Reagent containers and methods of use

Abstract

A reagent container includes a base defining a plurality of wells having openings exposed at an upper surface of the base and a tube receptacle. The plurality of wells includes a first set of wells and a second set of wells. Each well of the first set of wells has an opening to a well cylinder and a channel in communication with the well cylinder. The opening has a first portion disposed above the well cylinder and a second portion disposed above the channel. An area of the first portion is greater than an area of the second portion. An angle defined by a tangent of an inner surface of the first portion and the second portion at a junction between the first portion and the second portion is at least 100° and no greater than 180°.

Description

[0001] Cross Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 863,704, filed June 19, 2019, which is incorporated herein by reference in its entirety. TECHNICAL FIELD

[0003] The present disclosure relates generally to containers for storing and accessing reagents and various methods of using such containers. BACKGROUND

[0004] Laboratories increasingly seek instruments for performing tests on analytes. The preparation of such instruments can be labor intensive, relying on time-consuming reagent solution preparation. To reduce preparation time, the industry is moving toward pre-made reagent solutions provided to laboratory customers in kit form. However, the transport and handling of liquid reagents can lead to reagent degradation and spillage. Accordingly, improved reagent containers and instrument interfaces would be desirable. BRIEF DESCRIPTION OF DRAWINGS

[0005] The present disclosure can be better understood, and its numerous features and advantages can become apparent to those skilled in the art by reading the following specification in connection with the accompanying drawings.

[0006] Figure 1 Illustration including an example sequencing system.

[0007] Figure 2 Illustration including an example system in which a sensor array is included.

[0008] Figure 3 Illustration including an example sensor and associated microwell.

[0009] Figure 4 Illustration including an example analysis device.

[0010] Figure 5 Illustration including an example layout of an automated analysis device.

[0011] Figure 6 , Figure 7 and Figure 8 Illustration including an example reagent strip.

[0012] Figure 9 , Figure 10 and Figure 11 Illustration including an example base of a reagent strip.

[0013] Figure 12 Illustration including an example tube for use with a reagent strip.

[0014] Figure 13 ,Figure 14 and Figure 15 Illustration of an example top portion including a reagent strip.

[0015] Figure 16 Illustration of an end view including a well.

[0016] Figure 17 and Figure 18 Flowchart diagram including an example method for using a reagent strip.

[0017] The use of the same reference numbers in different drawings indicates the same or similar items. DETAILED DESCRIPTION

[0018] In an embodiment, a reagent strip can include a base defining a plurality of wells and a top disposed above and coupled to an upper surface of the base. The plurality of wells can include a first set of wells each having a well barrel and a channel in communication with the well barrel. The channel and well barrel are accessible through an opening. The opening can include a first portion that is larger than a second portion. The first portion is disposed above the well barrel and the second portion is disposed above the channel. In a specific example, the first portion and the second portion meet such that an inner surface of the opening perimeters of the first portion and the second portion form an angle of at least 90°, not greater than 180°, with a tangent line at the intersection of the first portion and the second portion. The plurality of wells can include a second set of wells that are larger or have a larger volume than the first set of wells. Optionally, the opening of each well in the second set of wells is larger than the opening of each well in the first set of wells. The base can further define a tube receptacle for coupling to a tube. In an example, the tube can be threadably connected to the tube receptacle of the base. Optionally, a thin film or foil, such as a metal or composite foil, can be applied over the openings of the plurality of wells prior to coupling the top portion over the base. The top portion can include a window through which the plurality of wells are accessible.

[0019] In a further embodiment, a method for providing reagent solutions includes applying a first reagent solution to a well in a first set of wells, applying a second reagent solution to a well in a second set of wells, and applying a thin film or foil over the openings of the plurality of wells. Each well in the first set of wells can include a different reagent solution, the same reagent solution, or a combination thereof. Similarly, each well in the second set of wells can include a similar reagent solution, a different reagent solution, or a combination thereof. The method can further include applying a reagent solution to a tube, sealing the tube, and attaching the tube to a tube receptacle of a base of a reagent container. A top portion can be applied over an upper surface of the base.

[0020] In another example, a method includes piercing a thin film or foil at a location disposed over a second portion of an opening of a well in a first set of wells, piercing the thin film or foil at a location over a first portion of the opening and over a well cylinder, and aspirating a reagent solution from the well cylinder of the well. The method can further include piercing the foil at a location disposed over a well in a second set of wells, and aspirating a solution from the well in the second set of wells. The method can also include piercing a foil disposed over a tube coupled with a tube holder, and aspirating a liquid from the tube.

