Apparatus and method for reducing oxidation of reagents in reagent cartridges

Abstract

Apparatus and method for reducing oxidation of reagents in a reagent cartridge are disclosed. According to one embodiment, the apparatus includes a reagent cartridge having a plurality of side walls and end walls forming wells. Reagents are placed in the wells, and a float lid is placed on the upper surface of the reagents in the wells. The float lid covers most of the upper surface of the reagents.

Description

Technical Field

[0001] Related Applications This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 456,074, filed Mar. 31, 2023, the entire content of which is incorporated herein by reference for all purposes.

Background Art

[0002] Reducing or preventing the oxidation of reagents stored / transported within a reagent cartridge and delivered from the reagent cartridge can be difficult. In many processes, the reagents are stored / transported within a reagent cartridge having a cover or a sealing foil positioned to cover the wells containing the reagents and delivered from the reagent cartridge in order to reduce or prevent oxidation of the reagents with the cartridge.

Summary of the Invention

[0003] Advantages and benefits beyond the prior art as described hereinafter in this disclosure can be achieved through the provision of an apparatus, a reagent cartridge, and a method for reducing the oxidation of reagents within a reagent cartridge. Various embodiments of the apparatus, the reagent cartridge, and the method are described below, and an apparatus, a reagent cartridge, and a method including the additional embodiments listed below in any combination (provided these combinations are not inconsistent) and an apparatus, a reagent cartridge, and a method excluding the same can overcome these drawbacks and achieve the benefits described herein.

[0004] According to a first embodiment, the apparatus comprises a reagent cartridge having a plurality of sidewalls and endwalls forming wells. Reagents are disposed within the wells, and a floating lid is disposed over the upper surface of the reagents within the wells. The floating lid covers most of the upper surface of the reagents.

[0005] According to a second embodiment, the apparatus includes a reagent cartridge having a plurality of side walls and end walls forming wells. Reagents are placed in the wells, and a plurality of plastic pellets are placed on the upper surface of the reagents in the wells. The plurality of plastic pellets cover most of the upper surface of the reagents.

[0006] According to a third embodiment, the apparatus comprises a reagent cartridge having a plurality of side walls and end walls forming wells. Reagents are placed in the wells, and oil is placed on the upper surface of the reagents in the wells. The oil covers the upper surface of the reagents.

[0007] According to a fourth embodiment, the reagent cartridge comprises a body having an end wall and a plurality of side walls extending from the end wall, the end wall and the plurality of side walls forming a plurality of wells. An opening extends through the end wall into one of the plurality of wells. A floating cap is disposed in one of the plurality of wells, and a cover is placed on the body and covers at least a portion of the plurality of wells.

[0008] According to a fifth embodiment, the method includes filling at least a portion of the wells of a reagent cartridge with a reagent, wherein the reagent cartridge comprises a plurality of side walls and end walls forming a well, and positioning a float lid on the upper surface of the reagent in the well such that the float lid covers most of the upper surface of the reagent.

[0009] According to the sixth embodiment, the apparatus includes a body and a lid. The body includes a plurality of side walls and a bottom surface that form a reagent reservoir. The bottom surface includes a port. The lid is movably disposed within the reagent reservoir and includes a projection extending toward the bottom surface. The projection engages with the bottom surface to prevent the lid from obstructing the flow of fluid through the port.

[0010] According to the seventh embodiment, the apparatus includes a body and a lid. The body includes a plurality of side walls and a bottom surface that form a reagent reservoir. The lid is movably disposed within the reagent reservoir.

[0011] According to the eighth embodiment, a nucleic acid sequencing method using the apparatus of any of embodiments 1 to 4 or 6 to 7 includes taking a first portion of the reagent from the well at a first time, and taking a second portion of the reagent from the well at a second time, which is at least 36 hours after the first time, without any reduction in reagent chemistry.

[0012] According to the ninth embodiment, the apparatus includes a reagent cartridge comprising a well, a reagent disposed within the well, and a cover disposed within the well.

[0013] Furthermore, according to the aforementioned first, second, third, fourth, fifth, sixth, seventh, eighth, and / or ninth embodiments, the apparatus, reagent cartridge, and / or method may further include or comprise one or more of the following:

[0014] In one embodiment, the upper surface of the floating lid is convex.

[0015] According to another embodiment, the float cover comprises a plurality of first projections positioned around the outer circumference of the float cover and extending from the bottom surface of the float cover.

[0016] According to another embodiment, the float cover comprises a plurality of second projections positioned around the outer circumference of the float cover and extending from the upper surface of the float cover.

[0017] In another embodiment, the first set of protrusions are axially aligned with the second set of protrusions.

[0018] In another embodiment, the float lid includes at least one opening formed through the float lid and configured to receive at least one of a sipper, a wash tube, and / or an additional reagent container.

[0019] In another embodiment, the device comprises a support column having an outer shape, the support column being configured to be arranged with a well so as to be substantially parallel to the side wall. The floating lid includes a guide opening having a shape substantially the same as the outer shape of the support column. The floating lid is disposed in the well with the support column extending through the guide opening.

[0020] In another embodiment, the device comprises a support disposed at an end of the support column, the support having at least two legs extending towards and to each side wall respectively.

[0021] In another embodiment, the support column and the support form an integral one-piece unit.

[0022] In another embodiment, each of the plurality of plastic pellets has at least one of a cuboid shape, an oval shape, a cylindrical shape, or an ellipsoid of revolution shape.

[0023] In another embodiment, each of the plurality of plastic pellets has a maximum axial length of about 3.0 to about 4.0 mm.

[0024] In another embodiment, each of the plurality of plastic pellets has a maximum axial length of less than about 1.5 mm.

[0025] In another embodiment, the oil is one of mineral oil or silicone oil.

[0026] In another embodiment, the method includes arranging a support column having an outer shape in a well substantially parallel to the side wall, and arranging a floating lid in the well such that the support column extends through a guide opening in the floating lid.

[0027] In another embodiment, the device includes a reagent disposed in a reagent reservoir.

[0028] In another embodiment, the reagent includes a liquid reagent.

[0029] In another embodiment, the reagent includes a dry reagent.

[0030] In another embodiment, each of the protrusions has an outward-facing surface that engages or interacts with the sidewall.

[0031] In another embodiment, the outward-facing surface corresponds to the sidewall.

[0032] In another embodiment, the outward-facing surface has a flat portion.

[0033] In another embodiment, the lid includes a second protrusion that extends away from the bottom surface.

[0034] In another embodiment, each of the second protrusions has an outward-facing surface that engages the sidewall.

[0035] In another embodiment, the interaction between the second protrusion and the sidewall prevents the lid from rotating within the reagent reservoir.

