Gasket assemblies and related systems and methods
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- ILLUMINA INC
- Filing Date
- 2022-01-20
- Publication Date
- 2026-08-04
Smart Images
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Abstract
Description
Technical Field
[0001] Related Applications This application claims the benefits and priority of U.S. Provisional Patent Application No. 63 / 170,946, filed on April 5, 2021, and U.S. Provisional Patent Application No. 63 / 199,916, filed on February 2, 2021, the entire contents of each of which are hereby incorporated by reference for all purposes. Background Art
[0002] An array determination platform may include a fluid interface that can form a fluid connection with a flow cell.
Summary of the Invention
[0003] The advantages and benefits over the prior art described hereinafter in this disclosure can be achieved through the provision of a gasket assembly and related systems and methods. Various implementations of the apparatus and methods are described below, and apparatuses and methods that include and exclude the additional implementations listed below in any combination (on the premise that such combinations are not contradictory) can overcome these drawbacks and achieve the benefits described herein.
[0004] According to a first implementation, the apparatus includes a flow cell. The flow cell has one or more channels. Each channel has a first channel opening and a second channel opening. The first channel opening is positioned at a first end of the flow cell, and the second channel opening is positioned at a second end of the flow cell. A gasket assembly is coupled to each second channel opening. Each gasket assembly includes an adhesive stack and a gasket. The adhesive stack includes a first side joined to the gasket and a second side joined to the flow cell.
[0005] According to the second embodiment, the apparatus includes a gasket assembly including a gasket, and an adhesive stack including a first adhesive, a separator layer, and a second adhesive. The separator layer has a first side and a second side that are at least partially covered by the first adhesive. The second adhesive at least partially covers the second side of the separator layer. The separator layer is positioned between the first adhesive and the second adhesive. The gasket is bonded to the second adhesive. The second adhesive is positioned between the separator layer and the gasket. The apparatus also includes a release liner to which the first adhesive of the adhesive stack is peelably bonded.
[0006] According to the third implementation, the apparatus includes a system and a flow cell. The system includes a flow cell interface, and the flow cell has one or more channels. Each channel has a first channel opening and a second channel opening. The first channel opening is located at the first end of the flow cell, and the second channel opening is located at the second end of the flow cell. A gasket assembly is coupled to each second channel opening. Each gasket assembly includes an adhesive stack and a gasket. The adhesive stack includes a first side bonded to the gasket and a second side bonded to the flow cell. The flow cell interface is engageable with the corresponding gasket to establish a fluid coupling between the system and the flow cell.
[0007] According to the fourth implementation, the method includes picking up a gasket assembly using the head of a pick-and-place machine. The gasket assembly includes an adhesive stack and a gasket. The adhesive stack includes a first side bonded to the gasket and a second side. The method includes placing the second side of the gasket assembly on a surface surrounding the opening of a channel in a flow cell.
[0008] According to the fifth implementation form, the apparatus includes a flow cell including a channel with a channel opening, and a gasket assembly coupled to the channel opening. The gasket assembly includes an adhesive stack and a gasket. The adhesive stack includes a first side bonded to the gasket and a second side bonded to the flow cell.
[0009] According to the sixth implementation form, the device includes a gasket with adhesive on the back.
[0010] According to the seventh implementation form, the method includes picking up a gasket with adhesive backing and placing the gasket with adhesive backing on a flow cell. The method also includes pressing the gasket with adhesive backing onto the flow cell, thereby bonding the gasket with adhesive backing to the flow cell.
[0011] Furthermore, according to the first, second, third, fourth, fifth, sixth, and / or seventh implementations described above, the apparatus and / or method may further include or comprise one or more of the following:
[0012] In one implementation configuration, the adhesive stack has through holes, and the gasket has through holes that are aligned with the through holes of the adhesive stack to allow fluid communication through the gasket assembly.
[0013] In another implementation, the adhesive stack includes a first adhesive bonded to a flow cell and a second adhesive bonded to a gasket and positioned between the first adhesive and the gasket.
[0014] In another implementation configuration, each gasket assembly further includes a separator layer positioned between a first adhesive and a second adhesive. The first adhesive bonds both the flow cell and the separator layer, while the second adhesive bonds both the separator layer and the gasket.
[0015] In another implementation, the separation layer contains polyethylene terephthalate.
[0016] In another implementation, the separation layer includes through holes, and the gasket has through holes aligned with the through holes in the separation layer. The first adhesive coats the first side of the separation layer, and the second adhesive coats the second side of the separation layer.
[0017] In another implementation, the first adhesive includes an acrylic adhesive.
[0018] In another implementation, the second adhesive includes a silicone adhesive.
[0019] In another implementation, the gasket contains a silicone elastomer.
[0020] In another implementation, the device includes a flow cell manifold coupled to a first end of a flow cell, and includes a flow cell manifold inlet, a plurality of fluid lines, and a plurality of flow cell manifold outlets fluidly coupled to the flow cell manifold inlet by the corresponding fluid lines. Each of the flow cell manifold outlets is coupled to a corresponding first channel opening of the flow cell.
[0021] In another implementation, the device includes a manifold gasket assembly coupled to the flow cell manifold inlet.
[0022] In another implementation, the manifold gasket assembly includes a first adhesive bonded to the flow cell manifold, a gasket, and a second adhesive bonded to the gasket and positioned between the first adhesive and the second adhesive.
[0023] In another implementation, the flow cell manifold includes a laminate.
[0024] In another implementation, the device includes a liner assembly comprising a release liner, a permanent adhesive, and a foil layer, the permanent adhesive bonding the foil layer and the release liner.
[0025] In another implementation, the liner assembly further includes a third adhesive and a polyethylene terephthalate layer. The third adhesive joins the foil layer and the polyethylene terephthalate layer.
[0026] In another implementation, the device includes a plurality of gasket assemblies. Each of the gasket assemblies is spaced apart and coupled to a release liner.
[0027] In another implementation, the plurality of gasket assemblies are coupled to a release liner to form a roll.
[0028] In another implementation, the flow cell interface includes a plurality of plungers that can engage with corresponding gaskets.
[0029] In another implementation, the device includes a spring that biases a corresponding plunger.
[0030] In another implementation, the flow cell interface includes a plunger guide that includes a plunger bore in which a corresponding plunger is positioned.
[0031] In another implementation, the system further includes a vacuum chuck that supports the flow cell.
[0032] In another implementation, the vacuum chuck supports a substantial length of the flow cell between a first end and a second end.
[0033] In another implementation, the device includes a flow cell frame to which the flow cell and the plurality of gasket assemblies are coupled.
