Gasket assembly and related systems and methods
By using an adhesive-backed gasket assembly, the problem of excessive sealing force between the flow cell and the system was solved, resulting in a reduction in the size and complexity of the flow cell and improved optical and thermal interface performance.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- ILLUMINA INC
- Filing Date
- 2022-01-20
- Publication Date
- 2026-05-08
AI Technical Summary
In the prior art, the fluid connection between the flow cell and the system has excessive sealing force, which increases the size and complexity of the flow cell shell and may affect the flatness and optical performance of the flow cell.
An adhesive-backed gasket assembly, comprising an adhesive laminate and a gasket, reduces sealing force and the force required for fluid connection by combining the adhesive laminate with the flow pool and the gasket, and uses a release layer to achieve fluid communication.
It reduces the sealing force between the flow cell and the system, lowers the risk of flow cell warpage, improves optical and thermal interface performance, and reduces the size and complexity of the flow cell housing.
Smart Images

Figure CN115867627B_ABST
Abstract
Description
[0001] Related patent applications
[0002] This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 170,946, filed April 5, 2021, and U.S. Provisional Patent Application No. 63 / 199,916, filed February 2, 2021, the contents of each of which are incorporated herein by reference in their entirety and for all purposes. Background Technology
[0003] The sequencing platform may include a fluid interface that can form a fluid connection with the flow cell. Summary of the Invention
[0004] By providing gasket assemblies and related systems and methods, advantages relative to the prior art and benefits described later in this disclosure can be achieved. Various specific embodiments of the apparatus and methods are described below, and these apparatus and methods (including and excluding the additional specific embodiments listed below) in any combination (provided that such combinations are not inconsistent) can overcome these disadvantages and achieve the beneficial effects described herein.
[0005] According to a first embodiment, an apparatus includes a flow-through pool. The flow-through pool has one or more channels. Each channel has a first channel opening and a second channel opening. The first channel opening is located at a first end of the flow-through pool, and the second channel opening is located at a second end of the flow-through pool. A gasket assembly is coupled to each second channel opening. Each gasket assembly includes an adhesive laminate and a gasket. The adhesive laminate includes a first side bonded to the gasket and a second side bonded to the flow-through pool.
[0006] According to a second embodiment, an apparatus includes a gasket assembly comprising a gasket and an adhesive stack comprising a first adhesive, a release layer, and a second adhesive. The release layer has a second side and a first side at least partially covered by the first adhesive. The second adhesive at least partially covers the second side of the release layer. The release 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 release layer and the gasket. The apparatus also includes a release substrate to which the first adhesive of the adhesive stack is peelably bonded.
[0007] According to a third embodiment, an 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 a first end of the flow cell, and the second channel opening is located at a second end of the flow cell. Gasket assemblies are coupled to each second channel opening. Each gasket assembly includes an adhesive laminate and a gasket. The adhesive laminate includes a first side bonded to the gasket and a second side bonded to the flow cell. The flow cell interface is engageable with a corresponding gasket to establish a fluid connection between the system and the flow cell.
[0008] According to a fourth embodiment, a method includes picking up a gasket assembly using the head of a pick-and-place machine. The gasket assembly includes an adhesive laminate and a gasket. The adhesive laminate includes a second side and a first side bonded to the gasket. The method includes placing the second side of the gasket assembly onto a surface of an opening surrounding a channel in a flow cell.
[0009] According to a fifth embodiment, an apparatus includes a flow cell having a channel including a channel opening and a gasket assembly coupled to the channel opening. The gasket assembly includes an adhesive laminate and a gasket. The adhesive laminate includes a first side bonded to the gasket and a second side bonded to the flow cell.
[0010] According to a sixth embodiment, an apparatus includes an adhesive backing gasket.
[0011] According to a seventh embodiment, a method includes picking up an adhesive-backed gasket and placing the adhesive-backed gasket on a flow-through tank. The method further includes pressing the adhesive-backed gasket into the flow-through tank, thereby attaching the adhesive-backed gasket to the flow-through tank.
[0012] Further according to the aforementioned first, second, third, fourth, fifth, sixth, and / or seventh embodiments, the equipment and / or method may also include any one or more of the following:
[0013] In one embodiment, the adhesive stack has through holes, and the gasket has through holes aligned with the through holes of the adhesive stack to enable fluid communication through the gasket assembly.
[0014] In another embodiment, the adhesive stack includes a first adhesive coupled to a flow cell and a second adhesive coupled to a gasket and positioned between the first adhesive and the gasket.
[0015] In another embodiment, each gasket assembly further includes a release layer positioned between a first adhesive and a second adhesive. The first adhesive is bonded to both the flow pool and the release layer, and the second adhesive is bonded to both the release layer and the gasket.
[0016] In another specific embodiment, the separation layer comprises polyethylene terephthalate.
[0017] In another embodiment, the release layer includes a through-hole, and the gasket has a through-hole aligned with the through-hole of the release layer. A first adhesive is applied to a first side of the release layer, and a second adhesive is applied to a second side of the release layer.
[0018] In another specific embodiment, the first adhesive includes an acrylic adhesive.
[0019] In another specific embodiment, the second adhesive includes a silicone adhesive.
[0020] In another specific embodiment, the gasket comprises a silicone elastomer.
[0021] In another embodiment, the device includes a flow-through manifold connected to a first end of a flow-through pool and including a flow-through manifold inlet, a plurality of fluid lines, and a plurality of flow-through manifold outlets fluidly connected to the flow-through manifold inlet via corresponding fluid lines. Each of the flow-through manifold outlets is connected to a corresponding first channel opening of the flow-through pool.
[0022] In another embodiment, the device includes a manifold gasket assembly connected to the inlet of the flow cell manifold.
[0023] In another embodiment, the manifold gasket assembly includes a first adhesive coupled to a flow cell manifold, a gasket, and a second adhesive coupled to the gasket and positioned between the first adhesive and the second adhesive.
[0024] In another specific implementation, the flow pool manifold includes laminated materials.
[0025] In another embodiment, the device includes a substrate assembly comprising a release substrate, a permanent adhesive, and a foil layer, wherein the permanent adhesive bonds the foil layer and the release layer.
[0026] In another embodiment, the substrate assembly further includes a third adhesive and a polyethylene terephthalate (PET) layer. The third adhesive bonds the foil layer and the PET layer.
[0027] In another embodiment, the device includes multiple gasket assemblies. Each gasket assembly is spaced apart and coupled to a release substrate.
[0028] In another specific implementation, multiple gasket assemblies are attached to a release substrate and form a roller.
[0029] In another embodiment, the flow pool interface includes multiple plungers that can engage with corresponding gaskets.