[0036] In another embodiment, the lengths of the protrusion and the second protrusion are similar or the same.

[0037] In another embodiment, the length of the protrusion is shorter than the length of the second protrusion.

[0038] In another embodiment, one or more of the protrusion or the second protrusion has a semi-circular cross-section.

[0039] [[ID= In another embodiment, the reagent reservoir has an opening and further includes a liquid-impermeable barrier that covers the opening of the reagent reservoir.<00001s124>

[0040] In another embodiment, the liquid-impermeable barrier comprises a foil or a thin plastic sheet. <s

[0041] In another embodiment, the device includes a cover that covers the liquid-impermeable barrier and is coupled to the body.

[0042] In another embodiment, the cover includes an opening that allows access to a liquid-impermeable barrier through the opening.

[0043] In another embodiment, the lid is intended to allow temperature control of the reagents in the reagent reservoir.

[0044] In another embodiment, the second time is at least 10 days after the first time.

[0045] In another embodiment, the second time is at least 15 days after the first time.

[0046] In another embodiment, the cover includes a floating lid positioned over the upper surface of the reagent in the well, the floating lid covering most of the upper surface of the reagent.

[0047] In another embodiment, the cover contains oil disposed on the upper surface of the reagent in the well, and the oil covers the upper surface of the reagent.

[0048] In another embodiment, the cover includes a plurality of plastic pellets arranged on the upper surface of the reagent in the well, the plurality of plastic pellets covering most of the upper surface of the reagent.

[0049] In another embodiment, the cover includes a plurality of pellets arranged on the upper surface of the reagent in the well, the plurality of pellets covering most of the upper surface of the reagent.

[0050] 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]

[0051] [Figure 1]A perspective view of a first embodiment of a device for reducing the oxidation of reagents in a reagent cartridge is shown. [Figure 2] Figure 1 shows a perspective view of the device with the cover removed. [Figure 3] The cross-sectional view of the apparatus in Figure 1 is shown along line AA in Figure 1. [Figure 4] Figure 1 shows a perspective view of the floating cover of the device. [Figure 5] A perspective view of a second embodiment of a device for reducing the oxidation of reagents in a reagent cartridge is shown. [Figure 6] Figure 5 shows a cross-sectional view of the apparatus along line BB. [Figure 7] Figure 5 shows a perspective view of the floating cover, support column, and support structure of the device. [Figure 8] A perspective view of a third embodiment of a device for reducing the oxidation of reagents in a reagent cartridge is shown. [Figure 9] Figure 8 shows a cross-sectional view of the apparatus along line CC. [Figure 10] The cross-sectional view of the apparatus in Figure 8 is shown along line DD in Figure 8. [Figure 11] Figure 8 shows a perspective view of the floating cover of the device. [Figure 12] A perspective view of a fourth embodiment of a device for reducing the oxidation of reagents in a reagent cartridge is shown. [Figure 13] Figure 12 shows a perspective view of the device with the cover removed. [Figure 14] Figure 12 shows a top perspective view of the floating cover of the device. [Figure 15] Figure 12 shows a perspective view of the bottom of the floating cover of the device. [Figure 16] A perspective view of a fifth embodiment of a device for reducing the oxidation of reagents in a reagent cartridge is shown. [Figure 17] Figure 16 shows a perspective view of the device with the cover removed. [Figure 18] Figure 16 shows a cross-sectional view of the apparatus along line EE. [Figure 19]A perspective view of a sixth embodiment of a device for reducing the oxidation of reagents in a reagent cartridge is shown. [Figure 20] Figure 19 shows a perspective view of the device with the cover removed. [Figure 21] Figure 19 shows a cross-sectional view of the apparatus along line FF. [Figure 22] A first embodiment of a method for reducing the oxidation of reagents in a reagent cartridge is shown. [Figure 23] A schematic diagram of one embodiment of the system as taught in this disclosure is shown. [Modes for carrying out the invention]

[0052] The following text discloses a detailed description of embodiments of a 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 embodiments, as it would be impractical, if not impossible, to describe all possible embodiments. Numerous alternative embodiments can be implemented using either the current art or art developed after the filing date of this patent. Such alternative embodiments are expected to still fall within the scope of the claims.

[0053] In many processes, reagents are stored / transported in reagent cartridges that have covers or sealed foils positioned over the wells containing the reagents to reduce or prevent oxidation of the reagents by the cartridge, and are delivered from there. However, the ability to reduce or prevent the oxidation of the reagents is significantly reduced if the cover is removed, if the cover does not provide a sufficient airtight seal, if oxygen is present in the wells when the cover is applied, or after the sealed foil has been punctured.

[0054] Generally, the rate of oxygen diffusion into a reagent is proportional to the percentage of oxygen in the headspace above the reagent in the well, the exposed surface area of ​​the reagent, and the diffusion coefficients of oxygen and the reagent.

[0055] At least one aspect of this disclosure relates to an apparatus, reagent cartridge, and method for reducing the oxidation of a reagent in a reagent cartridge. In at least one aspect of this disclosure, one or more engineering control agents (such as a float, plastic pellets, or oil) are added to the reagent well on the top surface of the reagent so as to cover most of the reagent. These engineering control agents reduce the rate of oxygen diffusion from the headspace in the well into the reagent by reducing the surface area of ​​the reagent exposed to oxygen.

[0056] Figures 1 to 4 show a first embodiment of a device 100 that can be used to reduce the oxidation of reagents in a reagent cartridge. In this embodiment, the device 100 includes a reagent cartridge 102 having a main body 104 having an end wall 108 or bottom and a plurality of side walls 106 extending from the end wall 108. The side walls 106 and end wall 108 of the main body 104 can form a well 112 or a plurality of wells, depending on the design and use of the reagent cartridge 102. Reagents 114 can be placed in the wells 112, and an opening 110 can be formed in the end wall 108, providing fluid communication with the wells 112 and extending through the end wall 108 into the wells 112 to extract the reagents 114 from the wells 112 during operation. The opening 110 may be referred to as a port. The reagents 114 may be liquid reagents or dry reagents. Alternatively, the reagents 114 may be omitted from the wells 112 and / or added later. To reduce oxidation of reagent 114 and, in some cases, to assist in temperature control of reagent 114, a floating lid 120 may be placed in the well 112 on the upper surface 116 of reagent 114. For example, the floating lid 120 may allow reagent 114 to remain at a threshold temperature.

[0057] The floating lid 120 can be made from any suitable material, such as polypropylene, such that the floating lid 120 floats on the upper surface 116 of the reagent 114, covers most of the upper surface 116 of the reagent 114, and reduces the gap formed between the edge of the floating lid 120 and the side wall 106. The cover 118 can also be placed on the main body 104 so as to cover at least some of the wells, and in some embodiments all of the wells.