[0034] In another implementation, the method includes pressing a gasket assembly toward a surface of a flow cell, thereby bonding a second side of an adhesive stack to the surface of the flow cell.
[0035] In another implementation, the method involves distributing gasket assemblies from a roll containing multiple gasket assemblies.
[0036] In another implementation, distributing the gasket assembly from the roll involves passing the gasket assembly through a guide.
[0037] In another implementation, the method involves using a sensor to detect the location of the gasket assembly before picking it up.
[0038] In another implementation, the adhesive stack includes a first adhesive on the first side of the adhesive stack, a second adhesive on the second side of the adhesive stack, and a separation layer positioned between the first adhesive and the second adhesive.
[0039] In another implementation, the first adhesive includes an acrylic adhesive, the second adhesive includes a silicone adhesive, and the separation layer includes a polyethylene terephthalate layer.
[0040] In another implementation, the gasket contains a silicone elastomer.
[0041] In another implementation, the gasket with adhesive backing includes an adhesive stack.
[0042] In another implementation, the adhesive stack includes polyethylene terephthalate between the acrylic adhesive and the silicone adhesive.
[0043] In another implementation, the silicone adhesive is adjacent to the gasket.
[0044] In another implementation, the gasket contains a silicone elastomer.
[0045] In another configuration, the device further includes a flow cell. A gasket with adhesive backing is coupled to the flow cell.
[0046] In another implementation, the device further includes a laminate and a flow cell. The laminate is coupled to the flow cell, and the gasket is coupled to the laminate.
[0047] In another implementation, a flow cell contains multiple channels.
[0048] It should be understood that all combinations of the aforementioned concepts and further concepts, which are described in more detail below (on the premise that such concepts are not contradictory), are considered to be part of the subject matter disclosed herein and / or can be combined to achieve specific interests in a particular aspect. Specifically, all combinations of the claimed subject matter appearing at the end of this disclosure are considered to be part of the subject matter disclosed herein. [Brief explanation of the drawing]
[0049] [Figure 1] A schematic diagram illustrating the implementation of the system as taught in this disclosure is provided as an example. [Figure 2] This is a detailed cross-sectional view of an exemplary implementation of a flow cell cartridge assembly illustrating the first portion of the flow cell interface and vacuum chuck of Figure 1, as well as the first end of the flow cell of Figure 1. [Figure 3] This is a detailed cross-sectional view of an exemplary implementation of a flow cell cartridge assembly illustrating the second portion of the flow cell interface and vacuum chuck in Figure 1, as well as the second end of the flow cell in Figure 1. [Figure 4] Figure 1 is an isometric enlarged view of an exemplary mounting configuration of a flow cell cartridge assembly. [Figure 5] Figure 4 is a bottom view of the flow cell cartridge assembly. [Figure 6] Figure 1 is an isometric enlargement of an exemplary mounting configuration of a gasket assembly, which includes an adhesive stack and gaskets, each defining a corresponding through-hole. [Figure 7]Figure 1 is an isometric enlarged view of an exemplary mounting configuration of the gasket assembly, illustrating the gasket, first adhesive, second adhesive, and separation layer. [Figure 8] Figure 1 illustrates a plan view of an alternative implementation of a flow cell that can be used in the system shown in Figure 1. [Figure 9] This is a system that can be used to assemble a flow cell as taught in this disclosure. [Figure 10] Figure 9 illustrates an isometric view of a head that can be used in the system shown. [Figure 11] This is a cross-sectional view of a portion of a roll of gasket assembly that can be used in the system shown in Figure 9. [Figure 12] A flowchart illustrating a method for assembling either a portion of the flow cell cartridge assembly shown in Figure 1 or any of the flow cells disclosed herein, using the system shown in Figure 9, is illustrated. [Modes for carrying out the invention]
[0050] The following text discloses detailed descriptions of implementations of the method, apparatus, and / or product, but it should be understood that the legal scope of ownership is defined by the claims set out at the end of this patent. Therefore, the following “Modes for Carrying Out the Invention” should be interpreted as illustrative only and do not describe all possible implementations, as it would be impractical, if not impossible, to describe all possible implementations. Numerous alternative implementations may be implemented using either the current art or art developed after the filing date of this patent. Such alternative implementations are expected to still fall within the scope of the claims.
[0051] This disclosure relates to a flow cell cartridge assembly comprising a flow cell having multiple channels. The flow cell may or may not include a flow cell manifold having a single inlet and multiple outlets. The outlets of the flow cell manifold are coupled to the channels of the flow cell. Gaskets may be provided at the channel outlets to facilitate fluid coupling between the channels and an associated system, for example, used to perform analysis of a sample of interest. The gaskets may span the width of the flow cell and have holes corresponding to the outlets of each channel. While a single gasket is effective in establishing a sealing connection between the flow cell and the associated system, if the flow cell comprises multiple channels (e.g., eight channels), the stack-up of alignment between the gasket and the channel outlets may be poor. Although the above example refers to a flow cell comprising multiple channels, the flow cell as taught in this disclosure may comprise a single channel.
[0052] At least one aspect of this disclosure relates to flow cell cartridge assemblies and associated systems that enable a reduction in manufacturing tolerances and, furthermore, a reduction in the amount of force that may be involved in establishing a fluid connection between the flow cell and the system. In some implementations, a fluid connection between the system and the flow cell can be established using a force of about 1.2 Newtons (N) or less. For example, the gaskets and associated methods disclosed herein offer approximately 30% reduction in sealing force compared to other methods, such as gaskets coupled by brackets, thereby significantly reducing the size and complexity of the flow cell housing. The smaller sealing force also results in less warping of the flow cell, which can lead to improved optical and thermal interfaces. Thus, the disclosed implementations reduce the possibility that a fluid connection will not be established between the flow cell and the system, and furthermore, reduce the possibility that the engagement between the flow cell and the system will adversely affect the flatness of the flow cell.
[0053] By using the disclosed mounting configuration, a reduction in common line volume may also be possible compared to gaskets bonded by brackets. The back-adhesive gaskets disclosed herein may also enable stack-up with smaller tolerances for port alignment and fewer moving parts. The gaskets and related methods of use and manufacture also offer the benefits and advantages of flexible design for accommodating multi-configuration flow cells.
[0054] The disclosed flow cell cartridge assembly includes a back-adhesive gasket that is individually bonded to each of the outlets of the respective channels and to the inlet of the flow cell manifold. Alternatively, the flow cell manifold may be omitted, and the back-adhesive gasket may be bonded to the inlet of each channel. The back-adhesive gasket may include an adhesive stack and a gasket, the adhesive stack having a first side bonded to the gasket and a second side bonded to the flow cell.