[0030] In another embodiment, the device includes a spring that biases the corresponding plunger.
[0031] In another embodiment, the flow cell interface includes a plunger guide with a plunger orifice therein for positioning a corresponding plunger.
[0032] In another specific implementation, the system also includes a vacuum chuck that supports the flow cell.
[0033] In another specific implementation, the vacuum chuck supports the flow cell for a basic length between the first and second ends.
[0034] In another embodiment, the device includes a flow cell frame, a flow cell, and a plurality of gasket assemblies connected to the flow cell frame.
[0035] In another embodiment, the method includes pressing a gasket assembly toward the surface of the flow cell, thereby attaching a second side of the adhesive stack to the surface of the flow cell.
[0036] In another specific implementation, the method includes dispensing a washer assembly from a roller comprising a plurality of washer assemblies.
[0037] In another specific implementation, dispensing the washer assembly from the roller includes passing the washer assembly through a guide.
[0038] In another specific implementation, the method includes using a sensor to detect the position of the gasket assembly before picking it up.
[0039] In another embodiment, the adhesive stack includes a first adhesive on a first side of the adhesive stack, a second adhesive on a second side of the adhesive stack, and a release layer positioned between the first adhesive and the second adhesive.
[0040] In another embodiment, the first adhesive comprises an acrylic adhesive, the second adhesive comprises a silicone adhesive, and the release layer comprises a polyethylene terephthalate layer.
[0041] In another specific embodiment, the gasket comprises a silicone elastomer.
[0042] In another specific embodiment, the adhesive-backed gasket includes an adhesive laminate.
[0043] In another specific embodiment, the adhesive laminate comprises polyethylene terephthalate between an acrylic adhesive and a silicone adhesive.
[0044] In another specific implementation, the silicone adhesive is adjacent to the gasket.
[0045] In another specific embodiment, the gasket comprises a silicone elastomer.
[0046] In another embodiment, the device also includes a flow-through tank. An adhesive-backed gasket is attached to the flow-through tank.
[0047] In another embodiment, the apparatus also includes a laminated article and a flow-through tank. The laminated article is coupled to the flow-through tank, and a gasket is coupled to the laminated article.
[0048] In another specific implementation, the circulation pool includes multiple channels.
[0049] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (assuming that such concepts do not contradict each other) are contemplated as part of the subject matter disclosed herein and / or can be combined to achieve specific beneficial effects in particular aspects. Specifically, all combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as part of the subject matter disclosed herein. Attached Figure Description
[0050] Figure 1 A schematic diagram illustrating a specific implementation of the system based on the teachings of this disclosure is shown.
[0051] Figure 2 yes Figure 1 A detailed cross-sectional view of an exemplary embodiment of the flow cell interface, the first portion of the flow cell interface, and the vacuum chuck and flow cell housing assembly, showing... Figure 1 The first end of the flow pool.
[0052] Figure 3 yes Figure 1 A detailed cross-sectional view of the second part of the flow cell interface and an exemplary specific embodiment of the vacuum chuck and flow cell cartridge assembly, showing... Figure 1 The second end of the flow pool.
[0053] Figure 4 yes Figure 1 An isometric view of an exemplary embodiment of the flow pool box assembly.
[0054] Figure 5 yes Figure 4 Bottom plan view of the flow cell box assembly.
[0055] Figure 6 yes Figure 1 An extended isometric view of an exemplary embodiment of a gasket assembly, including adhesive stacks and gaskets, each defining a corresponding through-hole.
[0056] Figure 7 yes Figure 1 An extended isometric view of an exemplary embodiment of the gasket assembly, showing the gasket, first adhesive, second adhesive, and release layer.
[0057] Figure 8 It shows that it can be used with Figure 1 A floor plan of another specific implementation of the circulation pool used in the system.
[0058] Figure 9 It is a system that can be used to assemble flow cells based on the teachings of this disclosure.
[0059] Figure 10 It shows that it can be used with Figure 9 An isometric view of the head used in the system.
[0060] Figure 11 Is it possible to... Figure 9 A cross-sectional view of a portion of the roller in a gasket assembly used in the system.
[0061] Figure 12 It shows the use of Figure 9 System assembly Figure 1 A flowchart of a flow pool box component or any flow pool method disclosed herein. Detailed Implementation
[0062] Although the following text discloses a detailed description of specific embodiments of the methods, apparatus, and / or articles, it should be understood that the legal scope of the property rights is defined by the wording of the claims set forth at the end of this patent. Therefore, the following detailed description should be understood as merely illustrative and does not describe every possible embodiment, as describing every possible embodiment would be impractical, if not impossible. Many alternative embodiments may be implemented using current technology or technology developed after the filing date of this patent. It is contemplated that such alternative embodiments will still fall within the scope of the claims.
[0063] This disclosure relates to a flow cell cartridge assembly including a flow cell with 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 channels of the flow cell. To facilitate fluid connection between the channels and an associated system for, for example, performing analysis on a sample of interest, a gasket may be provided at the outlet of the channel. The gasket may span the width of the flow cell and have an orifice corresponding to the outlet of each channel. While a single gasket is effective in establishing a sealed connection between the flow cell and the associated system, when the flow cell includes multiple channels (e.g., eight channels), the alignment stack between the gasket and the outlets of the channels can be made explicit. Although the foregoing examples refer to flow cells including multiple channels, a flow cell according to the teachings of this disclosure may include a single channel.
[0064] At least one aspect of this disclosure relates to flow cell housing assemblies and related systems that allow for reduced manufacturing tolerances and also reduce the amount of force that may be involved in establishing a fluid connection between the flow cell and the system. In some embodiments, a force of about 1.2 Newtons (N) or less can be used to establish a fluid connection between the system and the flow cell. For example, compared to other methods such as gaskets connected by a bracket, the gaskets and related methods disclosed herein can provide approximately 30% reduction in sealing force, thereby significantly reducing the size and complexity of the flow cell housing. Lower sealing force can also result in less flow cell warping, leading to improved optical and thermal interfaces. Therefore, the disclosed embodiments reduce the likelihood of a lack of fluid connection between the flow cell and the system and also reduce the likelihood that the engagement between the flow cell and the system will adversely affect the flatness of the flow cell.
[0065] Using the disclosed specific embodiments, a reduction in common pipeline volume is also possible compared to gasket-supported connections. Adhesive-backed gaskets, as disclosed herein, also allow for smaller tolerance stack-ups in port alignment and fewer moving parts. The gaskets and related methods of use and manufacture also provide benefits and advantages related to flexible design to accommodate a variety of flow cell configurations.