[0021] Such reagent containers and methods for utilizing reagent containers are particularly useful in a variety of analytical devices. In particular, reagent containers can be used in analytical devices incorporating robotic liquid handling systems such as tri-axial robotic liquid handling systems. In an example, such reagent strips can be used in sample preparation devices such as Ion Torrent® ION AmpliSeq® TM Sequencer® Genexus TM Sequencer®

[0022] Figure 1 A system for performing pH-based nucleic acid sequencing is shown diagrammatically. Each electronic sensor of the device produces an output signal that depends on the value of a reference voltage. A fluidic circuit allows delivery of multiple reagents to a reaction chamber.

[0023] In Figure 1 , a system 100 containing a fluidic circuit 102 is connected by an inlet to at least two reagent reservoirs (104, 106, 108, 110, or 112), to a waste reservoir 120, and to a biosensor 134 by a fluidic pathway 132 that connects a fluidic node 130 with an inlet 138 of the biosensor 134 to achieve fluidic communication. Reagents from the reservoirs (104, 106, 108, 110, or 112) can be driven to the fluidic circuit 102 by a variety of methods, including pressure, pumps such as syringe pumps, gravity feed, etc., and selected by control of the valves 114. Reagents from the fluidic circuit 102 can be driven to the waste reservoir 120 by the valves 114 receiving signals from a control system 118. Reagents from the fluidic circuit 102 can also be driven to the waste reservoir 136 by the biosensor 134. The control system 118 contains a controller for the valves that produces signals for opening and closing by electrical connections 116.

[0024] The control system 118 also includes controllers for other components of the system, such as a wash solution valve 124 and a reference electrode 128 connected to the controller system by electrical connections 122. The control system 118 can also include control and data acquisition functions for the biosensor 134. In one mode of operation, the fluidic circuit 102, under programmed control of the control system 118, delivers a series of selected reagents 1, 2, 3, 4, or 5 to the biosensor 134, such that between the selected reagent flows, the fluidic circuit 102 is primed and washed, and the biosensor 134 is washed. Fluid entering the biosensor 134 exits through an outlet 140 and is deposited in a waste reservoir 136 by control of a pinch valve regulator 144. The valve 144 is in fluid communication with the sensor fluid output 140 of the biosensor 134.

[0025] The biosensor 134 can include a dielectric layer defining apertures that expose the sensor pads, and is particularly suitable for detecting chemical reactions and byproducts, such as detecting the release of hydrogen ions in response to nucleotide incorporation that can be used for genetic sequencing, among other applications. In particular embodiments, a sequencing system includes a flow cell in which a biosensor sensing array is disposed, includes communication circuitry in electronic communication with the sensing array, and includes a reservoir and fluidic controls in fluid communication with the flow cell. In one example, Figure 2 An expanded and cross-sectional view of the flow cell 200 is shown, and a portion of the flow chamber 206 is shown. The reagent 208 flows across the surface of the aperture array 202, with the reagent 208 flowing over the open ends of the apertures of the aperture array 202. The aperture array 202 and the sensor array 205 together can form an integrated unit that forms a lower wall (or floor) of the flow cell 200. The reference electrode 204 can be fluidically coupled to the flow chamber 206. Further, a flow cell cover 230 encloses the flow chamber 206 to contain the reagent flow 208 within a defined area.

[0026] Figure 3 An expanded and cross-sectional view of the flow cell 200 is shown, and a portion of the flow chamber 206 is shown. The reagent 208 flows across the surface of the aperture array 202, with the reagent 208 flowing over the open ends of the apertures of the aperture array 202. The aperture array 202 and the sensor array 205 together can form an integrated unit that forms a lower wall (or floor) of the flow cell 200. The reference electrode 204 can be fluidically coupled to the flow chamber 206. Further, a flow cell cover 230 encloses the flow chamber 206 to contain the reagent flow 208 within a defined area. Figure 2an expanded view of the well 301 and sensor 314 shown at 210. The volume, shape, aspect ratio (e.g., ratio of base width to well depth), and other dimensional characteristics of the well can be selected based on the nature of the reaction that occurs and the reagents, byproducts, or labeling techniques employed, if any. The sensor 314 can be a chemical field effect transistor (chemFET), more specifically an ion-sensitive FET (ISFET), having a floating gate 318 with a sensor plate 320 optionally separated from the interior of the well by a passivation layer 316. The sensor 314 can react to (and produce an output signal related to) the amount of charge 324 present on the passivation layer 316 opposite the sensor plate 320. Changes in the charge 324 can cause changes in the current between the source 321 and drain 322 in the chemFET. In turn, the chemFET can be used directly to provide a current-based output signal, or indirectly with additional circuitry to provide a voltage-based output signal. Reactants, wash solutions, and other reagents can be moved into and out of the well by diffusion mechanisms 340.