[0055] The adhesive stack may include a first adhesive bonded to the flow cell and a second adhesive bonded to the gasket and positioned between the first adhesive and the gasket. The inclusion of two adhesives allows the back-adhesive gasket to bond to both a flow cell made of glass and a gasket made of silicone elastomer. The adhesive stack may also include a separator layer positioned between the first and second adhesives. The first adhesive can bond to both the flow cell and the separator layer, and the second adhesive can bond to both the separator layer and the gasket. In some implementations, the first adhesive is an acrylic adhesive, the second adhesive is a silicone adhesive, and the separator layer is polyethylene terephthalate (PET). However, other types of adhesives or separator layers may be used.
[0056] In some implementations, gaskets may be supplied on a tape reel so that they can be fed to a precision pick-and-place (PNP) machine using a label feeder concept. This may involve feeding the gaskets onto the non-stick surface of the label feeder for automated assembly, allowing the head of a vacuum nozzle to pick up the gaskets and place them on the flow cell.
[0057] At least some of the exemplary gaskets described herein, and the methods of using / applying the gaskets to flow cells, help to significantly reduce the sealing force of the manifold, thereby reducing the complexity and / or cost of the flow cell holder architecture. Pick-and-place machines may be used for assembly, i.e., to apply the back-adhesive gaskets to the flow cells or to laminated structures that support or are fluidly connected to the flow cells. In some embodiments, a pick-and-place machine is used to pick up a gasket from a label feeder and then align and position the gasket over / around a hole in the flow cell, which acts as a port providing fluid access to the flow channels of the flow cell.
[0058] Figure 1 illustrates a schematic diagram of an implementation of System 100 as taught in this disclosure. System 100 can be used to perform analysis on one or more samples of interest. The samples may include one or more DNA clusters linearized to form single-stranded DNA (sstDNA). In the shown implementation, System 100 is adapted to receive a flow cell cartridge assembly 102, which includes a flow cell 103 and a sample cartridge 104, and also partially includes a shipper manifold assembly 106, a sample loading manifold assembly 108, and a pump manifold assembly 110. System 100 also includes a drive assembly 112, a controller 114, an imaging system 116, and a waste reservoir 118. The controller 114 is electrically and / or communicatively coupled to the drive assembly 112 and the imaging system 116, and is adapted to cause the drive assembly 112 and / or the imaging system 116 to perform various functions disclosed herein.
[0059] System 100 includes a flow cell receptacle 122 for receiving a flow cell cartridge assembly 102, a vacuum chuck 124 for supporting a flow cell 103, and a flow cell interface 126 used to establish a fluid coupling between System 100 and the flow cell 103. The flow cell interface 126 may include one or more manifolds.
[0060] First, referring to the flow cell 103, in the shown implementation, the flow cell 103 includes a plurality of channels 128, each channel having a first channel opening 130 located at the first end 132 of the flow cell 103 and a second channel opening 134 located at the second end 135 of the flow cell 103. Depending on the direction of flow through the channel 128, either the channel openings 130 or 134 can act as an inlet or outlet. In Figure 1, the flow cell 2 is shown to include two channels 128, but it may include any number of channels 128 (e.g., one, two, six, or eight) (see Figures 5 and 8).
[0061] The flow cell cartridge assembly 102 also includes a flow cell frame 136, a flow cell manifold 137 coupled to the first end 132 of the flow cell 103, and a plurality of gasket assemblies 138 coupled to the corresponding second channel opening 134. As used herein, a “flow cell” (also referred to as a “flowcell”) may include a device having a lid extending over a reaction structure to form flow channels between the flow cells communicating with a plurality of reaction sites of the reaction structure. Some flow cells may also include a detection device for detecting a specified reaction occurring at or near a reaction site. As shown, the flow cell 103, the flow cell manifold 137, and the gasket assemblies 138 are coupled together or otherwise carried by the flow cell frame 136. The flow cell frame 136 is shown as being included in the flow cell cartridge assembly 102 in Figure 1, but the flow cell frame 136 may be omitted. Thus, the flow cell 103 and its associated gasket assembly 138 can be used in system 100 without the flow cell frame 136.
[0062] In the shown configuration, the flow cell manifold 137 may be a laminate and may include a single inlet 140 and a plurality of outlets 142, each coupled to the inlet 140 by a plurality of fluid lines 144 (the fluid lines 144 are clearly shown in Figure 5). One of the gasket assemblies 138 is also coupled to the inlet 140 of the flow cell manifold 137. The outlets 142 of the flow cell manifold 137 are aligned with and positioned adjacent to the first flow cell opening 130. In this way, fluid can flow between the outlets 142 of the manifold 137 and the first opening 130 of the channel 128. The flow cell cartridge assembly 102 in Figure 1 is shown to include the flow cell manifold 137, but in other configurations, the flow cell manifold 137 may be omitted. If the flow cell manifold 137 is omitted, the gasket assembly 138 can be coupled to the first channel opening 130 in a manner similar to the coupling between the gasket assembly 138 and the flow cell 103 at the second channel opening 134.
[0063] Referring to gasket assembly 138, in the shown configuration, each gasket assembly 138 includes an adhesive stack 146 and a gasket 148. The adhesive stack 146 has a first side 150 bonded to the gasket 148 and a second side 152 bonded to the flow cell 103. The adhesive stack 146 and gasket 148 form an annular, back-adhesive gasket, and the adhesive stack 146 may be formed from a double-sided pressure-sensitive adhesive tape. The second side 152 of the adhesive stack 146 may be bonded to the flow cell 103 using an adhesive or covalent bond. A covalent bond may be formed, for example, by activating the glass of the flow cell 103, activating the second side 152 of the adhesive stack 146 made of silicone, and bringing the flow cell 103 and the second side 152 of the adhesive stack 146 into contact with each other. The second side 152 of the glass and / or adhesive stack 146 of the flow cell 103 can be activated by altering the surface energy of the material to suit specific properties such as hydrophobicity, reactivity, bonding properties, and / or morphology. Heat and / or pressure may be used further or alternatively to activate the second side 152 of the glass and / or adhesive stack 146 of the flow cell 103.
[0064] During operation, the flow cell interface 126 engages with the corresponding gasket 148 to establish a fluid bond between the system 100 and the flow cell 103. The engagement between the flow cell interface 126 and the gasket assembly 138 reduces or eliminates fluid leakage between the flow cell interface 126 and the flow cell 103.