[0066] The disclosed flow cell assembly includes an adhesive-backed gasket that is respectively adhered to each outlet of a corresponding channel and to the inlet of a flow cell manifold. Alternatively, the flow cell manifold may be omitted, and the adhesive-backed gasket may be attached to the inlet of the corresponding channel. The adhesive-backed gasket may include an adhesive laminate and a gasket, wherein the adhesive laminate has a first side bonded to the gasket and a second side bonded to the flow cell.
[0067] The adhesive stack may include 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. Including two adhesives allows the adhesive-backed gasket to adhere to both the flow cell, which is made of glass, and the gasket, which is made of silicone elastomer. The adhesive stack may also include a release layer positioned between the first adhesive and the second adhesive. The first adhesive may bond to both the flow cell and the release layer, and the second adhesive may bond to both the release layer and the gasket. In some embodiments, the first adhesive is an acrylic adhesive, the second adhesive is a silicone adhesive, and the release layer comprises polyethylene terephthalate (PET). However, other types of adhesives or release layers may be used.
[0068] In some implementations, the gaskets can be positioned on the tape roll, allowing them to be fed into a precision pick-and-place (PNP) machine using a label feeder concept. This could involve feeding the gaskets onto a non-stick surface of the label feeder, allowing the head of the vacuum nozzle to pick them up and place them onto a flow-through pool for automated assembly.
[0069] At least some of the example gaskets and methods of using / applying gaskets to flow cells described herein contribute to a significant reduction in manifold sealing forces, thereby reducing the complexity and / or cost of flow cell retainer architectures. Pick-and-place machines can be used for assembly, i.e., for applying adhesive-backed gaskets to flow cells or for supporting or fluidly connecting laminated structures to flow cells. In some examples, pick-and-place machines are used to pick up gaskets from a label feeder and then align and place the gaskets on / around orifices in the flow cell, where the orifices act as ports providing fluid access to the flow channels of the flow cell.
[0070] Figure 1 A schematic diagram of a specific implementation of system 100 according to the teachings of this disclosure is shown. System 100 can be used to perform analysis on one or more samples of interest. Samples may include one or more DNA clusters that have been linearized to form single-stranded DNA (sstDNA). In the specific implementation shown, system 100 is adapted to receive a flow cell cartridge assembly 102 including a flow cell 103 and a sample cartridge 104, and partially includes a suction 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. Controller 114 is electrically and / or communicatively coupled to drive assembly 112 and imaging system 116, and is adapted to cause drive assembly 112 and / or imaging system 116 to perform the various functions disclosed herein.
[0071] System 100 includes a flow cell housing 122 for receiving a flow cell housing assembly 102, a vacuum chuck 124 for supporting a flow cell 103, and a flow cell interface 126 for establishing a fluid connection between system 100 and flow cell 103. Flow cell interface 126 may include one or more manifolds.
[0072] Referring first to flow-through pool 103, in the illustrated embodiment, flow-through pool 103 includes a plurality of channels 128, each channel having a first channel opening 130 located at a first end 132 of flow-through pool 103 and a second channel opening 134 located at a second end 135 of flow-through pool 103. Depending on the flow direction through the channels 128, either channel opening 130 or 134 can serve as an inlet or outlet. Although flow-through pool 103 is in Figure 1 The diagram is shown as including two channels 128, but may include any number of channels 128 (e.g., 1, 2, 6, 8) (see [reference]). Figure 5 and Figure 8 ).
[0073] The flow cell assembly 102 also includes a flow cell frame 136, a flow cell manifold 137 coupled to a first end 132 of the flow cell 103, and a plurality of gasket assemblies 138 coupled to corresponding second channel openings 134. As used herein, a "flow cell" (also referred to as a flow cell) may include a device having a cap extending over a reaction structure to form flow channels therebetween communicating with a plurality of reaction sites of the reaction structure. Some flow cells may also include a detection device that detects 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 to or otherwise carried by the flow cell frame 136. Although the flow cell frame 136 is shown with Figure 1 The flow cell housing assembly 102 is included together, but the flow cell frame 136 can be omitted. Therefore, the flow cell 103 and the associated gasket assembly 138 can be used with the system 100 without the flow cell frame 136.
[0074] In the specific embodiment shown, the flow cell manifold 137 may be a laminated product and includes a single inlet 140 and multiple outlets 142, each of which is connected to multiple fluid lines 144 (the fluid lines 144 are in...). Figure 5 (As shown more clearly in the diagram) is connected to inlet 140. One of the gasket assemblies 138 is also connected to inlet 140 of flow cell manifold 137. Outlet 142 of flow cell manifold 137 is aligned with and positioned adjacent to first channel opening 130. Therefore, fluid can flow between outlet 142 of flow cell manifold 137 and first channel opening 130 of channel 128. Although Figure 1 The flow cell assembly 102 is shown to include a flow cell manifold 137, but in other embodiments, the flow cell manifold 137 may be omitted. When the flow cell manifold 137 is omitted, the gasket assembly 138 may be connected at the first channel opening 130 in a manner similar to the connection between the gasket assembly 138 at the second channel opening 134 and the flow cell 103.
[0075] Referring to gasket assembly 138, in the illustrated embodiment, 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 the gasket 148 form an adhesive-backed gasket with an annular shape, and the adhesive stack 146 may be formed from 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 bonds. For example, covalent bonds may be formed by activating the glass of the flow cell 103 and activating the second side 152 of the adhesive stack 146 made of silicone, and placing the flow cell 103 and the second side 152 of the adhesive stack 146 into contact with each other. The glass of the flow cell 103 and / or the second side 152 of the adhesive stack 146 may be activated by changing the surface energy of the materials to favor certain properties, such as hydrophobicity, reactivity, adhesion, and / or morphology. Heat and / or pressure may also be used, or alternatively, to activate the second side 152 of the glass and / or adhesive stack 146 of the flow cell 103.
[0076] During operation, the flow cell interface 126 engages with the corresponding gasket 148 to establish a fluid connection 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.
[0077] Referring again to gasket assembly 138, adhesive stack 146 and gasket 148 have through holes 154, 156 aligned with each other to allow fluid communication through gasket assembly 138. Thus, fluid can flow into and / or out of flow reservoir 103 through gasket assembly 138. In the illustrated embodiment, adhesive stack 146 includes a first adhesive 158 coupled to flow reservoir 103 and a second adhesive 160 coupled to gasket 148 and positioned between the first adhesive 158 and gasket 148. Adhesive stack 146 also includes a release layer 162 positioned between the first adhesive 158 and the second adhesive 160. The first adhesive 158 is bonded to both flow reservoir 103 and release layer 162, and the second adhesive 160 is bonded to both release layer 162 and gasket 148.