[0058] The upper surface 124 of the floating lid 120 may have a convex, arc-shaped surface. This allows the reagent 114 to be added to the well 112 while the floating lid 120 is already positioned in the well 112. Once the reagent is added to the well 112, it flows down from the convex upper surface 124 of the floating lid 120 toward the outer periphery 122, passing through the gap formed between the outer periphery 122 and the side wall 106 into the well 112. The outer periphery 122 may be referred to as the periphery, outer boundary, and / or outer surface. The outer periphery 122 may have any contour including one or more straight surfaces and / or one or more curved surfaces, and / or form any shape having any number of sides. The reagent may be added to the well 112 additionally or alternatively through the opening 110.

[0059] As is most commonly seen in Figure 4, the float cover 120 may have a first set of projections 128 positioned around its outer circumference 122 and extending downward from its bottom surface 126. The first set of projections 128 can be used to prevent the float cover 120 from tilting and thus getting stuck in the well 112, and when the level of reagent 114 is low, the float cover 120 can contact the end wall 108 and prevent it from getting stuck. The projections 128 can engage with the end wall 108, separating the float cover 120 from the opening 110 and preventing the float cover 120 from obstructing the fluid flow through the opening 112. The float cover 120 may also include a second set of projections 130, which may be located at the same positions around the outer circumference 122 as the first set of projections 128, axially aligned with the first set of projections 128, or at other positions around the outer circumference 122, and may extend upward from the upper surface 124 of the float cover 120 opposite the first set of projections 128. The second set of projections 130 may also, individually or together with the first set of projections 128, prevent the float cover 120 from tilting and getting caught in the well 112. The eight pairs of projections 128, 130 are aligned to engage and / or interact with different parts and / or surfaces of the well 112. Alternatively, any other number of projections 128 and / or 130 may be included, for example, based on the shape of the well 112. Alternatively, instead of individual protrusions, the first plurality of protrusions 128 and / or the second plurality of protrusions 130 can each be peripheral walls extending from the upper surface 124 and / or bottom surface 126 of the floating cover 120.

[0060] Figures 5 to 7 show a second embodiment of the apparatus 200 that can be used to reduce the oxidation of reagents in a reagent cartridge. In this embodiment, the apparatus 200 includes a reagent cartridge 202 having a main body 204 having an end wall 208 or bottom and a plurality of side walls 206 extending from the end wall 208. The side walls 206 and end wall 208 of the main body 204 can form a well 212 or a plurality of wells, depending on the design and use of the reagent cartridge 202. Reagents 214 can be placed in the wells 212, and openings 210 can be formed in the end wall 208 to fluidize the wells 212, extending through the end wall 208 into the wells 212 to extract the reagents 214 from the wells 212 during operation. A floating lid 220 can also be placed in the wells 212 on the top surface 216 of the reagents 214 to reduce the oxidation of the reagents 214 and, in some cases, to assist in temperature control of the reagents 214. The floating cover 220 is similar to the floating cover 120 in Figure 1. The floating cover 220 has a different shape corresponding to the well 212 and includes a guide opening 232, as further disclosed below.

[0061] The floating lid 220 can be made from any suitable material, such as polypropylene, such that the floating lid 220 floats on the upper surface 216 of the reagent 214, covering most of the upper surface 216 of the reagent 214, and minimizing the gap formed between the edge of the floating lid 220 and the side wall 206. The cover 218 can also be placed on the main body 204 so as to cover at least some of the wells, and in some embodiments, all of the wells. The cover 218 defines holes that allow perforators of associated instruments, such as the system 2100 in Figure 23, to perforate the liquid impermeable barrier.

[0062] The upper surface 224 of the floating lid 220 can have a convex, arc-shaped surface. This allows the reagent 214 to be added to the well 212 while the floating lid 220 is already placed inside the well 212. When the reagent is added to the well 212, it flows down from the convex upper surface 224 of the floating lid 220 toward the outer circumference 222, passes through the gap formed between the outer circumference 222 and the side wall 206, and enters the well 212.

[0063] As is most commonly seen in Figure 7, the float cover 220 may have a first set of projections 228 positioned around the outer circumference 222 and extending downward from the bottom surface 226 of the float cover 220. The first set of projections 228 can be used to prevent the float cover 220 from tilting and thus getting stuck in the well 212, and can prevent the float cover 220 from contacting the end wall 208 and getting stuck when the level of reagent 214 is low. Although not shown in this embodiment, the float cover 220 may also include a second set of projections, such as the second set of projections 130 described above, which may be positioned axially aligned with the first set of projections 228 and at the same positions around the outer circumference 222, or at other positions around the outer circumference 222 and extending upward from the top surface 224 of the float cover 220 opposite the first set of projections 228. The second set of protrusions can also prevent the floating cover 220 from tilting and getting caught in the well 212, either individually or together with the first set of protrusions 228. Alternatively, instead of individual protrusions, the first set of protrusions 228 and / or the second set of protrusions can each be peripheral walls extending from the upper surface 224 and / or bottom surface 226 of the floating cover 220.

[0064] The device 200 may also include a guide structure that guides the floating cover 220 vertically and helps prevent the floating cover 220 from tilting. Referring to Figures 6 and 7, the device 200 may also include a support column 234 configured to be positioned within the well 212 substantially parallel to the side wall 206. The support column 234 has an external shape (a "cross" or "plus" shape as shown), and the floating cover 220 has a guide opening 232 that is substantially the same as the external shape of the support column 234, but slightly larger. The support column 234 extends through the guide opening 232 within the floating cover 220, and the support column 234 can help guide the floating cover 220 vertically when it is positioned within the well 212. Additionally, to keep the column 234 in a vertical position and parallel to the side walls 206, the support 236 may be positioned at or near the end of the column 234 and may have legs 238 extending outward from the column 234 toward each side wall 206. As shown in Figures 5 to 7, the support 236 has four legs 238, but may have any number of legs 238 desired for a particular application and a particular well shape. Typically, at least two legs 238 oriented in substantially opposite directions should be used to provide support to the column 234. Each leg 238 may also have a support foot 240 positioned at the end of the leg 238, which extends substantially perpendicular to the leg 238 and substantially parallel to each side wall 206 to help support the column 234 and the support 236 between the side walls 206 in the well 212. As shown in the figure, the support column 234 and the support body 236 may be a single, integrated unit in some embodiments, or they may be two separate units that are fixed, connected, or mounted together.