[0065] Further referring to the gasket assembly 138, the adhesive stack 146 and the gasket 148 are aligned with each other and have through-holes 154, 156 that allow fluid communication through the gasket assembly 138. Thus, fluid can flow through the gasket assembly 138 into and / or out of the flow cell 103. In the shown configuration, the adhesive stack 146 includes a first adhesive 158 bonded to the flow cell 103 and a second adhesive 160 bonded to the gasket 148 and positioned between the first adhesive 158 and the gasket 148. The adhesive stack 146 also includes a separator 162 positioned between the first adhesive 158 and the second adhesive 160. The first adhesive 158 bonds to both the flow cell 103 and the separator 162, and the second adhesive 160 bonds to both the separator 162 and the gasket 148.
[0066] To allow fluid to pass through the gasket assembly 138, the separation layer 162 defines a through-hole 154 that aligns with the through-hole 156 of the gasket 148. In the shown configuration, the first adhesive 158 coats the first side 166 of the separation layer 162, and the second adhesive 160 coats the second side 168 of the separation layer 162. The first adhesive 158 and / or the second adhesive 160 can completely coat the separation layer 162, partially coat it, or form a pattern thereon.
[0067] The first adhesive 158 may be an acrylic adhesive, the second adhesive 160 may be a silicone adhesive, the separation layer 162 may contain polyethylene terephthalate (PET), and the gasket 148 may be a silicone elastomer. The gasket 148 may contain, or be formed from, a silicone sheet, Dynaflex® G7702 (TPE), platinum-cured silicone, Santoprene 8281-35 (TPV), a thermoplastic elastomer, a polypropylene polymer, synthetic rubber, a thermoplastic vulcanized product, etc. However, different adhesives may be used for either the first adhesive 158 and / or the second adhesive 160, and / or different elastomers may be used for the gasket 148. For example, the first adhesive 158 of the gasket assembly 138 bonded to the flow cell manifold 137 may be bondable to a flow cell manifold 137 made of PET, while the first adhesive 158 of the gasket assembly 138 bonded to the flow cell 102 may be bondable to a flow cell 103 made of glass. However, the flow cell manifold 137 and / or flow cell 103 may be made of materials other than those described, including the flow cell manifold 137 and / or flow cell 103 made of the same material.
[0068] Referring here to the sample cartridge 104, the sample loading manifold assembly 108, and the pump manifold assembly 110, in the shown implementation, the system 100 includes a sample cartridge receptacle 170 that receives the sample cartridge 104 carrying one or more samples of interest (e.g., specimens). The system 100 also includes a sample cartridge interface 172 that establishes a fluid connection with the sample cartridge 104.
[0069] The sample loading manifold assembly 108 includes one or more sample valves 174, and the pump manifold assembly 110 includes one or more pumps 176, one or more pump valves 178, and a cache 180. One or more of the valves 174, 178 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezoelectric valves, and / or three-way valves. However, different types of fluid control devices may be used. One or more of the pumps 176 may be implemented by syringe pumps, peristaltic pumps, and / or diaphragm pumps. However, other types of fluid transfer devices may be used. The cache 180 may be a meandering cache and may temporarily store one or more reactants during bypass operation of system 100 in Figure 1, for example. Although the cache 180 is shown as being included in the pump manifold assembly 110, in other implementations the cache 180 may be located in a different location. For example, the cache 180 may be located within the shipper manifold assembly 106, or within another manifold downstream of the bypass fluid line 182.
[0070] The sample loading manifold assembly 108 and the pump manifold assembly 110 transport one or more samples of interest from the sample cartridge 104 to the flow cell cartridge assembly 102 through the fluid line 184. In some implementations, the sample loading manifold assembly 108 can load / handle samples of interest individually into each channel 128 of the flow cell 125. The process of loading samples of interest into the channels 128 can be performed automatically using the system 100 in Figure 1.
[0071] As shown in system 100 of Figure 1, the sample cartridge 104 and the sample loading manifold assembly 108 are positioned downstream of the flow cell cartridge assembly 102. Thus, the sample loading manifold assembly 108 can load the sample of interest into the flow cell 103 from the rear. Loading the sample of interest from the rear of the flow cell 103 may be referred to as "rear loading." Rear loading the sample of interest into the flow cell 103 can reduce contamination. In the shown configuration, the sample loading manifold assembly 108 is coupled between the flow cell cartridge assembly 102 and the pump manifold assembly 110.
[0072] To draw the sample of interest from the sample cartridge 104 toward the pump manifold assembly 110, the sample valve 174, the pump valve 178, and / or the pump 176 can be selectively activated to bias the sample of interest toward the pump manifold assembly 110. The sample cartridge 104 may include multiple sample reservoirs that are selectively fluid-accessible via the corresponding sample valves 174. Thus, each sample reservoir can be selectively isolated from other sample reservoirs using the corresponding sample valve 174.
[0073] The sample valve 174, pump valve 178, and / or pump 176 can be selectively activated to selectively flow the sample of interest to the corresponding channel 128 of the flow cell 103 toward the flow cell cartridge assembly 102, and away from the pump manifold assembly 110. In some implementations, each channel 128 of the flow cell 103 accepts the sample of interest. In other implementations, one or more channels 128 selectively accept the sample of interest, while the other channels 128 do not. Channels 128 of the flow cell 103 that cannot accept the sample of interest may, for example, accept a wash buffer instead.
[0074] The drive assembly 112 interfaces with the shipper manifold assembly 106 and the pump manifold assembly 110 to flow one or more reagents that interact with the sample in the flow cell 103. In one implementation, a reversible terminator is attached to the reagent to allow a single nucleotide to be incorporated into a growing DNA strand. In some such implementations, one or more of the nucleotides have a unique fluorescent label that emits a color when excited. The color (or lack thereof) is used to detect the corresponding nucleotide. In the implementation shown, the imaging system 116 excites one or more of the identifiable labels (e.g., fluorescent labels) and then acquires image data of the identifiable labels. The labels may be excited by incident light and / or laser, and the image data may include one or more colors emitted by each label in response to excitation. The image data (e.g., detection data) may be analyzed by system 100. The imaging system 116 may be a fluorescence spectrophotometer including an objective lens and / or a solid-state imaging device. Solid-state imaging devices may include charge-coupled devices (CCDs) and / or complementary metal oxide semiconductors (CMOSs).
[0075] After image data is obtained, the drive assembly 112 interfaces with the shipper manifold assembly 106 and the pump manifold assembly 110 to flow another reaction component (e.g., a reagent) through the flow cell 103, which is then received by the waste reservoir 118 via the main waste fluid line 186 and / or discharged otherwise by the stem 100. Some reaction components perform a flushing operation that chemically cleaves the fluorescently labeled and reversible terminators from the sstDNA. The sstDNA is then ready for another cycle.