[0078] To allow fluid to pass through the gasket assembly 138, the release layer 162 defines a through-hole 154 aligned with a through-hole 156 in the gasket 148. In the illustrated embodiment, a first adhesive 158 is applied to a first side 166 of the release layer 162, and a second adhesive 160 is applied to a second side 168 of the release layer 162. The first adhesive 158 and / or the second adhesive 160 may be fully applied, partially applied, or patterned on the release layer 162.
[0079] The first adhesive 158 may be an acrylic adhesive, the second adhesive 160 may be a silicone adhesive, the release layer 162 may comprise polyethylene terephthalate (PET), and the gasket 148 may be a silicone elastomer. The gasket 148 may comprise or otherwise consist of a silicon wafer, Dynaflex... ™ G7702 (TPE), platinum-cured silicone, Santoprene 8281-35 (TPV), thermoplastic elastomers, polypropylene-based polymers, synthetic rubbers, thermoplastic vulcanizates, etc., can be used to form gaskets. However, different adhesives may be used for the first and / or second adhesives 158, 160, and / or different elastomers may be used for gaskets 148. For example, the first adhesive 158 connecting gasket assembly 138 to flow cell manifold 137 may be bonded to flow cell manifold 137 made of PET, while the first adhesive 158 connecting gasket assembly 138 to flow cell 103 may be bonded to flow cell 103 made of glass. However, flow cell manifold 137 and / or flow cell 103 may be made of materials different from those mentioned, including flow cell manifold 137 and / or flow cell 103 being made of the same material.
[0080] Referring now to sample cartridge 104, sample loading manifold assembly 108, and pump manifold assembly 110, in the illustrated embodiment, system 100 includes a sample cartridge container 170 that receives sample cartridge 104 carrying one or more samples of interest (e.g., analytes). System 100 also includes a sample cartridge interface 172 that establishes a fluid connection with sample cartridge 104.
[0081] 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 buffer 180. One or more of the valves 174, 178 can be implemented as rotary valves, pinch valves, level valves, solenoid valves, check valves, piezoelectric valves, and / or three-way valves. However, different types of fluid control devices can be used. One or more of the pumps 176 can be implemented as syringe pumps, peristaltic pumps, and / or diaphragm pumps. However, other types of fluid delivery devices can be used. The buffer 180 may be a serpentine buffer and may be, for example... Figure 1 The system 100 temporarily stores one or more reactive components during bypass operation. Although cache 180 is shown as being included in pump manifold assembly 110, in another embodiment, cache 180 may be located in a different location. For example, cache 180 may be included in sampling manifold assembly 106 or in another manifold downstream of bypass fluid line 182.
[0082] The sample loading manifold assembly 108 and pump manifold assembly 110 allow one or more samples of interest to flow from sample cassette 104 to flow cell cassette assembly 102 via fluid lines 184. In some embodiments, the sample loading manifold assembly 108 can individually load / address each channel 128 of flow cell 103 with a sample of interest. The process of loading channel 128 with a sample of interest can be described using... Figure 1 The system 100 occurs automatically.
[0083] like Figure 1 As shown in system 100, sample cartridge 104 and sample loading manifold assembly 108 are located downstream of flow cell cartridge assembly 102. Therefore, sample loading manifold assembly 108 can load the sample of interest into flow cell 103 from the rear of flow cell 103. Loading the sample of interest from the rear of flow cell 103 can be referred to as "post-loading". Post-loading the sample of interest into flow cell 103 reduces contamination. In the illustrated embodiment, sample loading manifold assembly 108 is coupled between flow cell cartridge assembly 102 and pump manifold assembly 110.
[0084] To draw a sample of interest from sample cartridge 104 toward pump manifold assembly 110, sample valve 174, pump valve 178, and / or pump 176 may be selectively actuated to push the sample of interest toward pump manifold assembly 110. Sample cartridge 104 may include multiple sample reservoirs that are selectively fluid-accessible via corresponding sample valves 174. Thus, each sample reservoir can be selectively isolated from other sample reservoirs using corresponding sample valves 174.
[0085] To direct the sample of interest toward the corresponding channel 128 of the flow cell 103 and away from the pump manifold assembly 110, the sample valve 174, pump valve 178, and / or pump 176 can be selectively actuated to push the sample of interest toward the flow cell assembly 102 and into the corresponding channel 128 of the flow cell 103. In some embodiments, each channel 128 of the flow cell 103 receives the sample of interest. In other embodiments, one or more channels 128 selectively receive the sample of interest, and other channels 128 do not receive the sample of interest. For example, a channel 128 of the flow cell 103 that may not receive the sample of interest could alternatively receive a washing buffer.
[0086] The drive assembly 112 interfaces with the sample manifold assembly 106 and the pump manifold assembly 110 to allow flow of one or more reagents interacting with the sample within the flow cell 103. In one embodiment, a reversible terminator is attached to the reagent to allow the incorporation of a single nucleotide into a growing DNA strand. In some such embodiments, one or more nucleotides have a unique fluorescent label that emits a color when excited. The color (or the absence of color) is used to detect the corresponding nucleotide. In the illustrated embodiment, the imaging system 116 excites one or more 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 light, and the image data may include one or more colors emitted by the corresponding labels 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. The solid-state imaging device may include a charge-coupled device (CCD) and / or a complementary metal-oxide-semiconductor (CMOS).
[0087] After acquiring image data, drive assembly 112 interfaces with suction manifold assembly 106 and pump manifold assembly 110 to allow another reaction component (e.g., reagent) to flow through flow cell 103. This reaction component is then received by waste reservoir 118 via main waste fluid line 186 and / or otherwise depleted by system 100. Some of the reaction components undergo a flushing operation, which chemically cleaves the fluorescently labeled and reversible terminator from the sstDNA. The sstDNA is then prepared for another cycle.
[0088] The main waste fluid line 186 connects the pump manifold assembly 110 to the waste reservoir 118. In some embodiments, the pump 176 and / or pump valve 178 of the pump manifold assembly 110 selectively allow the reaction components to flow from the flow cell assembly 102 through the fluid line 184 and the sample loading manifold assembly 108 to the main waste fluid line 186.
[0089] Flow cell assembly 102 is connected to central valve 188 via flow cell interface 126. Auxiliary waste fluid line 190 is connected to central valve 188 and waste reservoir 118. In some embodiments, auxiliary waste fluid line 190 receives excess fluid of the sample of interest from flow cell assembly 102 via central valve 188 and allows excess fluid of the sample of interest to flow to waste reservoir 118 when the sample of interest is post-loaded into flow cell 103, as described herein. That is, the sample of interest can be loaded from the rear of flow cell 103, and any excess fluid of the sample of interest can exit from the front of flow cell 103. By post-loading the sample of interest into flow cell 103, different samples can be loaded into corresponding channels 128, and a single flow cell manifold 137 can connect the front of flow cell 103 to central valve 188 to direct excess fluid of each sample of interest to auxiliary waste fluid line 190. Once the sample of interest is loaded into flow cell 103, flow cell manifold 137 can be used to deliver commonly used reagents from the front (e.g., upstream) of flow cell 103 to each channel 128, with the reagents exiting from the rear (e.g., downstream) of flow cell 103. In other words, the sample of interest and the reagents can flow in opposite directions through the channels 128 of flow cell 103.
