaces of one or more dies and one or more pillars such that the top surface of the mold has a vertical length greater than one or more pillars, wherein the top surface of the mold is parallel to the surface of the carrier. The method may also include curing the molding material. The method may also include grinding the top surface of the mold to expose the top surfaces of one or more pillars and one or more dies to create new surfaces. The method may also include plating the top surface of 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 each RDL application may include patterning a layer on a new surface. The method may also include opening portions of the layer to form openings. The method may also include spreading a third conductive material into each opening so that the third conductive material spreads through the openings and electrically couples to the seed layer. The method may also include attaching electrical contacts to portions of the third conductive material within the openings of one or more RDLs. The method may also include removing the carrier and temporary adhesive to expose the package surface.

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

[0229] In some examples of the methods disclosed herein, the method involves electrically coupling electrical contacts on a pillar to a portion of the surface of one or more dies containing a chemical substance.

[0230] In some examples of the methods disclosed herein, the method for electrically coupling electrical contacts on a pillar to a portion of the surface of one or more dies containing a chemical substance is selected from the group consisting of wire bonding and printing.

[0231] In some examples of the methods disclosed herein, the method comprises attaching one or more lids to the package surface, wherein the fluid flow cell cavity is defined under each of the one or more lids and on the surface of each of the corresponding one or more sensors, which 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 comprises one or more of nickel and gold.

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

[0235] In some examples of the methods disclosed herein, opening up a portion of a layer to form an opening involves utilizing photolithography.

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

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

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

[0239] In some examples of flow cells disclosed herein, the flow cell includes a package comprising a cured material molded around a portion of a die, wherein one or more pillars of a first conductive material are embedded in the molded material, and the top surface of the package includes the active surface of the die. The flow cell may also include a lid attached to a portion of the top surface of the package, wherein a fluid flow cell cavity is defined beneath 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 the bottom surface of the package. The RDLs include openings filled with a conductive material that are electrically coupled to at least one of one or more pillars.

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

[0242] In some examples of flow cells disclosed herein, the curing material comprises an electroforming compound (EMC).

[0243] The flowcharts and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of the system, method, and computer program product in various examples of this implementation. In this regard, each block in the flowchart or block diagram represents a module, segment, or part of an instruction, which contains one or more executable instructions for implementing a specified logical function. In some alternative implementations, the functions shown in the blocks may occur in a different order than shown in the figure. For example, two consecutively shown blocks may actually be executed substantially simultaneously, or blocks may be executed in reverse order, depending on the functions involved. It should also be noted that each block in the block diagram and / or flowchart, and combinations of blocks in the block diagram and / or flowchart, may be implemented by a dedicated hardware-based system that performs a particular function or operation, or by a combination of dedicated hardware and computer instructions.

[0244] The terms used herein are intended to illustrate only specific examples and are not intended to be limiting. When used herein, the singular forms “a,” “an,” and “the” are intended to include the plural form unless otherwise explicitly indicated by the context. It will be further understood that, when used herein, the terms “comprises” and / or “comprising” identify the presence of a described feature, integer, step, process, action, element, and / or component, but do not exclude the presence or addition of one or more other features, integers, steps, processes, actions, elements, components, and / or groups thereof.

[0245] Where applicable, in addition to the functional elements of the claims below, all corresponding structures, materials, actions, and equivalents of all means or steps are intended to include any structures, materials, or actions for performing the function in combination with other claimed elements specifically claimed. While one or more examples have been presented for illustrative and explanatory purposes, they are not intended to be exhaustive or limit to the forms disclosed. Numerous modifications and changes will be apparent to those skilled in the art. The examples have been selected and described to best illustrate various aspects and practical applications, and to enable others skilled in the art to understand the various examples with various modifications suitable for specific uses conceivable.

[0246] It should be understood that all combinations of the aforementioned concepts and further concepts discussed in more detail below (where such concepts are not mutually contradictory) are conceived to be part of the subject matter of the invention disclosed herein, at least in order to achieve the advantages described herein. Specifically, all combinations of the subject matter of the claims appearing at the end of this disclosure are conceived to be part of the subject matter disclosed herein. It should also be understood that terms used expressly herein and that may appear in any disclosure incorporated by reference should be given meanings that are most consistent with the specific concepts disclosed herein.

[0247] This written description, using examples, discloses the subject matter and enables any person skilled in the art to practice the subject matter, including by fabricating and using any device or system and by performing any incorporated method. The patentable scope of the subject matter is defined by the claims and may include other examples that a person skilled in the art could conceive. Such other examples are intended to be within the claims if they include structural elements that are no different from the literal words of the claims, or if they include equivalent structural elements that differ only slightly from the literal words of the claims.

[0248] It should be understood that the above description is illustrative and not restrictive. For example, the examples (and / or embodiments thereof) described above can be used in combination with one another. In addition, many modifications can be made to adapt specific situations or materials to the teachings of the various examples without departing from their scope. The dimensions and types of materials described herein are intended to define the parameters of the various examples, but they are provided merely as examples and are not restrictive in any way. A number of other examples will become apparent to those skilled in the art upon consideration of the above description. Thus, the scope of the various examples should be determined by referring to the appended claims, along with the entire scope of equivalents to which such claims are entitled. In the appended claims, the terms “including” and “in which” are used as plain English equivalents to “comprising” and “wherein,” respectively. Furthermore, in the following claims, terms such as “first,” “second,” and “third” are used merely as labels and are not intended to impose numerical requirements on those objects. The term “based on” in this specification encompasses relationships where the elements are partially based, as well as relationships where the elements are fully based. The term “defined” encompasses relationships where the elements are partially defined, as well as relationships where the elements are fully defined. Furthermore, the following limitation of claims is not written in means-plus-function form, and such limitation of claims is not intended to be interpreted under 35 U.S.SC § 112, paragraph 6 unless it explicitly uses the phrase “means for,” followed by a description of a function without further structure. It should be understood that not all such objectives or benefits described above can necessarily be achieved according to specific embodiments of the present invention.Therefore, for example, a person skilled in the art will recognize that the systems and techniques described herein can be embodied or implemented in a manner that achieves or optimizes one or a group of advantages taught herein, even if they do not necessarily achieve other purposes 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 that are not described but are appropriate to the spirit and scope of the subject matter. Additionally, although various examples of the subject matter have been described, it should be understood that the aspects of this disclosure may include only some of the examples described. Furthermore, although some examples have been described as having a certain number of elements, it will be understood that the subject matter can be practiced with fewer or more elements than that certain number. Therefore, the subject matter should not be considered limited by the above description, but only by the appended claims.