[0076] The main waste fluid line 186 is coupled between the pump manifold assembly 110 and the waste reservoir 118. In some implementations, the pump 176 and / or pump valve 178 of the pump manifold assembly 110 selectively deliver the reactive components from the flow cell cartridge assembly 102 to the main waste fluid line 186 through the fluid line 184 and the sample loading manifold assembly 108.
[0077] The flow cell cartridge assembly 102 is coupled to the central valve 188 via the flow cell interface 126. The auxiliary waste fluid line 190 is coupled to the central valve 188 and the waste reservoir 118. In some implementations, the auxiliary waste fluid line 190 receives excess fluid from the sample of interest from the flow cell cartridge assembly 102 via the central valve 188 when the sample of interest is rear-loaded into the flow cell 103, as described herein, and directs the excess fluid from the sample of interest to the waste reservoir 117. That is, the sample of interest may be loaded from the rear of the flow cell 103, and any excess fluid from the sample of interest may exit from the front of the flow cell 103. By rear-loading the sample of interest into the flow cell 103, different samples can be loaded separately into the corresponding channels 128, and a single flow cell manifold 137 can connect the front of the flow cell 103 to the central valve 188 to direct the excess fluid from each sample of interest to the auxiliary waste fluid line 190. Once the sample of interest is loaded into the flow cell 103, the flow cell manifold 137 can be used to deliver common reagents from the front (e.g., upstream) of the flow cell 103 through each channel 128, and the common reagents exit from the rear (e.g., downstream) of the flow cell 125. In other words, the sample of interest and the reagents can flow in opposite directions through the channels 128 of the flow cell 103.
[0078] Referring to shipper manifold assembly 106, in the shown implementation, shipper manifold assembly 106 includes a shared line valve 192 and a bypass valve 194. The shared line valve 192 may be referred to as a reagent selector valve. The central valve 188 and the valves 192 and 194 of shipper manifold assembly 106 can be selectively actuated to control the flow of fluid through the fluid lines 196, 198, and 200. One or more of the valves 196, 198, and 200 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezoelectric valves, etc. Other fluid control devices may be found to be suitable.
[0079] The shipper manifold assembly 106 may be coupled to a corresponding number of reagent reservoirs 202 via reagent shippers 204. The reagent reservoirs 202 may contain a fluid (e.g., a reagent and / or another reactant). In some implementations, the shipper manifold assembly 106 includes multiple ports. Each port of the shipper manifold assembly 106 may accept one of the reagent shippers 204. The reagent shippers 204 may be referred to as fluid lines.
[0080] The shared line valve 192 of the shipper manifold assembly 106 is connected to the central valve 188 via the shared reagent fluid line 196. Different reagents may flow through the shared reagent fluid line 196 at different times. In one implementation configuration, when performing a flushing operation before changing one reagent with another, the pump manifold assembly 110 may draw wash buffer through the shared reagent fluid line 196, the central valve 188, and the flow cell cartridge assembly 102. Thus, the shared reagent fluid line 196 may be involved in the flushing operation. Although one shared reagent fluid line 196 is shown, any number of shared fluid lines may be included in the system 100.
[0081] The bypass valve 194 of the shipper manifold assembly 106 is connected to the central valve 188 via dedicated reagent fluid lines 198, 200. The central valve 188 may have one or more dedicated ports corresponding to the dedicated reagent fluid lines 198, 200. Each of the dedicated reagent fluid lines 198, 200 may be associated with a single reagent. The fluids that may flow through the dedicated reagent fluid lines 198, 200 may be used during sequencing operations and may include cutting reagents, embedding reagents, scanning reagents, cutting wash solutions, and / or wash buffers. Therefore, when performing a flushing operation before changing one reagent with another in association with the bypass valve 194, the shipper manifold assembly 106 may draw wash buffers through the central valve 188 and / or the flow cell cartridge assembly 102. However, since only a single reagent can flow through each of the dedicated reagent fluid lines 198, 200, the dedicated reagent fluid lines 198, 200 themselves cannot be flushed. The method, which includes dedicated reagent fluid lines 198 and 200, may be advantageous when system 100 uses reagents that may have adverse reactions with other reagents. Furthermore, by reducing the number or length of fluid lines that are flushed when switching between different reagents, reagent consumption and flush volume can be reduced, thereby decreasing the cycle time of system 100. Although two dedicated reagent fluid lines 198 and 200 are shown, any number of dedicated fluid lines may be included in system 100.
[0082] The bypass valve 194 is also connected to the cache 180 of the pump manifold assembly 110 via the bypass fluid line 182. One or more reagent priming, hydration, mixing, and / or transfer operations can be performed using the bypass fluid line 182. The priming, hydration, mixing, and / or transfer operations can be performed independently of the flow cell cartridge assembly 102. Therefore, operations using the bypass fluid line 182 can be performed, for example, during the incubation of one or more samples of interest in the flow cell cartridge assembly 102. That is, the shared line valve 192 can be used independently of the bypass valve 194, so that while the shared line valve 192 and / or the central valve 188 are performing other operations simultaneously, substantially simultaneously, or in offset synchronization, the bypass valve 194 can use the bypass fluid line 182 and / or the cache 180 to perform one or more operations. Thus, the system 100 can perform multiple operations at once, thereby reducing execution time.
[0083] Referring here to the drive assembly 112, in the shown implementation, the drive assembly 112 includes a pump drive assembly 206 and a valve drive assembly 208. The pump drive assembly 206 may be adapted to interface with one or more pumps 176 to pump fluid through the flow cell 103 and / or to load one or more samples of interest into the flow cell 103. The valve drive assembly 208 may be adapted to interface with one or more valves 174, 178, 188, 192, 194 to control the position of the corresponding valves 174, 178, 188, 192, 194.
[0084] Referring to controller 114, in the disclosed implementation, controller 114 includes a user interface 210, a communication interface 212, one or more processors 214, and a memory 216 that stores instructions executable by one or more processors 214 for performing various functions, including those in the disclosed implementation. The user interface 210, the communication interface 133, and the memory 216 are electrically and / or communicatively coupled to one or more processors 214.
[0085] In one implementation, the user interface 210 is adapted to receive input from the user and provide the user with information associated with the operation of the system 100 and / or the analysis performed. The user interface 210 may include a touchscreen, display, keyboard, speaker, mouse, trackball, and / or voice recognition system. The touchscreen and / or display may display a graphical user interface (GUI).
[0086] In one implementation, the communication interface 212 is adapted to enable communication between system 100 and a remote system (e.g., a computer) over a network. Examples of networks include the Internet, intranet, local area network (LAN), wide area network (WAN), coaxial cable network, wireless network, wired network, satellite network, digital subscriber line (DSL) network, cellular network, Bluetooth connection, and near-field communication (NFC) connection. Some of the communication provided to the remote system may be associated with analysis results, imaging data, etc., generated by system 100 or acquired by other means. Some of the communication provided to system 100 may be associated with fluid analysis operations, patient records, and / or protocols performed by system 100.