[0090] Referring to the sample suction manifold assembly 106 shown in the specific embodiment, the sample suction 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 selection valve. The central valve 188 and the valves 192, 194 of the sample suction manifold assembly 106 can be selectively actuated to control the flow of fluid through fluid lines 196, 198, 200. One or more of valves 192, 194 can be implemented by rotary valves, pinch valves, level valves, solenoid valves, check valves, piezoelectric valves, etc. Other fluid control devices may be suitable.
[0091] The sampling manifold assembly 106 can be coupled to a corresponding number of reagent reservoirs 202 via reagent pipettes 204. The reagent reservoirs 202 may contain fluids (e.g., reagents and / or another reaction component). In some embodiments, the sampling manifold assembly 106 includes multiple ports. Each port of the sampling manifold assembly 106 can receive one of the reagent pipettes 204. The reagent pipettes 204 may be referred to as fluid lines.
[0092] The shared line valve 192 of the aspiration manifold assembly 106 is connected to the central valve 188 via the shared reagent fluid line 196. Different reagents can flow through the shared reagent fluid line 196 at different times. In one embodiment, when a flushing operation is performed before changing between one reagent and another, the pump manifold assembly 110 can aspirate a cleaning buffer through the shared reagent fluid line 196, the central valve 188, and the flow cell assembly 102. Therefore, the shared reagent fluid line 196 can participate 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.
[0093] A bypass valve 194 of the aspiration manifold assembly 106 is connected to a 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. Fluids that can flow through the dedicated reagent fluid lines 198, 200 may be used during sequencing operations, and these fluids may include lysis reagents, incorporation reagents, scan reagents, lysis washing buffer, and / or washing buffer. Therefore, when a flushing operation is performed in association with the bypass valve 194 before changing between one reagent, the aspiration manifold assembly 106 can aspirate washing buffer through the central valve 188 and / or the flow cell assembly 102. However, because only a single reagent can flow through each dedicated reagent fluid line 198, 200, the dedicated reagent fluid lines 198, 200 themselves may not be flushed. When system 100 uses reagents that may have adverse reactions with other reagents, including dedicated reagent fluid lines 198, 200 may be advantageous. Furthermore, reducing the number or length of fluid lines flushed when changing between different reagents reduces reagent consumption and flushing volume, and can reduce the cycle time of system 100. Although two dedicated reagent fluid lines 198, 200 are shown, any number of dedicated fluid lines may be included in system 100.
[0094] Bypass valve 194 is also connected to cache 180 of pump manifold assembly 110 via bypass fluid line 182. One or more reagent perfusion, hydration, mixing, and / or delivery operations can be performed using bypass fluid line 182. Perfusion, hydration, mixing, and / or delivery operations can be performed independently of flow cell assembly 102. Therefore, operations using bypass fluid line 182 can occur, for example, during the incubation of one or more samples of interest within flow cell assembly 102. That is, shared line valve 192 can be used independently of bypass valve 194, such that bypass valve 194 can utilize bypass fluid line 182 and / or cache 180 to perform one or more operations while shared line valve 192 and / or central valve 188 simultaneously, substantially simultaneously, or offset synchronously perform other operations. Therefore, system 100 can perform multiple operations simultaneously, thereby reducing runtime.
[0095] Referring now to drive assembly 112, in the illustrated embodiment, drive assembly 112 includes a pump drive assembly 206 and a valve drive assembly 208. Pump drive assembly 206 may be adapted to interface with one or more pumps 176 to pump fluid through flow cell 103 and / or load one or more samples of interest into flow cell 103. 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.
[0096] Referring to controller 114, in the illustrated embodiment, controller 114 includes a user interface 210, a communication interface 212, one or more processors 214, and a memory 216 storing instructions executable by the one or more processors 214 to perform various functions, including those disclosed in the illustrated embodiment. The user interface 210, communication interface 212, and memory 216 are electrically and / or communicatively coupled to the one or more processors 214.
[0097] In a specific implementation, the user interface 210 is adapted to receive input from the user and provide the user with information related to the operation and / or analysis performed by the system 100. 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).
[0098] In a specific implementation, communication interface 212 is adapted to enable communication between system 100 and a remote system (e.g., a computer) via a network. The network may 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, near field communication (NFC) connection, etc. Some communications provided to the remote system may be associated with analysis results, imaging data, etc., generated by system 100 or otherwise obtained. Some communications provided to system 100 may be associated with fluid analysis operations, patient records, and / or protocols to be executed by system 100.
[0099] One or more processors 214 and / or system 100 may include one or more of a processor-based system or a microprocessor-based system. In some embodiments, one or more processors 214 and / or system 100 include one or more of a programmable processor, programmable controller, microprocessor, microcontroller, graphics processing unit (GPU), digital signal processor (DSP), reduced instruction set computer (RISC), application-specific integrated circuit (ASIC), field-programmable gate array (FPGA), field-programmable logic device (FPLD), logic circuitry, and / or another logic-based device that performs various functions, including those described herein.
[0100] The memory 216 may include one or more of the following: semiconductor memory, magnetically readable memory, optical memory, hard disk drive (HDD), optical storage drive, solid-state storage device, solid-state drive (SSD), 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) memory, optical disc (CD), optical disc read-only memory (CD-ROM), digital versatile optical disc (DVD), Blu-ray disc, redundant array of independent disks (RAID) system, cache, and / or any other storage device or storage disk in which information is stored for any duration (e.g., permanently, temporarily, long time period, for buffering, for caching).
[0101] Figure 2 yes Figure 1 A detailed cross-sectional view of an exemplary embodiment of the flow cell interface 126, first portion 250, vacuum chuck 124, and flow cell housing assembly 102, showing... Figure 1 The first end 132 of the flow cell 103. 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 same flow cell box assembly 102.
[0102] In the illustrated embodiment, the first portion 250 of the flow-through interface 126 includes a plunger guide 252 comprising a plunger bore 254 in which a plunger 256 is positioned. A spring 258 is shown positioned to bias the corresponding plunger 256 in a direction generally indicated by arrow 260 and engage it with a corresponding washer assembly 138. The plunger 256 defines a fluid path 262 through which fluid is allowed to pass. Also as Figure 2 As shown, the vacuum chuck 124 supports the basic width 266 of the flow cell 103. Additionally, the vacuum chuck 124 can support the basic length or the entire length of the flow cell 103 between the ends 132 and 135.