[0065] Figures 8 to 11 show a third embodiment of the apparatus 300 that can be used to reduce oxidation of reagents in a reagent cartridge. In this embodiment, the apparatus 300 includes a reagent cartridge 302 having a main body 304 with an end wall 308 or bottom and a plurality of side walls 306 extending from the end wall 308. The reagent cartridge 302 may be configured to be pressurized so as to allow the reagent contained within the reagent cartridge 302 to be pushed out of the reagent cartridge 302 under positive pressure. The side walls 306 and end wall 308 of the main body 304 can form a well 312 or a plurality of wells, depending on the design and use of the reagent cartridge 302. Reagents 314 can be placed in the wells 312, and an opening 310 can be formed in the end wall 308 to fluidize into the wells 312, extending through the end wall 308 into the wells 312, allowing the reagents 314 to be extracted from the wells 312 during operation. To reduce oxidation of reagent 314 and, in some cases, to assist in temperature control of reagent 314, a floating lid 320 may be placed in the well 312 on the upper surface 316 of reagent 314.

[0066] The floating lid 320 can be made from any suitable material, such as polypropylene, such that the floating lid 320 floats on the upper surface 316 of the reagent 314, covers most of the upper surface 316 of the reagent 314, and minimizes the gap formed between the edge of the floating lid 320 and the side wall 306. The cover 318 can also be placed on the main body 304 so as to cover at least some of the wells, and in some embodiments all of the wells.

[0067] The upper surface 324 of the floating lid 320 may have a convex, arc-shaped surface. This allows the reagent 314 to be added to the well 312 while the floating lid 320 is already positioned within the well 312. Once the reagent is added to the well 312, it flows down from the convex upper surface 324 of the floating lid 320 toward the outer circumference 322, passing through the gap formed between the outer circumference 322 and the side wall 306 into the well 312. Additionally, the floating lid 320 may have any outer circumference shape desired for fitting into a given well. For example, as shown in Figures 9 to 11, the floating lid 320 may have substantially parallel straight sides and tapered ends to fit into the well 312.

[0068] As is most commonly seen in Figure 11, the float lid 320 may have a first set of projections 328 positioned around the outer circumference 322 and extending downward from the bottom surface 326 of the float lid 320. The first set of projections 328 can be used to prevent the float lid 320 from tilting and thus getting stuck in the well 312, and when the level of reagent 314 is low, the float lid 320 can contact the end wall 308 and prevent it from getting stuck. The float lid 320 may also include a second set of projections 330, which may be positioned axially aligned with the first set of projections 328 and at the same positions around the outer circumference 322, or at other positions around the outer circumference 322 and extending upward from the top surface 324 of the float lid 320 opposite the first set of projections 328. The second set of projections 330, individually or together with the first set of projections 328, can also prevent the floating cover 320 from tilting and getting caught in the well 312. Alternatively, instead of individual projections, the first set of projections 328 and / or the second set of projections 330 can each be peripheral walls extending from the upper surface 324 and / or bottom surface 326 of the floating cover 320.

[0069] Figures 12 to 15 show a fourth embodiment of the apparatus 400 that can be used to reduce the oxidation of reagents in a reagent cartridge. In this embodiment, the apparatus 400 includes a reagent cartridge 402 having a main body 404 having an end wall 408 or a bottom and a plurality of side walls 406 extending from the end wall 408. The side walls 406 and end wall 408 of the main body 404 can form a well 412 or a plurality of wells, depending on the design and use of the reagent cartridge 402. Reagents 414 can be placed in the wells 412. A floating lid 420 can also be placed in the wells 412 on the top surface 416 of the reagent 414 to reduce the oxidation of the reagent 414 and, optionally, to assist in temperature control of the reagent 414.

[0070] The floating lid 420 can be made from any suitable material, such as polypropylene, such that the floating lid 420 floats on the upper surface 416 of the reagent 414, covers most of the upper surface 416 of the reagent 414, and minimizes the gap formed between the edge of the floating lid 420 and the side wall 406. The cover 418 can also be placed on the main body 404 so as to cover the well 412, or, if there are multiple wells, at least some of the multiple wells, and in some embodiments all of the multiple wells.

[0071] The upper surface 424 of the floating lid 420 can have a convex, arc-shaped surface. This allows the reagent 414 to be added to the well 412 while the floating lid 420 is already placed inside the well 412. When the reagent 414 is added to the well 412, it flows down from the convex upper surface 424 of the floating lid 420 toward the outer circumference 422, passes through the gap formed between the outer circumference 422 and the side wall 406, and enters the well 412.

[0072] Although not shown in the specific embodiments of Figures 12 to 15, the float lid 420 may have a first plurality of projections similar to the first plurality of projections 128, which are located around the outer circumference 422 and extend downward from the bottom surface 426 of the float lid 420. The first plurality of projections can be used to prevent the float lid 420 from tilting and thus getting stuck in the well 412, and can prevent the float lid 420 from contacting the end wall 408 and getting stuck when the level of reagent 414 is low. The float lid 420 may also include a second plurality of projections similar to the second plurality of projections 130, which are located at the same positions around the outer circumference 422 as the first plurality of projections and axially aligned with the first plurality of projections, or at other positions around the outer circumference 422 and extend upward from the top surface 424 of the float lid 420 opposite the first plurality of projections. The second set of projections, individually or together with the first set of projections, can also prevent the floating cover 420 from tilting and getting caught in the well 412. Alternatively, instead of individual projections, the first set of projections and / or the second set of projections can each be peripheral walls extending from the upper surface 424 and / or bottom surface 426 of the floating cover 420.

[0073] The float lid 420 may also include at least one opening 442 formed through the float lid 420 which can be configured to receive additional structures such as a shipper, a wash tube, and / or additional reagent containers. For example, as shown in Figures 12 to 15, the float lid 420 includes a first opening 442a configured to receive a shipper 444 through it, a second opening 442b configured to receive a wash tube 446 through it, and a third opening 442c configured to receive an additional reagent container 448 through it. As shown in Figure 15, the float lid 420 may also have a cylindrical or partially cylindrical wall 428 that surrounds, or at least partially surrounds, at least one of the openings 442 and extends downward from the bottom surface 426 of the float lid 420. The wall 428 can be used to prevent the floating lid 420 from tilting and thus getting stuck in the well 412, and when the level of reagent 414 is low, the floating lid 420 can come into contact with the end wall 408 and prevent it from getting stuck.