[0087] One or more processors 214 and / or system 100 may include one or more processor-based systems or microprocessor-based systems. In some implementations, one or more processors 214 and / or system 100 may include one or more programmable processors, programmable controllers, microprocessors, microcontrollers, graphics processing units (GPUs), digital signal processors (DSPs), reduced-instruction-set computers (RISCs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), field-programmable logic devices (FPLDs), logic circuits, and / or other logic-based devices that perform various functions, including those described herein.
[0088] Memory 216 includes semiconductor memory, magnetically readable memory, optical memory, hard disk drives (HDDs), optical storage drives, solid-state storage devices, solid-state drives (SSDs), flash memory, read-only memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), random-access memory (RAM), non-volatile RAM (NVRAM), compact discs (CDs), compact disc read-only memory (CD-ROMs), digital versatile discs (DVDs), Blu-ray discs, and redundant arrays of independent discs. This may include one or more of the following: disks, RAID systems, caches, and / or any other storage devices or storage disks on which information is stored for any duration (e.g., permanently, temporarily, over a long period, for buffering, for caching).
[0089] Figure 2 is a detailed cross-sectional view of an exemplary configuration of a flow cell cartridge assembly 102 illustrating the first portion 250 of the flow cell interface 126 and the vacuum chuck 124 of Figure 1, as well as the first end 132 of the flow cell 103 of Figure 1. The first portion 250 of the flow cell interface 126 is positioned to establish a fluid connection with the gasket assembly 138 associated with the flow cell manifold 137 of the flow cell cartridge assembly 102.
[0090] In the shown configuration, the first portion 250 of the flow cell interface 126 includes a plunger guide 252, which includes a plunger bore 254 in which a plunger 256 is positioned. A spring 258 is positioned and shown to engage with the corresponding gasket assembly 138, biasing the corresponding plunger 256 generally in the direction indicated by arrow 260. The plunger 256 defines a fluid path 262 through which fluid can pass. As also shown in Figure 2, the vacuum chuck 124 supports the substantial width 266 of the flow cell 103. Additionally, the vacuum chuck 124 may support the substantial length or entire length of the flow cell 103 between end 132 and end 135.
[0091] Figure 3 is a detailed cross-sectional view of an exemplary configuration of a flow cell cartridge assembly 102 illustrating the second portion 268 of the flow cell interface 126 and the vacuum chuck 124 of Figure 1, as well as the second end 135 of the flow cell 103 of Figure 1. The second portion 268 of the flow cell interface 126 is positioned to establish a fluid connection with the gasket assembly 138 at the second end 135 of the flow cell 103.
[0092] In the shown configuration, the second portion 268 of the flow cell interface 126 includes a plunger guide 252 which includes a plunger bore 254 in which the corresponding plunger 256 is positioned. The spring 258 biases the corresponding plunger 256 generally in the direction indicated by arrow 260 to position it to engage with the corresponding gasket assembly 138.
[0093] Figure 4 is an isometric enlargement view of an exemplary implementation of the flow cell cartridge assembly 102 of Figure 1. In the shown implementation, the flow cell cartridge assembly 102 includes a flow cell frame 136, a flow cell 103 having a plurality of channels 128, a flow cell manifold 137, and a gasket assembly 138. The flow cell cartridge assembly 102 also includes a radio frequency identification (RFID) tag 270 used for tracking and / or identification purposes, and a plurality of retaining clips 272 used to hold the flow cell 103, the flow cell manifold 137, and / or the RFID tag 270 in or against the flow cell frame 136.
[0094] Referring to the flow cell frame 136, in the shown configuration, the flow cell frame 136 has a peripheral wall 274 and a top surface 276. The peripheral wall 274 and the top surface 276 define a cavity 278. The cavity 278 includes an upper opening 280 and a lower opening 282. The upper opening 280 is defined by the top surface 276 and may allow image data of the flow cell 103 to be acquired using the imaging system 116. The lower opening 282 is defined by the lower edge 284 of the peripheral wall 274 and may allow a sample of interest to be loaded into the channel 128 of the flow cell 103 through different gasket assemblies 138.
[0095] Figure 5 is a bottom view of the flow cell cartridge assembly 102 of Figure 4. As shown, the flow cell manifold 137 includes a single inlet 140, a fluid line 144, and an outlet 142. As described above, the inlet 140 of the flow cell manifold 137 is connected to each of the outlets 142 via the fluid line 144. The flow cell manifold 137 and its fluid line 144 may allow control of the fluid flow through the flow cell cartridge assembly 102 using fewer valve configurations.
[0096] Figure 6 is an isometric enlargement of an exemplary mounting configuration of the gasket assembly 138 of Figure 1, which includes an adhesive stack 146 and a gasket 148, each defining one of the corresponding through-holes 154, 156. The gasket 148 may be formed from a silicone sheet, and the adhesive stack 146 may be a double-sided coated tape having PET and / or a transfer adhesive. Generally, the gasket assembly 138 may include a heat-resistant adhesive, and the gasket material may be able to withstand multiple thermal cycles at about 20°C to about 60°C and have a shelf life of about 18 months with respect to the material.
[0097] To form the adhesive stack 146 and / or gasket 148, the adhesive stack 146 and / or gasket 148 can be cut using a laser cutting process, a die cutting process, a knife / burr cutting process, and / or a waterjet cutting process. These or other processes allow the gasket 148 to be formed with fewer defects and with or without adhesion defects.
[0098] Figure 7 is an isometric enlargement of an exemplary mounting configuration of the gasket assembly 138 of Figure 1, illustrating the gasket 148, the first adhesive 158, the second adhesive 160, and the separation layer 162. In some mounting configurations, the gasket assembly 138 has a diameter of approximately 4 mm ± 0.2 mm, the through holes 154 and / or 156 have a diameter of approximately 1 mm ± 0.1 mm, the gasket 148 has a thickness of approximately 1.0 mm ± 0.1 mm, the gasket 148 has a hardness of approximately 30 Shore A ± 5 Shore A, and the adhesive stack 146 has a thickness of approximately 75 micrometers (μm). The thickness and / or diameter are mentioned in relation to the gasket assembly 138 and / or its components 148, 154, 156, 158, 160, and 162, but it may be found that other sizes and / or diameters are preferable.