[0103] Figure 3 yes Figure 1 A detailed cross-sectional view of an exemplary embodiment of the flow cell interface 126, second portion 268, and vacuum chuck 124 and flow cell housing assembly 102, showing... Figure 1 The second end 135 of the flow cell 103. 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.
[0104] In the specific embodiment shown, the second portion 268 of the flow pool interface 126 includes a plunger guide 252 with a plunger hole 254 in which a corresponding plunger 256 is positioned. A spring 258 is positioned to bias the corresponding plunger 256 in a direction generally indicated by arrow 260 and engage it with the corresponding washer assembly 138.
[0105] Figure 4 yes Figure 1 An isometric view of an exemplary embodiment of the flow cell box assembly 102. In the illustrated embodiment, the flow cell box assembly 102 includes a flow cell frame 136, a flow cell 103 having multiple channels 128, a flow cell manifold 137, and a gasket assembly 138. The flow cell box assembly 102 also includes a radio frequency identification (RFID) tag 270 for tracking and / or identification purposes, and multiple retaining clips 272 for securing the flow cell 103, the flow cell manifold 137, and / or the RFID tag 270 within or relative to the flow cell frame 136.
[0106] Referring to flow cell frame 136, in the illustrated embodiment, flow cell frame 136 has a peripheral wall 274 and a top surface 276. The peripheral wall 274 and top surface 276 define a cavity 278. Cavity 278 includes an upper opening 280 and a lower opening 282. The upper opening 280 is defined by the top surface 276 and allows image data of flow cell 103 to be acquired using imaging system 116. The lower opening 282 is defined by the lower edge 284 of the peripheral wall 274 and allows samples of interest to be loaded into channels 128 of flow cell 103 via different gasket assemblies 138.
[0107] Figure 5 yes Figure 4 The figure shows a bottom plan view of the flow cell assembly 102. 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 outlet in the outlet 142 via the fluid line 144. The flow cell manifold 137 and its fluid line 144 allow for fewer valves to be used to control fluid flow through the flow cell assembly 102.
[0108] Figure 6 yes Figure 1 The image shows an expanded isometric view of an exemplary embodiment of a gasket assembly 138, comprising an adhesive stack 146 defining one of corresponding through-holes 154 and 156, and a gasket 148. The gasket 148 may be formed from a silicon wafer, and the adhesive stack 146 may be a tape and / or transfer adhesive double-coated with PET. Typically, the gasket assembly 138 may include a heat-stable adhesive, and the gasket material may be able to withstand multiple thermal cycles between approximately 20°C and approximately 60°C, and has a shelf life of approximately 18 months for the material.
[0109] To form the adhesive stack 146 and / or gasket 148, laser cutting, die-cutting, knife / flash cutting, and / or waterjet cutting processes can be used to cut the adhesive stack 146 and / or gasket 148. These or other processes allow the gasket 148 to be formed with fewer defects and with no or no knitting defects.
[0110] Figure 7 yes Figure 1An expanded isometric view of an exemplary embodiment of gasket assembly 138 shows gasket 148, first adhesive 158, second adhesive 160, and release layer 162. In some embodiments, gasket assembly 138 has a diameter of approximately 4 mm + / - 0.2 mm, through-holes 154 and / or 156 have a diameter of approximately 1 mm + / - 0.1 mm, gasket 148 has a thickness of approximately 1.0 mm + / - 0.1 mm, gasket 148 has a hardness of approximately 30 Shore A + / - 5 Shore A, and adhesive stack 146 has a thickness of approximately 75 micrometers (µm). While thickness and / or diameter are mentioned in association with gasket assembly 138 and / or its components 148, 154, 156, 158, 160, 162, other dimensions and / or diameters may be suitable.
[0111] Figure 8 It shows that it can be used with Figure 1 A plan view of another specific implementation of the circulation pool 103 used in system 100. Figure 4 On the contrary in its specific implementation Figure 8 The flow pool 103 includes two channels 128 and has a small width. Although the gasket assembly 138 is not shown for connection to... Figure 8 The flow pool 103, but the gasket assembly 138 can be connected in a similar manner to how the gasket assembly 138 is connected. Figure 4 The flow pool 103 is included in a manner that, while two channels 128 are shown, may include any number of channels, such as, for example, six channels or one channel. If the flow pool 103 includes one channel, the flow pool manifold 137 may be omitted.
[0112] Figure 9 This is a system 300 that can be used to assemble a flow cell 103 according to the teachings of this disclosure. In the illustrated embodiment, system 100 includes a pick-and-place machine 302, a gasket feeder 304, and a carrier 306 that receives 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 for picking up and placing gasket assemblies 138 and a sensor 310 for obtaining position data. The position data may include the position of the assembled gasket assembly 138 and / or the flow cell 103 and may be used to identify the flow cell reference, the flow cell manifold reference, and / or the gasket assembly 138 reference by optical inspection or other processes.
[0113] The head 308 of the pick-and-place machine 302 defines a recess 311 for receiving the end portion 312 of the washer assembly 138 and includes a pair of arcuate orifices 313 that allow a connection to be formed between the head 308 and the washer assembly 138. The washer feeder 304 has a spool 314 for receiving a roller 315 that includes the washer assembly 138 on a belt 316. The belt 316 may be a low-tack belt and may be referred to as a substrate assembly. The washer feeder 304 also includes a guide 318 that guides the belt 316 when the washer assembly 138 is dispensed during the assembly process, and a sensor 320 that senses when the washer assembly 138 is located at a pick-up position 322 on the washer feeder 304. In response to the sensor 320 sensing the washer assembly 138 at the pickup position 322, the washer feeder 304 may stop feeding the washer assembly 138 until, for example, the washer assembly 138 at the pickup position 322 is picked up by the head 308.
[0114] In operation, the pick-and-place machine 302 acquires position data from sensors 310 and / or 320, and based on the position data, the pick-and-place machine 302 causes the head 308 to pick up one or more gasket assemblies 138 from the belt 316 and align the gasket assembly 138 with one of the second channel openings 134 of the channel 128 of the flow reservoir 103. Once aligned, the head 308 moves to attach the gasket assembly 138 to the flow reservoir 103 at the corresponding second channel opening 134 by pressing the gasket assembly 138 into engagement with the flow reservoir 103. The pick-and-place machine 302 may repeat the process of attaching the gasket assembly 138 to the flow reservoir 103 until each of the second channel openings 134 has one of the gasket assemblies 138 attached to its adjacent side. The pick-and-place machine 302 may also attach the flow reservoir manifold 137 and the associated gasket assembly 138 to the first end 132 of the flow reservoir 103 in a similar manner. In a specific implementation that omits the flow cell manifold 137, the pick-and-place machine 302 can connect the corresponding gasket assembly 138 to each of the first channel openings 130 in a manner similar to how the gasket assembly 138 is connected at the second channel opening 134.