[0027] In an embodiment, the reaction that occurs in the well 301 can be an analytical reaction for identifying or determining a property or characteristic of an analyte of interest. Such a reaction can directly or indirectly produce a byproduct that affects the amount of charge proximate to the sensor plate 320. If such a byproduct is produced in small amounts or decays rapidly or reacts with other components, then multiple copies of the same analyte can be analyzed simultaneously in the well 301 to increase the output signal produced. In an embodiment, multiple copies of the analyte can be attached to a solid support 312 prior to or after deposition into the well 301. The solid support 312 can be a microparticle, nanoparticle, bead, solid, or porous including a gel or the like. For simplicity and ease of illustration, the solid support 312 is also referred to herein as a particle or bead. For nucleic acid analytes, multiple linked copies can be prepared by rolling circle amplification (RCA), exponential RCA, or similar techniques to produce amplicons without the need for a solid support.

[0028] Figure 4 An illustration of an example device 400 incorporating a tri-axial pipetting robot. In one instance, the device 400 can be a sequencer incorporating a sample pre- preparation platform. For example, the device 400 can include an upper portion 402 and a lower portion 404. The upper portion can include a door 406 for access to a deck 410 where sample, reagent containers, and other consumables are placed. The lower portion can include a cabinet for storage of additional reagent solutions and other components of the device 400. In addition, the system can include a user interface such as a touch screen display 408.

[0029] The deck 410 can include various locations where different reagent containers or sample containers are placed. For example, as shown in FIG. 4, the deck 410 can include a location 412 for a sample container, a location 414 for a reagent container, and a location 416 for a waste container. The locations 412, 414, and 416 can be arranged in any order and can include any number of locations. In addition, the locations can be arranged in any configuration, such as a linear array, a circular array, a grid, or any other configuration. The locations can be arranged in a configuration that is optimized for the particular sample preparation protocol being used. Figure 5As shown, the deck 500 of the apparatus can include a three-axis robotic pipetting system 502 and various locations for placing reagent solutions, samples, and other consumables for use by the apparatus. For example, consumables can include disposable pipette tips, single-use electronics, multi-well plates, and reagent strips, among other consumables. Consumable and reagent containers can be positioned, for example, at different locations such as receptacles 504, 506, 508, and 510. For example, a set of reagent strips can be seated at receptacle 504. Other reagent containers can be seated at receptacle 510. Plates containing samples, new pipette tips, or other consumables can be placed at other locations on the deck 500.

[0030] In an example, Figure 6 、 Figure 7 and Figure 8 A diagram including an example reagent container 600 is shown. The reagent container includes a base 602 and a top 604 coupled to the base 602. The top 604 includes a window 606 that enables access to a well 610 or 612. Optionally, the top 604 can provide a window 608 that enables access to a tube 614 inserted into a tube receptacle of the base 602.

[0031] The top can further include a grip 616. For example, the grip 616 can be used to hold the reagent container 600 when inserting the reagent container 600 into or removing the reagent container from an analysis apparatus. Further, the top 604 can define an end structure 618 or 620 that is configured to engage a complementary structure on an analysis device and limit the orientation of the reagent strip relative to a position within the analysis device.

[0032] As shown, Figure 7 The indexing receptacle 622 can be configured to receive an indexing pin or rod of an analysis apparatus on which the reagent container 600 is placed. This indexing pin or rod and complementary receptacle 622 can further limit the orientation of the area container within the analysis device and can limit movement of the reagent container. In particular, the end structures 618 and 620, along with the optional indexing receptacle 622, can ensure that the openings of the wells or tubes are positioned at locations programmed into a three-axis pipetting robot.