Claims

1. A method for forming a flow cell, The first adhesive is applied to the substrate, wherein the upper surface of the substrate includes electrical contacts. Placing a package on the first adhesive, wherein the package includes a die, the upper surface of the die includes an active surface and electrical contact points, and at least two opposite sides of the horizontal boundary of the active surface, adjacent to the active surface, form a fan-out region for use in the fluid path of the flow cell. Connecting the electrical contacts on the upper surface of the substrate to the electrical contact points on the die, Applying a second adhesive to a portion of the aforementioned package, Attaching the lid to the second adhesive, wherein the attachment defines a fluid flow cell cavity beneath the lid and on the surface including the active surface and the fan-out region, The process further includes forming the package, and forming the package is The die is placed on the first adhesive, A method for forming the fan-out region by arranging one or more support pieces on the first adhesive adjacent to at least two opposite sides of the horizontal boundary of the die, wherein the fan-out region includes a portion of the upper surface of the support pieces.

2. The method according to claim 1, wherein the one or more support pieces include two support pieces, and the arrangement of the one or more support pieces on the first adhesive adjacent to at least two sides of the horizontal boundary of the die includes arranging two support pieces adjacent to the die on both sides of the die.

3. The method according to claim 1, wherein the one or more support pieces include one support piece, the one support piece includes a notch, and the arrangement of the one or more support pieces on the first adhesive adjacent to the at least two sides of the horizontal boundary of the die includes arranging the one support piece such that the die and electrical contacts are located within the notch.

4. The method according to claim 1, wherein the package comprises a hardened electroformed compound (EMC) material molded around the portion of the die, and a portion of the EMC material comprises the fan-out region.

5. It is a flow cell, A substrate having electrical contacts on its upper surface, wherein the electrical contacts on the upper surface of the substrate are connected to electrical contact points on the upper surface of a die, A first curing adhesive, wherein the first curing adhesive is bonded to a package, and the package is The die, wherein the upper surface of the die further includes an active surface, A first curing adhesive comprising a fan-out region including surfaces adjacent to at least two opposite sides of the horizontal boundary of the active surface, wherein the fan-out region at least partially defines the fluid path of the flow cell, A second curing adhesive, wherein a portion of the upper surface of the package is bonded to the lid, defining a fluid flow cell cavity beneath the lid and on the surface including the active surface and the fan-out region, The lid, including, The aforementioned package, A flow cell comprising one or more support pieces adjacent to at least two opposite sides of the horizontal boundary of the active surface of the die, wherein the one or more support pieces further comprise one or more support pieces that include the fan-out region.

6. The flow cell according to claim 5, wherein the one or more support pieces include two support pieces positioned on at least two opposite sides of the horizontal boundary of the active surface of the die.

7. The flow cell according to claim 5, wherein the one or more support pieces include one support piece, the one support piece includes a notch, and the die and the electrical contacts on the upper surface of the substrate are arranged within the notch.

8. The aforementioned package, A hardened electroformed compound (EMC) material is formed around the portion of the die. The present invention further includes a portion of the EMC material that forms an EMC material surface adjacent to the active surface on at least two opposite sides of the horizontal boundary of the active surface, The flow cell according to claim 5, wherein a portion of the surface of the EMC material includes the fan-out region.

9. The aforementioned package, A hardened electroformed compound (EMC) material formed around the die portion, The flow cell according to claim 5, comprising a layer deposited on the EMC material surface adjacent to the active surface on at least two opposite sides of the horizontal boundary of the active surface, wherein the fan-out region includes a portion of the layer.

10. The flow cell according to claim 8 or 9, wherein the package further comprises vias embedded in the EMC material.

11. The flow cell according to any one of claims 5 to 10, wherein the substrate further includes an electrical contact on the bottom surface of the substrate, and the electrical contact on the bottom surface of the substrate is electrically coupled to the electrical contact on the top surface of the substrate by vias formed through the substrate.

12. The substrate further includes a heating element, The aforementioned heating element One or more resistors on one or more of the top surface and the bottom surface of the substrate, The metal plane within the substrate, A via passing through the substrate connects one or more resistors to the metal plane in the substrate, A flow cell according to claim 11, comprising:

13. The flow cell according to claim 12, wherein the heating element includes a long wound metal trace in the substrate so that it functions as a resistance heater.

14. The flow cell according to any one of claims 5 to 13, wherein the lid includes two openings, each opening defining one of either an inlet fluid port or an outlet fluid port.

15. The flow cell according to any one of claims 5 to 14, wherein the upper surface of the die includes a nanowell.

16. The flow cell according to any one of claims 5 to 15, wherein the substrate comprises a material selected from the group consisting of glass-reinforced epoxy laminate material, FR4, and co-fired ceramic sheet.

17. The flow cell according to any one of claims 5 to 16, wherein the die is a complementary metal oxide film semiconductor.

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