[0115] The flow cell assembly, including the flow cell 103 and associated components 137, 138, can then be unloaded from the carrier 306 and / or from the system 100. Quality control procedures can be performed on the flow cell 103, including, for example, scanning the flow cell 103 and / or pressure testing the flow cell 103 to verify fluid integrity. A barcode label can be affixed to the flow cell 103. After performing the quality tests, the flow cell assembly can be secured within the flow cell frame 136.
[0116] Figure 10 It shows that it can be used with Figure 9An isometric view of a head 308 used with system 100. In the specific embodiment shown, head 308 includes an end portion 324 that includes an arcuate aperture 313 and a recess 311 of the end portion 312 of receiving washer assembly 138. The arcuate aperture 313 may extend through the length of head 308 or a portion of the length of head 308.
[0117] Figure 11 Is it possible to... Figure 9 A cross-sectional view of a portion of a roller 315 of a gasket assembly 138 used with system 100. In the illustrated embodiment, roller 315 includes a gasket assembly 138 and a belt 316 to which the gasket assembly 138 is removably coupled. Belt 316 includes a release substrate 352, a permanent adhesive 354, and a foil layer 356. The permanent adhesive 354 can bond the foil layer 356 and the release substrate 352 and ensure that the release substrate 352 does not detach from the gasket assembly 138 when the gasket assembly 138 is removed. The foil layer 356 can be used to stop the laser from cutting through the entire belt 316 during a laser cutting process, thereby leaving the gasket assembly 138 on the release substrate 352 for easy removal.
[0118] In some embodiments, dry ice cleaning can be used to remove debris. The belt 316 also includes a third adhesive 358 and a PET layer 360. The third adhesive 358 bonds the foil layer 356 to the PET layer 360, and the PET layer 360 prevents the foil layer 356 from wrinkling. In other embodiments, the third adhesive 358 may be a barrier coating, and the PET layer 360 may be a heat-sealing coating. A substrate 362 may also be disposed on the gasket assembly 138 to prevent the gasket assembly 138 from attaching to another layer of the belt 316 on the roller 315. To use as... Figure 11 The single-row washer assembly 138 shown generates a roller 315, which can be cut into a larger roller having multiple rows (e.g., four rows) of washer assemblies 138 using a slitting machine.
[0119] Figure 12 It shows the use of Figure 9 System 300 Assembly Figure 1 The flowchart is a part of the flow pool box component 102 or any flow pool 103 method disclosed herein. The execution order of the boxes may be changed, and / or some of the boxes described may be changed, eliminated, combined and / or subdivided into multiple boxes.
[0120] Process 1200 begins by dispensing the washer assemblies 138 from a roller 315 comprising a plurality of washer assemblies 138 (box 1202). Dispensing the washer assemblies 138 from the roller 315 may include a guide 318 for guiding the washer assemblies 138 through a washer feeder 304. The position of the washer assemblies 138 is detected using a sensor 320 (box 1204). The position of the washer assemblies 138 may be associated with the washer assemblies 138 being located at a pick-up position 322. The washer assemblies 138 are picked up using a head 308 of a pick-and-place machine 302 (box 1206). The washer assembly 138 includes an adhesive stack 146 and a washer 148. The adhesive stack 146 has a first side 150 bonded to the washer 148 and includes a first adhesive 158 on the first side 150 of the adhesive stack 146, a second adhesive 160 on a second side 152 of the adhesive stack 146, and a release layer 162 positioned between the first adhesive 158 and the second adhesive 160. In some embodiments, the first adhesive 158 comprises an acrylic adhesive, the second adhesive 160 comprises a silicone adhesive, and the release layer 162 comprises a polyethylene terephthalate layer.
[0121] The second side 152 of the gasket assembly 138 is placed on the surface of the openings 130, 134 of the channel 128 surrounding the flow pool 103 (frame 1208), and the gasket assembly 138 is pressed toward the surface of the flow pool 103, thereby attaching the second side 152 of the adhesive stack 146 to the surface of the flow pool 103 (frame 1210).
[0122] The above description is provided to enable those skilled in the art to practice the various configurations described herein. Although the subject matter has been specifically described with reference to various accompanying drawings and configurations, it should be understood that these drawings and configurations are for illustrative purposes only and should not be considered as limiting the scope of the subject matter.
[0123] As used herein, an element or step described in the singular and preceded by the words "an" or "a" should be understood to not exclude multiple said elements or steps unless such exclusion is expressly indicated. Furthermore, the reference to "an embodiment" is not intended to be interpreted as excluding the existence of additional embodiments that also include the described features. Moreover, unless expressly stated to the contrary, an embodiment that "comprises" or "has" one or more elements having a particular attribute may include additional elements, whether or not they have that attribute. Furthermore, the terms "comprises," "has," etc., are used interchangeably herein.
[0124] The terms “substantially,” “about,” and “approximately” used throughout this specification are used to describe and indicate small fluctuations, such as small fluctuations due to variations in the process. For example, they may refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%.
[0125] Many other ways may exist to implement the subject matter. The various functions and elements described herein may be distinguished differently from those shown without departing from the scope of the subject matter. Various modifications to these specific embodiments will be readily apparent to those skilled in the art, and the general principles defined herein can be applied to other specific embodiments. Therefore, those skilled in the art can make many changes and modifications to the subject matter without departing from its scope. For example, different numbers of given modules or units may be used, one or more different types of given modules or units may be used, given modules or units may be added, or given modules or units may be omitted.
[0126] Underlined and / or italicized headings and subheadings are used for convenience only, do not limit the scope of the subject matter, and are not incorporated into the explanation of the description of the subject matter. All structural and functional equivalents of elements throughout the various specific embodiments described herein, known or later to those skilled in the art, are expressly incorporated herein by reference and are intended to be covered by the subject matter. Furthermore, nothing disclosed herein is intended to be exclusive to the public, regardless of whether such disclosure is expressly set forth in the foregoing description.
[0127] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (assuming that such concepts do not contradict each other) are contemplated as part of the subject matter disclosed herein. Specifically, all combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as part of the subject matter disclosed herein.