[0074] Figures 16-18 show a fifth embodiment of the apparatus 500 that can be used to reduce the oxidation of reagents in a reagent cartridge. Similar to apparatus 100, in this embodiment the apparatus 500 includes a reagent cartridge 502 having a main body 504 with an end wall 508 or bottom and a plurality of side walls 506 extending from the end wall 508. The side walls 506 and end wall 508 of the main body 504 can form a well 512 or a plurality of wells, depending on the design and use of the reagent cartridge 502. Reagents 514 can be placed in the wells 512, and openings 510 can be formed in the end wall 508 to fluidize the wells 512 and extend through the end wall 508 into the wells 512 to extract the reagents 514 from the wells 512 during operation. To reduce the oxidation of reagents 514, a plurality of pellets, i.e., plastic pellets 550, can also be placed in the wells 512 on the top surface 516 of the reagents 514. In some embodiments, the pellets 550 may be made from any suitable material, e.g., any material compatible with the reagent and having a density less than that of the reagent. One or more layers of the plastic pellets 550 float on the upper surface 516 of the reagent 514, covering most of the upper surface 516 of the reagent 513, each having at least one of the following shapes: cuboid, oval, cylindrical, or ellipsoidal. The use of plastic pellets 550 can provide an oxygen barrier effect of about 65–80%, minimizing the risk of incompatibility with the reagent 514. The plastic pellets 550 may be made from Braskem HDPE, but alternatively, they can be made from any suitable material such as Bormed LDPE, Marlex HDPE, DT3300 PP, or Profax PD702 PP. Therefore, in some embodiments, the pellets 550 may not be made from plastic. Additionally, to provide sufficient coverage of the upper surface 516 of the reagent 512 and reduce the volume of the passages between each plastic pellet, each plastic pellet 550 may have a maximum axial length of about 3.0 mm to about 4.0 mm. Micropellets may also be used if appropriate for a given application, in which case each plastic pellet 550 has a maximum axial length of less than about 1.5 mm.Micropellets occupy a much smaller headspace volume and can provide a higher surface coverage percentage of the reagent 514 (due to reduced gaps between pellets). Covers 518 can also be placed on the main body 504 to cover at least some of the wells, and in some embodiments, all of the wells.

[0075] To avoid contamination of reagent 514, the plastic pellets 550 should be washed before being placed in well 512. This can be done by deionization, washing (e.g., using fluid agitation to remove contaminants and filter them out, such as ultrasonic cleaning using a Jayco Ultrasonic Cleaner, ultrasonic agitation, or continuous filtration of the solvent containing particulate matter using a 5 μm filter), dust removal and washing (e.g., using a Pelletron De-Duster).

[0076] Figures 19 to 21 show a sixth embodiment of the apparatus 600, which can be used to reduce the oxidation of reagents in a reagent cartridge. Similar to apparatus 100, in this embodiment, the apparatus 600 includes a reagent cartridge 602 having a main body 604 having an end wall 608 or bottom and a plurality of side walls 606 extending from the end wall 608. The side walls 606 and end wall 608 of the main body 604 can form a well 612 or a plurality of wells, depending on the design and use of the reagent cartridge 602. Reagents 614 can be placed in the wells 612, and an opening 610 can be formed in the end wall 608 to fluidize the wells 612, extending through the end wall 608 into the wells 612 to extract the reagents 614 from the wells 612 during operation. To reduce the oxidation of reagents 614, oil 655 can also be placed in the wells 612 on the upper surface 616 of the reagents 614. The oil 655 can be mineral oil, silicone oil, or any other type of oil that provides an oxygen barrier and does not react with reagent 614. Using oil 655 on the upper surface 616 of reagent 614 can provide an oxygen barrier effect of more than 85% and uses only a small extra headspace volume for the oil 655. A cover 618 may also be placed on the main body 604 to cover at least some of the wells, and in some embodiments all of the wells.

[0077] Referring to Figure 22, a first embodiment of a method for reducing reagent oxidation is shown using the apparatus shown in Figures 1 to 15 and described above. In this embodiment, a reagent cartridge is provided in block 700, comprising an end wall or bottom and a plurality of side walls extending from the end wall. The end wall and the plurality of side walls form a well. In block 710, at least a portion of the well is filled with reagent. In block 720, a float lid is positioned on the upper surface of the reagent in the well such that the float lid floats on the upper surface of the reagent and covers most of the upper surface of the reagent.

[0078] In some embodiments, the upper surface of the float cap may be convex to allow reagents added to the well after the float cap has been placed in the well to flow away from the float cap and into the well through the gap formed by the edge and side wall of the float cap. In these embodiments, the float cap may be placed in the well before the well is filled with reagents.

[0079] In other embodiments, the float cap may have a plurality of first projections positioned around its outer circumference and extending from its bottom surface to prevent the float cap from tipping over and getting caught in the well and to prevent the float cap from contacting the end wall when the reagent level is low. Where appropriate, the float cap may also have a plurality of second projections positioned around its outer circumference and extending from its top surface, which may be axially aligned with the first plurality of projections.

[0080] In other embodiments, the float lid may have at least one, and possibly more, openings formed through the float lid, which is configured to receive at least one of a sipper, a wash tube, and / or an additional reagent container.

[0081] In other embodiments, the support can be positioned substantially parallel to the side wall together with the well. The support may have an external shape, and the guide opening in the float cover may have a shape substantially the same as, but slightly larger than, the external shape of the support. The float cover can then be positioned in the well such that the support extends through the guide opening in the float cover. The support may also include a support positioned at or near the end of the support, which in some embodiments forms a one-piece unit integral with the support. The support may support the support in the well by having at least two or more legs that extend toward and to each side wall in a direction away from the support.

[0082] Figure 23 shows a schematic diagram of one embodiment of System 2100 as taught in this disclosure. System 2100 can be used to perform analysis on one or more target samples, such as diffusion sequencing. The sample may include one or more DNA clusters linearized to form single-stranded DNA (sstDNA). In the illustrated embodiment, System 2100 receives a reagent cartridge 2102 and also includes, in part, a drive assembly 2104, a controller 2106, an imaging system 2108, and a waste reservoir 2109. Reagent cartridge 2102 may be implemented by any one of reagent cartridges 102, 202, and 502 shown in Figures 1, 5, and 16. In other embodiments, reagent cartridge 2202 may be implemented by any one of reagent cartridges 302 and 402 shown in Figures 8 and 12. However, reagent cartridge 2102 may be implemented in different ways.

[0083] The controller 2106 is electrically and / or communicatively coupled to the drive assembly 2104 and the imaging system 2108, and causes the drive assembly 2104 and / or the imaging system 2108 to perform various functions as disclosed herein. In an alternative embodiment, system 2100 may include a sipper assembly that includes a sipper for drawing reagents from reagent cartridge 2101. System 2100 may include, for example, the sipper assembly when used with reagent cartridge 402 in Figure 12. System 2100 may additionally or alternatively include a gas source and a regulator that can pressurize reagent cartridge 2102 and use positive pressure to push reagents out of reagent cartridge 2102.