[0033] As shown, Figure 8 The base 602 can define a first set 824 of wells 610 and a second set 826 of wells 612. The base 602 can further define a tube receptacle for receiving a tube 614. The set of wells 824 can include 2 to 20 wells 610. For example, a set 824 of wells can include 4 to 16 wells, such as 6 to 12 wells 610. The set 826 of wells 612 can include one well, two wells, or more wells. For example, the set 826 can include one to six wells 612, such as two to four wells 612.

[0034] Figure 9 and Figure 10 An illustration of an example base 602 is included. The base 602 defines a well 610 that is accessible using an opening 930 at an upper surface of the base 602. The well 610 includes a well cylinder 932 and a channel 934 in fluid communication with the well cylinder 932. The well cylinder 932 extends the length of the well. The channel 934 is open along a portion of a side of the well cylinder 932. The opening 930 includes a first portion 936 disposed above the opening that accesses the well cylinder 932. The opening 930 can further include a second portion 938 that is open toward and disposed above the channel 934. In particular, the well cylinder 932 is configured to receive a pipette tip for aspirating a reagent solution from the well 610.

[0035] The opening 930 is defined by a perimeter 940 that extends around the first portion 936 and the second portion 938. As Figure 10 shown, at the intersection of the first portion 936 and the second portion 938, the perimeter 940 of the opening 930 defines an angle 1046 between a tangent 1048 to the perimeter of the first portion as the first portion approaches the intersection and a tangent 1050 to the perimeter of the second portion as the second portion approaches the intersection. In an example, the angle 1046 is greater than 90° and less than 180°. For example, the angle 1046 can be at least 100° and no greater than 180°. In particular, the angle can be at least 110° or at least 120°. In another example, the angle is no greater than 165° or no greater than 155°.

[0036] Figure 16 An illustration of an end view of the well 610 is included. The well includes an inner well cylinder 932 that extends the length 1684 of the well 610. The well cylinder 932 can terminate at a conical section 1686. The channel 934 can have a tapered configuration 1680 and have a side opening into the well cylinder 932 that extends a portion of the length 1684 of the well cylinder 932. For example, the side opening into the well cylinder can extend 5% to 50% of the length 1684 of the well cylinder 932, such as 10% to 35% of the length or 10% to 25% of the length.

[0037] Returning to Figure 9 , the base 602 further defines a well 612 having an opening 942. In an example, the volume of the well 612 defined by the base 602 can be greater than the well 610 defined by the base 602. In another example, the area of the opening 942 can be greater than the opening 930. Further, the shape of the opening 942 can be different than the opening 930.

[0038] The base 602 can further define a tube receptacle 944. The tube receptacle 944 can be configured to couple with a tube 614. In particular, the tube receptacle 944 can include a threaded coupling 946 to engage a complementary threaded coupling of the tube 614.

[0039] Optionally, prior to attaching the top 604 to the base 602, the openings of the wells, such as openings 930 or 942, can be sealed with a film or foil. For example, as shown in FIG. 11 IB, the openings 932 and 942 can be sealed with a film or foil 1152 to prevent leakage or exposure of the reagent solutions stored within the wells 610 or 612. In an example, the film or foil is not placed over the tube receptacle 944. The film or foil can be formed of a polymer, metal, or composite material. Figure 11

[0040] Figure 12 An example tube 1200 for coupling with the base 602 is shown. The tube 1200 includes a body 1202 having an opening 1206. A coupling mechanism, such as a threaded coupling 1204, can be formed on a side of the body 1202 of the tube 1200. Optionally, a film or foil 1208 can be applied over the opening 1206 of the tube 1200. The tube 1200 can be inserted into and coupled with the base 602 prior to or after coupling the top 604 to the base 602.

[0041] Figure 13 An illustration including the top 604 coupled with the base 602 from a bottom perspective view, Figure 14 An illustration including the top 604 without the base 602 from a bottom perspective view, and Figure 15 A perspective view of the top 604. The top 604 can include a clip 1362 or 1364 to couple with the base 602. Alternatively, the base 602 can include a clip to engage the top 604. Thus, the top 604 can be secured to the base 602.

[0042] The end structures 618 and 620 can be configured to engage complementary structures within an analytical device in which the container 600 is placed. In an example, the structures 618 and 620 can be equidistantly offset from a given side. For example, the structure 618 can be offset from a side 1368 by an amount 1354. The structure 620 can be offset from the side 1368 by an amount 1358. The offset amounts 1354 and 1358 can be equidistant. In another example, the structure 618 can be offset from a side 1370 by an amount 1356, and the structure 620 can be offset from the side 1370 by an amount 1360. In an example, the offset amounts 1356 and 1360 are equal. In another example, the offsets 1354 and 1358 can be different from the offsets 1356 and 1360.