[0099] Figure 8 illustrates a plan view of another implementation configuration of the flow cell 103 that can be used in the system 100 of Figure 1. In contrast to the implementation configuration in Figure 4, the flow cell 103 in Figure 8 includes two channels 128 and has a smaller width. The gasket assembly 138 is not shown coupled to the flow cell 103 in Figure 8, but the gasket assembly 138 may be included in a manner similar to how the gasket assembly 138 is coupled to the flow cell 103 in Figure 4. Although two channels 128 are shown, any number of channels may be included instead, such as six channels or one channel. If the flow cell 103 includes one channel, the flow cell manifold 137 may be omitted.
[0100] Figure 9 shows a system 300 that can be used to assemble a flow cell 103 as taught in this disclosure. In the shown configuration, the system 100 includes a pick-and-place machine 302, a gasket feeder 304, and a carrier 306 for receiving the flow cell 103 during the assembly process. The pick-and-place machine 302 may be a Fuji pick-and-place (PNP) machine and may include a head 308 used to pick up and position a gasket assembly 138, and a sensor 310 used to acquire position data. The position data may include the positions of the gasket assembly 138 and / or the flow cell 103 being assembled, and may also be used to identify a flow cell reference point, a flow cell manifold reference point, and / or a gasket assembly 138 reference point through optical detection or other processes.
[0101] The head 308 of the pick-and-place machine 302 includes a pair of arc-shaped apertures 313 that define a recess 311 for receiving the end portion 312 of the gasket assembly 138, thereby creating a coupling between the head 308 and the gasket assembly 138. The gasket feeder 304 has a spool 314 that receives a roll 315 containing the gasket assembly 138 on a tape 316. The tape 316 may be a low-tack tape and may be referred to as a liner assembly. The gasket feeder 304 also includes a guide 318 for guiding the tape 316 as the gasket assembly 138 is distributed during the assembly process, and a sensor 320 for sensing when the gasket assembly 138 is in a pick-up position 322 on the gasket feeder 304. In response to the sensor 320 sensing the gasket assembly 138 in the pick-up position 322, the gasket feeder 304 may stop feeding the gasket assembly 138, for example, until the gasket assembly 138 in the pick-up position 322 is picked up by the head 308.
[0102] During operation, the pick-and-place machine 302 acquires position data from sensors 310 and / or 320, and based on this position data, the pick-and-place machine 302 causes the head 308 to pick up one or more gasket assemblies 138 from the tape 316 and align the gasket assembly 138 with one of the second openings 134 of the channel 128 of the flow cell 103. Once aligned, the head 308 moves and presses the gasket 138 to engage with the flow cell 103, thereby coupling the gasket assembly 138 to the flow cell 103 at the corresponding second channel opening 134. The pick-and-place machine 302 may repeat the process of coupling the gasket assemblies 138 to the flow cell 103 until each of the second channel openings 134 has one of the gasket assemblies 138 mounted adjacent to it. The pick-and-place machine 302 may also, in a similar manner, attach the flow cell manifold 137 and associated gasket assembly 138 to the first end 132 of the flow cell 103. In an implementation where the flow cell manifold 137 is omitted, the pick-and-place machine 302 may connect the corresponding gasket assembly 138 to each of the first channel openings 130 in a similar manner to when the gasket assembly 138 is connected to the second channel opening 134.
[0103] Next, the flow cell assembly, including the flow cell 103 and associated components 137, 138, can be removed from the carrier 306 and / or system 100. Quality control procedures may be performed on the flow cell 103, for example, including scanning the flow cell 103 and / or a pressure test of the flow cell 103 to verify its fluid integrity. A barcode label may be attached to the flow cell 103. After the quality tests have been performed, the flow cell assembly can be secured within the flow cell frame 136.
[0104] Figure 10 illustrates an isometric view of a head 308 that can be used in the system 100 of Figure 9. In the shown configuration, the head 308 includes an end portion 312 of the gasket assembly 138 and an end portion 324 including a recess 311 for receiving an arc-shaped aperture 313. The arc-shaped aperture 313 may extend through the length of the head 308 or a portion of the length of the head 308.
[0105] Figure 11 is a cross-sectional view of a portion of a roll 315 of a gasket assembly 138 that can be used in the system 100 of Figure 9. In the shown configuration, the roll 315 includes the gasket assembly 138 and a tape 316 to which the gasket assembly 138 is removably bonded. The tape 316 includes a release liner 352, a permanent adhesive 354, and a foil layer 356. The permanent adhesive 364 can bond the foil layer 356 and the release liner 352, ensuring that the release liner 352 does not detach with the gasket assembly 138 when the gasket assembly 138 is removed. The foil layer 356 may be used to prevent the laser from cutting through the entire tape 316 during the laser cutting process, leaving the gasket assembly 138 on the release liner 352 so that it can be easily removed.
[0106] In some configurations, dry ice cleaning may be used to remove the debris. The tape 316 also includes a third adhesive 358 and a PET layer 360. The third adhesive 358 bonds the foil layer 356, and the PET layer 360 may prevent wrinkles in the foil layer 356. In other configurations, the third adhesive 358 may be a barrier coating, and the PET layer 360 may be a heat-seal coating. A liner 362 may also be provided on top of the gasket assembly 138 to prevent the gasket assembly 138 from bonding to another layer of tape 316 on the roll 315. As shown in Figure 11, to produce a roll 315 with a single row of gasket assemblies 138, a larger roll with multiple rows (e.g., four rows) of gasket assemblies 138 may be cut using a cutting machine.
[0107] Figure 12 illustrates a flowchart illustrating a method for assembling either a portion of the flow cell cartridge assembly 102 of Figure 1 or a flow cell 103 disclosed herein, using the system 300 of Figure 9. The execution order of the blocks may be changed, and / or some of the described blocks may be changed, omitted, combined, and / or subdivided into multiple blocks.
[0108] Process 1200 begins with distributing the gasket assemblies 138 from a roll 315 containing multiple gasket assemblies 138 (block 1202). Distributing the gasket assemblies 138 from the roll 315 may include passing the gasket assemblies 138 through the guides 318 of the gasket feeder 304. The location of the gasket assemblies 138 is detected using a sensor 320 (block 1204). The location of the gasket assemblies 138 may be associated with the gasket assembly 138 being located at a pick-up position 322. The gasket assembly 138 is picked up using the head 324 of the pick-and-place machine 302 (block 1206). The gasket assembly 138 includes an adhesive stack 146 and gaskets 148. The adhesive stack 146 has a first side 150 bonded to the gasket 148 and includes a first adhesive 158 on the first side 150 of the adhesive stack 146, a second adhesive 160 on the second side 152 of the adhesive stack 146, and a separator layer 162 positioned between the first adhesive 158 and the second adhesive 160. In some implementations, the first adhesive 158 includes an acrylic adhesive, the second adhesive 160 includes a silicone adhesive, and the separator layer 162 includes a polyethylene terephthalate layer.