[0084] The reagent cartridge 2102 carries the sample to be tested and may be referred to as a consumable. The drive assembly 2104 may interface with the reagent cartridge 2102 to rehydrate dry reagents that interact with the sample through the reagent cartridge 2102 and / or to pass one or more liquid reagents (e.g., A, T, G, C nucleotides).

[0085] In some embodiments, a reversible terminator is attached to the reagent to allow a single nucleotide to be incorporated by the sstDNA in each cycle. In some such embodiments, 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 illustrated embodiment, the imaging system 2108 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 a 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 2100. The imaging system 2108 may be a fluorescence spectrophotometer including an objective lens and / or a solid-phase imaging device. The solid-phase imaging device may include a charge-coupled device (CCD) and / or a complementary metal oxide semiconductor (CMOS).

[0086] After image data is acquired, the drive assembly 2104 interfaces with the reagent cartridge 2102 and flows another reaction component (e.g., a reagent), which is then received by the waste reservoir 2109 and / or discharged by the reagent cartridge 2102 in other ways. The sstDNA is then ready for another cycle.

[0087] Referring to reagent cartridge 2102, in the illustrated embodiment, reagent cartridge 2102 is receivable within a cartridge receptacle 2110 of system 2100 and includes a reagent reservoir 2300, a body 2302, one or more valves 2118, and a fluid line 2120. The valves 2118 may be selectively actuated to control the flow of fluid through the fluid line 2120. One or more of the valves 2118 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezo valves, etc. The body 2302 may be formed from solid plastic using injection molding and / or additive manufacturing techniques. In some embodiments, the reagent reservoir 2114 is formed integrally with the body 2302. In other embodiments, the reagent reservoir 2114 is formed separately and coupled to the body 2302. The reagent reservoir 2114 and / or reagent cartridge 2102 may comprise overmolded Santoprene thermoplastic elastomer (TPE) or polypropylene and / or cyclic olefin copolymer (COC) having another thermoplastic elastomer. Other materials may prove suitable for the reagent reservoir 2114 and / or reagent cartridge 2102.

[0088] The reagent cartridge 2102 is in fluid communication with the flow cell 2142. In the illustrated embodiment, the flow cell 2142 is held by the reagent cartridge 2102 and received via the flow cell receptacle 2147. As used herein, “flow cell” may include a device having a lid that extends above a reaction structure and forms flow channels between which it communicates with a plurality of reaction sites of the reaction structure, and may further include a detection device that detects a specified reaction occurring at or near the reaction site. Alternatively, the flow cell 2142 may be integrated with the reagent cartridge 2102. In such an embodiment, the flow cell receptacle 2147 may not be included, or at least the flow cell 2142 may not be removablely received within the reagent cartridge 2102. As a further alternative, the flow cell 2142 may be separated from the reagent cartridge 2102.

[0089] The reagent cartridge 2102 may include a pump 2156 positioned between the flow cell 2142 and the waste reservoir 2109. The waste reservoir 2109 may be selectively receptacleable within the waste reservoir receptacle 2158 of the system 2100. The pump 2156 may be implemented by a syringe pump, a peristaltic pump, a diaphragm pump, or the like. While the pump 2156 may be positioned between the flow cell 2142 and the waste reservoir 2109, in other embodiments, the pump 2156 may be positioned upstream of the flow cell 2142 or may be omitted entirely.

[0090] The reagent cartridge 2102 includes a body 2302, which includes side walls 2304 and a bottom surface 2306 that form a reagent reservoir 2308. The reagent reservoir 2308 may be referred to as a well. The bottom surface 2306 includes a port 2310. The reagent cartridge 2300 also includes, in the illustrated embodiment, a lid 2312 movably disposed within the reagent reservoir 2308. The lid 2312 may be referred to as a floating lid or cover. The lid 2312 includes a projection 2314 extending toward the bottom surface 2306. The projection 2314 may engage with the bottom surface 2306 to prevent the lid 2312 from obstructing the flow of fluid through the port 2310.

[0091] Each projection 2314 has an outward-facing surface 2318 that engages with or interacts with the side wall 2304. The outward-facing surface 2318 of the projection 2314 may correspond to the side wall 2304. The outward-facing surface 2318 of the projection 2314 may have, for example, a flat portion and / or a contour corresponding to the side wall 2304.

[0092] In this illustrated embodiment, the lid 2312 also includes a second projection 2320 extending away from the bottom surface 2306. The second projection 2320 has a corresponding outward-facing surface 2322 that engages with the side wall 2304. The second projection 2320 may interact with the outward-facing wall to prevent the lid 2312 from rotating within the reagent reservoir 2308. The projection 2314 may also prevent the lid 2312 from rotating within the well. In this illustrated embodiment, the length of the projection 2314 is shown to be shorter than the length of the second projection 2320. The lengths of the projection 2314 and the second projection 2320 may be the same as or identical to those shown in other embodiments disclosed, or the projection 2314 may be longer than the second projection 2320. The projections 2314 and / or the second projections 2320 may be vertical, slightly tapered inward, and / or include rounded or filleted edges. One or more of the projections 2314 or the second projections 2320 may have a semicircular cross-section. However, the projections 2314 and / or the second projections 2320 may have any cross-section. Alternatively, the second projections 2320 may be omitted.

[0093] The reagent cartridge 2300 is shown containing reagent 2324 disposed within the reagent reservoir 2308. Reagent 2324 may be a liquid reagent and / or a dry reagent. Alternatively, reagent 2324 may be omitted. In some embodiments, the lid 2312 may allow temperature control of reagent 2324 in the reagent reservoir 2308. The lid 2312 may be omitted in other examples, and pellets and / or oil may be used instead to reduce the oxidation rate of reagent 2324.

[0094] A liquid-impermeable barrier 2324 covering the opening 2325 of the reagent reservoir 2308 is shown. The liquid-impermeable barrier 2324 may include foil or a thin plastic sheet. For example, the liquid-impermeable barrier 2324 may be implemented by a thin metal foil such as aluminum foil, or a thin plastic sheet such as Saran® wrap.

[0095] A cover 2326 is shown, which covers the liquid-impermeable barrier 2324 and is coupled to the main body 2302. The cover 2326 includes an opening 2328, which allows the liquid-impermeable barrier 2324 to be accessed through the opening 2328.