Claims
1. An apparatus, said apparatus comprising: A flow cell comprising means having a cap extending over a reaction structure to form one or more channels therebetween, each channel communicating with a plurality of reaction sites of the reaction structure, wherein the flow cell has one or more channels, each channel having a first channel opening and a second channel opening, the first channel opening being positioned at a first end of the flow cell and the second channel opening being positioned at a second end of the flow cell. and Gasket assemblies, connected at each second channel opening and configured to establish a fluid connection between the flow cell and a system outside the flow cell, each gasket assembly comprising: Adhesive lamination; and A gasket, the adhesive stack comprising a first side bonded to the gasket and a second side bonded to the flow reservoir; wherein the adhesive stack comprises a first adhesive bonded to the flow reservoir and a second adhesive bonded to the gasket and positioned between the first adhesive and the gasket, wherein each gasket assembly further comprises a release layer positioned between the first adhesive and the second adhesive, the first adhesive being bonded to both the flow reservoir and the release layer and the second adhesive being bonded to both the release layer and the gasket.
2. The device of claim 1, wherein the adhesive stack has a through-hole and the gasket has a through-hole, the through-hole of the gasket being aligned with the through-hole of the adhesive stack to achieve fluid communication through the gasket assembly.
3. The apparatus of claim 1, wherein the separation layer comprises polyethylene terephthalate.
4. The device of claim 1, wherein the separating layer includes a through hole and the gasket has a through hole aligned with the through hole of the separating layer, and wherein the first adhesive is applied to a first side of the separating layer and the second adhesive is applied to a second side of the separating layer.
5. The device of claim 1, wherein the first adhesive comprises an acrylic adhesive.
6. The device of claim 1, wherein the second adhesive comprises a silicone adhesive.
7. The device according to any one of claims 1 to 2, wherein the gasket comprises a silicone elastomer.
8. The apparatus according to any one of claims 1 to 2, further comprising a flow-through manifold connected to the first end of the flow-through pool and including a flow-through manifold inlet, a plurality of fluid lines and a plurality of flow-through manifold outlets fluidly connected to the flow-through manifold inlet via corresponding fluid lines, each of the flow-through manifold outlets being connected to a corresponding first channel opening of the flow-through pool.
9. The apparatus of claim 8, further comprising a manifold gasket assembly connected to the inlet of the flow cell manifold.
10. The device of claim 9, wherein the manifold gasket assembly comprises a first adhesive coupled to the flow cell manifold, a gasket, and a second adhesive coupled to the gasket and positioned between the first adhesive and the gasket.
11. The apparatus of claim 8, wherein the flow cell manifold comprises a laminate.
12. The device according to any one of claims 1 to 2, wherein the flow pool comprises a plurality of the channels.
13. An apparatus comprising: The system includes a flow pool interface; A flow cell includes means having a cap extending over a reaction structure to form one or more channels therebetween, each channel communicating with a plurality of reaction sites of the reaction structure, wherein each channel has a first channel opening and a second channel opening, the first channel opening being located at a first end of the flow cell and the second channel opening being located at a second end of the flow cell. and Washer assemblies, each washer assembly being connected to each second channel opening, each washer assembly comprising: Adhesive lamination; and A gasket, the adhesive stack comprising a first side bonded to the gasket and a second side bonded to the flow reservoir, wherein the adhesive stack comprises a first adhesive bonded to the flow reservoir and a second adhesive bonded to the gasket and positioned between the first adhesive and the gasket, wherein each gasket assembly further comprises a release layer positioned between the first adhesive and the second adhesive, the first adhesive being bonded to both the flow reservoir and the release layer and the second adhesive being bonded to both the release layer and the gasket; The flow cell interface is capable of engaging with a corresponding gasket to establish a fluid connection between the system and the flow cell.
14. The device of claim 13, wherein the flow pool interface comprises a plurality of plungers capable of engaging the corresponding gasket.
15. The device of claim 14, further comprising a spring biasing the corresponding plunger.
16. The device according to any one of claims 14 to 15, wherein the flow pool interface includes a plunger guide, the plunger guide including a plunger orifice in which the corresponding plunger is positioned.
17. The apparatus according to any one of claims 13 to 15, wherein the system further comprises a vacuum chuck supporting the flow cell.
18. The apparatus of claim 17, wherein the vacuum chuck supports the flow cell for a basic length between the first end and the second end.
19. The device according to any one of claims 13 to 15, the device further comprising a flow cell frame, the flow cell and a plurality of gasket assemblies being coupled to the flow cell frame.
20. A method of manufacturing the device according to claim 1, the method comprising: The head of the pick-and-place machine is used to pick up a washer assembly, the washer assembly including an adhesive stack and a washer, the adhesive stack including a second side and a first side bonded to the washer; 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 release layer positioned between the first adhesive and the second adhesive; as well as Place the second side of the gasket assembly onto the surface of the opening of the channel surrounding the flow pool.
21. The method of claim 20, further comprising pressing the gasket assembly toward the surface of the flow cell to attach the second side of the adhesive stack to the surface of the flow cell.
22. The method of any one of claims 20 to 21, further comprising dispensing the washer assemblies from a roller comprising a plurality of the washer assemblies.
23. The method of claim 22, wherein dispensing the washer assembly from the roller comprises passing the washer assembly through a guide.
24. The method of claim 22, further comprising detecting the position of the gasket assembly using a sensor before picking up the gasket assembly.
25. The method of claim 20, wherein the first adhesive comprises an acrylic adhesive, the second adhesive comprises a silicone adhesive, and the release layer comprises a polyethylene terephthalate layer.
26. The method of claim 20, wherein the gasket comprises a silicone elastomer.
27. An apparatus comprising: A flow cell comprising means having a cap extending over a reaction structure to form a channel therebetween, the channel communicating with a plurality of reaction sites of the reaction structure, wherein the channel includes a channel opening; and Gasket assembly, connected at the channel opening and configured to establish a fluid connection between the flow cell and a system outside the flow cell, the gasket assembly comprising: Adhesive lamination; and The gasket, the adhesive stack including a first side bonded to the gasket and a second side bonded to the flow reservoir, wherein the adhesive stack includes a first adhesive bonded to the flow reservoir and a second adhesive bonded to the gasket and positioned between the first adhesive and the gasket, wherein each gasket assembly further includes a release layer positioned between the first adhesive and the second adhesive, the first adhesive being bonded to both the flow reservoir and the release layer and the second adhesive being bonded to both the release layer and the gasket.
Citation Information
Patent Citations
Sample collection and transfer device
CN106536057A
Automated point-of-care devices for complex sample processing and methods of use thereof
CN110226089A
Self-adhesive reinforced foam gasket
US6190751B1
Surface mount technology compatible EMI gasket and a method of installing an EMI gasket on a ground trace
US6255581B1