[0109] The second side 152 of the gasket assembly 138 is positioned on the surface surrounding the openings 130 and 134 of the channel 128 of the flow cell 103 (block 1208), and the gasket assembly 138 is pressed toward the surface of the flow cell 103, thereby bonding the second side 152 of the adhesive stack 146 to the surface of the flow cell 103 (block 1210).
[0110] The foregoing description is provided to enable those skilled in the art to implement the various configurations described herein. While the subject art has been described in particular with reference to various figures and configurations, it should be understood that these are for illustrative purposes only and should not be construed as limiting the scope of the subject art.
[0111] In this specification, any element or process described in the singular and followed by the words "a" or "an" should be understood not to exclude multiple such elements or processes unless such exclusion is explicitly stated. Furthermore, references to "one implementation" are not intended to be interpreted as excluding the existence of additional implementations that also incorporate the listed features. Moreover, unless explicitly stated otherwise, an implementation that "comprises," "includes," or "having" one or more elements having a particular characteristic may include additional elements, whether or not they possess that characteristic. Furthermore, the terms "comprising," "including," and "having" are used interchangeably in this specification.
[0112] The terms “substantially,” “approximately,” and “about” as used throughout this specification are used to describe and account for small variations resulting from processing variability, etc. For example, they may refer to ±5% or less, e.g., ±2% or less, e.g., ±1% or less, e.g., ±0.5% or less, e.g., ±0.2% or less, e.g., ±0.1% or less, e.g., ±0.05% or less.
[0113] Many other methods may exist for carrying out the subject art. Various functions and elements described herein may be divided in ways different from those shown without departing from the scope of the subject art. Various modifications to these implementations may be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other implementations. Thus, many changes and modifications can be made to the subject art by those skilled in the art without departing from the scope of the subject art. For example, a different number of a given module or unit may be used, different or more types of a given module or unit may be used, a given module or unit may be added, or a given module or unit may be omitted.
[0114] Underlined and / or italicized headings and subheadings are used solely for convenience and do not limit the subject art, nor are they referenced in connection with the interpretation of the description of the subject art. All structural and functional equivalents of elements of various implementations described throughout this disclosure, which are known to those skilled in the art or will become known thereafter, are expressly incorporated herein by reference and are intended to be included in the subject art. Furthermore, nothing disclosed herein is intended to be for publication only, whether such disclosure is expressly stated in the above description or not.
[0115] It should be understood that all combinations of the aforementioned concepts and further concepts, which are described in more detail below (on the premise that such concepts are not contradictory), are considered to be part of the subject matter disclosed herein. Specifically, all combinations of the claimed subject matter appearing at the end of this disclosure are considered to be part of the subject matter disclosed herein.
Claims
1. It is a device, A flow cell having one or more channels, each channel having a first channel opening and a second channel opening, wherein the first channel opening is positioned at a first end of the flow cell and the second channel opening is positioned at a second end of the flow cell, A gasket assembly coupled to each second channel opening, wherein each gasket assembly is Adhesive stack and A gasket assembly comprising a gasket, the gasket having an adhesive stack comprising a first side joined to the gasket and a second side joined to the flow cell.
2. The apparatus according to claim 1, wherein the adhesive stack has through holes, and the gasket has through holes that are aligned with the through holes of the adhesive stack to allow fluid communication through the gasket assembly.
3. The apparatus according to claim 1, wherein the adhesive stack comprises a first adhesive bonded to the flow cell and a second adhesive bonded to the gasket and positioned between the first adhesive and the gasket.
4. The apparatus according to claim 3, wherein each gasket assembly further comprises a separation layer positioned between the first adhesive and the second adhesive, the first adhesive bonding to both the flow cell and the separation layer, and the second adhesive bonding to both the separation layer and the gasket.
5. The apparatus according to claim 4, wherein the separation layer contains polyethylene terephthalate.
6. The apparatus according to claim 4, wherein the separation layer has through holes, the gasket has through holes aligned with the through holes of the separation layer, the first adhesive coats the first side of the separation layer, and the second adhesive coats the second side of the separation layer.
7. The apparatus according to claim 3, wherein the first adhesive comprises an acrylic adhesive and the second adhesive comprises a silicone adhesive.
8. The apparatus according to claim 1, wherein the gasket comprises a silicone elastomer and the flow cell comprises a plurality of channels.
9. The apparatus according to claim 1, further comprising a flow cell manifold coupled to the first end of the flow cell, the manifold including a flow cell manifold inlet, a plurality of fluid lines, and a plurality of flow cell manifold outlets fluidly coupled to the flow cell manifold inlet by corresponding fluid lines, each of the flow cell manifold outlets being coupled to a corresponding first channel opening of the flow cell.
10. The apparatus according to claim 9, further comprising a manifold gasket assembly coupled to the inlet of the flow cell manifold.
11. The apparatus according to claim 9, wherein the manifold gasket assembly comprises a first adhesive bonded to the flow cell manifold, a gasket, and a second adhesive bonded to the gasket and positioned between the first adhesive and the gasket.
12. The apparatus according to claim 9, wherein the flow cell manifold comprises a laminate.
13. It is a device, The aforementioned adhesive stack is The first adhesive and A separation layer having a first side and a second side, which are at least partially covered by the first adhesive, A second adhesive that covers at least partially the second side of the separation layer, wherein the separation layer is positioned between the first adhesive and the second adhesive, The apparatus according to claim 1, wherein the gasket is bonded to the second adhesive, and the second adhesive is positioned between the separation layer and the gasket.
14. The apparatus according to claim 13, further comprising a plurality of gasket assemblies, each of which is spaced apart and bonded to a release liner, and the plurality of gasket assemblies bonded to the release liner form a roll.
15. The system further includes a flow cell interface, The apparatus according to claim 1, wherein the flow cell interface is engageable with a corresponding gasket to establish a fluid coupling between the system and the flow cell.
16. The apparatus according to claim 15, wherein the flow cell interface comprises a plurality of plungers that can engage with the corresponding gasket.
17. The apparatus according to claim 16, further comprising a spring that biases the corresponding plunger.
18. The apparatus according to claim 16, wherein the flow cell interface comprises a plunger guide having a plunger bore in which the corresponding plunger is positioned.
19. The apparatus according to claim 15, wherein the system further comprises a vacuum chuck supporting the flow cell, the vacuum chuck supporting a substantial length of the flow cell between the first end and the second end.
20. The apparatus according to claim 15, further comprising a flow cell frame to which the flow cell and the plurality of gasket assemblies are coupled.