[0096] Referring here to the drive assembly 2104, in the illustrated embodiment, the drive assembly 2104 includes a pump drive assembly 2160, a valve drive assembly 2162, and an actuator assembly 2164. The pump drive assembly 2160 interfaces with the pump 2156 and pumps fluid through the reagent cartridge 2102, and the valve drive assembly 2162 interfaces with the valve 2118 and controls the position of the valve 2118. The actuator assembly 2164 interfaces with the reagent reservoir 2308 and penetrates the liquid-impermeable barrier 2324. As an example, the actuator assembly 2164 includes a rod 2166 having a distal end 2168 that passes through an opening 2328 and penetrates the liquid-impermeable barrier 2324. The actuator assembly 2164 may include a linear actuator.

[0097] Referring to controller 2106, in the illustrated embodiment, controller 2106 includes a user interface 2174, a communication interface 2176, one or more processors 2178, and a memory 2180 that stores instructions executable by one or more processors 2178 for performing various functions, including those in the disclosed embodiment. The user interface 2174, the communication interface 2176, and the memory 2180 are electrically and / or communicatively coupled to one or more processors 2178.

[0098] In one embodiment, the user interface 2174 receives input from the user and provides the user with information related to the operation of the system 2100 and / or the analysis being performed. The user interface 2174 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).

[0099] In this embodiment, the communication interface 2176 enables communication between the system 2100 and a remote system (e.g., a computer) over a network. The network may include an intranet, a local area network (LAN), a wide area network (WAN), and the like. Some of the communication provided to the remote system may be associated with analysis results, imaging data, etc., created by or otherwise acquired by the system 2100. Some of the communication provided to the system 2100 may be associated with fluid analysis operations, patient records, and / or protocols performed by the system 2100.

[0100] One or more processors 2178 and / or system 2100 may include one or more processor-based systems or microprocessor-based systems. In some embodiments, one or more processors 2178 and / or system 2100 may include a reduced-instruction set computer (RISC), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), a field-programmable logic device (FPLD), a logic circuit, and / or another logic-based device that performs a variety of functions, including those described herein.

[0101] Memory 2180 may include one or more of the following: hard disk drives, 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, compact disks (CDs), digital versatile disks (DVDs), caches, and / or any other storage devices or storage disks on which information is stored for any period of time (e.g., persistent, temporary, long-term, buffering, caching).

[0102] Using any of the above-described apparatuses (e.g., apparatus 100, 200, 300, or 400), a nucleic acid sequencing method can be performed that allows the reagent to retain at least substantially its chemical properties, and thus allows the apparatus to be used over a longer period of time. For example, using apparatus 100, 200, 300, or 400, a first portion of the reagent can be taken out of the well at a first time, and a second portion of the reagent can be taken out of the well at a second time, at least 36 hours after the first time, with little to no substantial decrease in the activity of the reagent chemistry due to oxidation of the reagent. In some embodiments, the second time may be at least 10 days after the first time, or in other embodiments, the second time may be at least 15 days after the first time.

[0103] 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.

[0104] When used herein, an element or step described in the singular and followed by the word "a" or "an" should be understood not to exclude multiple such elements or steps unless such exclusion is explicitly stated. Furthermore, a reference to "one embodiment" is not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the described features. Furthermore, unless explicitly stated otherwise, an embodiment that "comprises," "includes," or "having" one or more elements having a particular characteristic may include additional elements, whether or not they have that characteristic. In addition, terms such as "comprising," "including," and "having" are used interchangeably herein.

[0105] The terms “connect,” “connected,” “contact,” and “coupled” are defined broadly herein to encompass a variety of different arrangement and assembly techniques. These arrangements and techniques include, but are not limited to, (1) directly joining one component to another without any intervening components between them (i.e., the components are in direct physical contact), and (2) connecting one component to another with one or more components between them, provided that one component that is “connected,” “contacted,” or “coupled” to the other component is in some operational communication (e.g., electrical, fluid, physical, optical, etc.) with the other component (despite the presence of one or more additional components between them). It should be understood that some components that are in direct physical contact with each other may or may not be in electrical and / or fluid contact with each other. Furthermore, two electrically connected, electrically coupled, optically connected, optically coupled, fluidically connected, or fluidly coupled components may or may not be in direct physical contact, and one or more other components may be positioned between them.

[0106] The terms “approximately,” “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, small variations 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.

[0107] 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 embodiments may be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments. 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 given modules or units may be used, different or multiple types of given modules or units may be used, given modules or units may be added, or given modules or units may be omitted.

[0108] 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 to elements of the various embodiments 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.

[0109] 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 reagent cartridge equipped with wells, The reagents disposed in the well, An apparatus comprising: a floating lid disposed on the upper surface of the reagent in the well, the floating lid covering most of the upper surface of the reagent.

2. The apparatus according to claim 1, wherein the upper surface of the floating lid is convex.

3. The apparatus according to claim 1 or 2, wherein the floating cover is provided with a plurality of first projections located around the outer circumference of the floating cover and extending from the bottom surface of the floating cover.

4. The apparatus according to claim 3, wherein the floating cover is provided with a plurality of second projections located around the outer circumference of the floating cover and extending from the upper surface of the floating cover.

5. The apparatus according to claim 4, wherein the first plurality of protrusions are aligned in the axial direction with the second plurality of protrusions.

6. The apparatus according to any one of claims 1 to 5, wherein the float lid includes at least one opening formed through the float lid and configured to receive at least one of a sipper, a washing tube, and / or an additional reagent container.

7. The reagent cartridge comprises a plurality of side walls and end walls that form the well, and the apparatus is A support column having an external shape, configured to be positioned together with the well so as to be substantially parallel to the side wall, The floating cover includes a guide opening having substantially the same shape as the outer shape of the support column, The apparatus according to any one of claims 1 to 6, wherein the floating cover is disposed in the well with the support column extending through the guide opening.

8. The apparatus according to claim 7, comprising a support positioned at the end of the support column, wherein the support has at least two legs extending toward each of the side walls to each of the side walls.

9. The apparatus according to claim 8, wherein the support column and the support body form an integrated one-piece unit.

10. It is a device, A reagent cartridge equipped with wells, The reagents disposed in the well, An apparatus comprising: a plurality of plastic pellets disposed on the upper surface of the reagent in the well, the plurality of plastic pellets covering most of the upper surface of the reagent.

11. The apparatus according to claim 10, wherein each of the plurality of plastic pellets has at least one of the following shapes: a rectangular parallelepiped, an egg shape, a cylindrical shape, or a spheroid shape.

12. The apparatus according to claim 10 or 11, wherein each of the plurality of plastic pellets has a maximum axial length of about 3.0 to about 4.0 mm.

13. The apparatus according to claim 10 or 11, wherein each of the plurality of plastic pellets has a maximum axial length of less than approximately 1.5 mm.

14. It is a device, A reagent cartridge equipped with wells, The reagents disposed in the well, An apparatus comprising: an oil disposed on the upper surface of the reagent in the well, the oil covering the upper surface of the reagent.

15. The apparatus according to claim 14, wherein the oil is one of mineral oil or silicone oil.

16. It is a reagent cartridge, A body comprising an end wall and a plurality of side walls extending from the end wall, wherein the end wall and the plurality of side walls form a plurality of wells, and An opening extending through the end wall into one of the multiple wells, A floating lid is disposed in one of the multiple wells, A reagent cartridge comprising a cover disposed on the main body and covering at least a portion of the plurality of wells.

17. The reagent cartridge according to claim 16, comprising a reagent disposed in one of the plurality of wells, wherein the floating cap is disposed on the upper surface of the reagent and covers most of the upper surface of the reagent.

18. The reagent cartridge according to claim 16 or 17, wherein the upper surface of the float lid is convex.

19. The reagent cartridge according to any one of claims 16 to 18, wherein the float cover is positioned around the outer circumference of the float cover and comprises a plurality of first projections extending from the bottom surface of the float cover.

20. The reagent cartridge according to claim 19, wherein the float cover is provided with a plurality of second projections located around the outer circumference of the float cover and extending from the upper surface of the float cover.

21. The reagent cartridge according to claim 20, wherein the first plurality of protrusions are aligned in the axial direction with the second plurality of protrusions.

22. A support column having an external shape, configured to be positioned together with one of the plurality of wells so as to be substantially parallel to the side wall, The floating cover includes a guide opening having substantially the same shape as the outer shape of the support column, The reagent cartridge according to any one of claims 16 to 21, wherein the floating lid is disposed in the well with the support column extending through the guide opening.

23. The reagent cartridge according to claim 22, comprising a support positioned at the end of the support column, wherein the support has at least two legs extending toward each of the side walls.

24. The reagent cartridge according to claim 23, wherein the support column and the support body form an integrated one-piece unit.

25. It is a method, Fill at least a portion of the wells in the reagent cartridge with reagent, A method comprising: positioning the float lid on the upper surface of the reagent in the well such that the float lid covers most of the upper surface of the reagent.

26. The method according to claim 25, wherein the upper surface of the floating lid is convex.

27. The method according to claim 25, wherein the floating cover is provided with a plurality of first projections located around the outer circumference of the floating cover and extending from the bottom surface of the floating cover.

28. The method according to claim 27, wherein the float cover is provided with a plurality of second projections located around the outer circumference of the float cover and extending from the upper surface of the float cover.

29. The method according to claim 28, wherein the first plurality of protrusions are aligned in the axial direction with the second plurality of protrusions.

30. The method according to claim 25, wherein the float lid includes at least one opening formed through the float lid and configured to receive at least one of a sipper, a wash tube, and / or an additional reagent container.

31. The reagent cartridge comprises an end wall and a plurality of side walls extending from the end wall and defining the well, and the method is A support column having an outer shape is placed in the well substantially parallel to the side wall, The method of claim 25, comprising positioning the float lid in the well such that the support column extends through a guide opening in the float lid.

32. The method according to claim 31, wherein the support column comprises a support positioned at the end of the support column, and the support has at least two legs extending toward each of the respective side walls to the respective side walls.

33. The method according to claim 32, wherein the support column and the support body form an integrated one-piece unit.

34. It is a device, The main body comprises, A plurality of side walls and bottom surfaces forming a reagent reservoir, wherein the bottom surface is provided with a port, The reagent reservoir comprises a lid that is movably disposed within the reagent reservoir and has a projection extending toward the bottom surface, A device wherein the projection engages with the bottom surface to prevent the lid from obstructing the flow of fluid through the port.

35. The apparatus according to claim 34, further comprising a reagent disposed in the reagent reservoir.

36. The apparatus according to claim 34 or 35, wherein the reagent includes a liquid reagent.

37. The apparatus according to any one of claims 34 to 36, wherein the reagent reservoir has an opening, and further comprises a liquid-impermeable barrier covering the opening of the reagent reservoir.

38. A method for nucleic acid sequencing using the apparatus described in any one of claims 1 to 15 or 34 to 37, The first time period involves taking a first portion of the reagent from the well, A method comprising taking out a second portion of the reagent from the well at a second time which is at least 36 hours after the first time.

39. The method according to claim 38, wherein the second time is at least 10 days after the first time.

40. The method according to claim 38, wherein the second time is at least 15 days after the first time.

41. A method for nucleic acid sequencing using a reagent cartridge according to any one of claims 16 to 24, The first time period involves taking a first portion of the reagent from the well, A method comprising taking out a second portion of the reagent from the well at a second time which is at least 36 hours after the first time.

42. The method according to claim 41, wherein the second time is at least 10 days after the first time.

43. The method according to claim 41, wherein the second time is at least 15 days after the first time.

44. The apparatus according to any one of claims 1 to 15 or 34 to 43, wherein the reagent includes a dried reagent.

45. The reagent cartridge according to any one of claims 16 to 24, wherein the reagent includes a dried reagent.

46. The method according to any one of claims 25 to 33 or 38 to 43, wherein the reagent includes a dried reagent.

47. It is a device, A reagent cartridge equipped with wells, The reagents disposed in the well, An apparatus comprising a cover disposed over the well.

48. The apparatus according to claim 47, wherein the cover includes a floating lid disposed on the upper surface of the reagent in the well, and the floating lid covers most of the upper surface of the reagent.

49. The apparatus according to claim 47, wherein the cover contains oil disposed on the upper surface of the reagent in the well, and the oil covers the upper surface of the reagent.

50. The apparatus according to claim 47, wherein the cover includes a plurality of plastic pellets disposed on the upper surface of the reagent in the well, and the plurality of plastic pellets cover most of the upper surface of the reagent.

51. The apparatus according to claim 47, wherein the cover includes a plurality of pellets disposed on the upper surface of the reagent in the well, and the plurality of pellets cover most of the upper surface of the reagent.

52. The reagent cartridge according to claim 16, wherein the float cover is positioned around the outer circumference of the float cover and comprises a plurality of first projections extending from the bottom surface of the float cover.

53. The reagent cartridge according to claim 52, wherein the float cover is provided with a plurality of second projections located around the outer circumference of the float cover and extending from the upper surface of the float cover.

54. The reagent cartridge according to claim 53, wherein the first plurality of protrusions are aligned in the axial direction with the second plurality of protrusions.

55. A support column having an external shape, configured to be positioned together with one of the plurality of wells so as to be substantially parallel to the side wall, The floating cover includes a guide opening having substantially the same shape as the outer shape of the support column, The reagent cartridge according to claim 16, wherein the floating lid is disposed within the well with the support column extending through the guide opening.

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