[0043] ​The top 604 can further define an indexing receptacle 622 that receives a rod or pen to index the position of the reagent strip when inserted into complementary structures within an analysis device. These structures 618, 620, and 622 limit the possible orientations of the reagent strip or container 600 when inserted into an analysis device having complementary receptacles.

[0044] As shown, the top 604 can further include an information segment that indicates the properties of the reagent. For example, the top 604 includes a barcode or label 1570. Further, the top 604 can be colored in a manner that indicates its contents. For example, the top 604 can have a color (e.g., red, green, yellow, or blue) that can indicate what reagent is incorporated in the reagent container. Figure 15

[0045] An example method 1700 for preparing a reagent container is shown. As shown at block 1702, a base including a plurality of wells having openings at an upper surface of the base is provided. The plurality of wells can include a first set of wells each having a well barrel and an associated side channel. The plurality of wells can further include a second set of wells. The base can further define a tube receptacle. Figure 17 As shown at block 1704, a first reagent can be applied to one or more wells in the first set of wells. In one example, all of the wells in the first set can include a similar type of reagent solution. In another example, each of the wells in the first set can include a different reagent solution. In yet another example, some of the wells in the first set of wells can include the same reagent while other wells in the first set can include a different reagent.

[0046] As shown at block 1706, a second reagent solution is applied to wells in the second set of wells. The wells in the second set of wells can each include the same solution, a different solution, or a variation thereof.

[0047] As shown at block 1708, a film or foil can be applied over the upper surface of the base, thereby closing or sealing the openings of the wells. In one example, the film or foil does not extend over the tube receptacle. In particular, the film or foil can be used to individually seal the tubes prior to insertion into the base 602.

[0048] As shown at 1710, a top can be applied over the base. In one example, the top is clipped to the base. The top can include a window that allows access to the film or foil covered openings of the base. Further, the top can have a color that indicates the set of reagents stored within the base.

[0049] Optionally, as shown at block 1712, a tube can be inserted into the tube receptacle. Alternatively, the tube can be inserted into the base prior to application of the top.

[0050] ​

[0051] The reagent container is supported in an analytical device for the specific purpose of supplying reagents. Figure 18 An example method 1800 for using a reagent container is illustrated. For example, a reagent container can be provided and inserted into an analytical device, as shown at block 1802. The analytical device can include a three-axis pipetting robot, for example. In an example, the analytical device includes a complementary receptacle for receiving the reagent container. Specifically, the complementary receptacle can include a shape and structure or indexing pins or rods that are adapted to the associated structure on the reagent container.

[0052] In an example, the pipetting robot can obtain a pipette tip, as shown at block 1804. The pipetting robot can use the pipette tip to pierce a foil or film disposed over an opening to one of the wells of the reagent container. In an example, the three-axis pipetting robot pierces the film or foil at a location disposed over a channel of the well above a portion of the opening to the well, as shown at block 1806.

[0053] The three-axis pipetting robot can pierce the foil or film at a second location disposed over the well barrel and another portion of the opening, as shown at 1808. Specifically, the three-axis robot can drive the tip into the well barrel a sufficient depth to draw a desired amount of reagent from the well barrel, and can draw the reagent from the well, as shown at block 1810. The first piercing over the channel can allow air to enter the well when the pipette is withdrawn from the well while drawing the reagent solution from the well. Thus, a vacuum is avoided.

[0054] The three-axis pipetting robot can dispense the reagent solution and perform other functions before drawing another reagent solution from the reagent container. For example, if a reagent is desired that is disposed in a well of a second set of wells, the pipetting robot can obtain a new tip, as shown at block 1812, and the pipetting robot can use the new tip to pierce a film or foil disposed over an opening to the well of the second set of wells, as shown at block 1814. The reagent can be drawn from the well, as shown at block 1816, and the system can perform other functions before it is desired to obtain additional reagents from the reagent container.

[0055] When a reagent solution is desired that is disposed in a removable tube, the three-axis pipetting robot can obtain a new tip, as shown at block 1818. The three-axis robot can pierce a film or foil disposed over an opening to the tube, as shown at block 1820, and can draw the reagent solution from the tube, as shown at block 1822.

[0056] When the operation is complete, the reagent container can be removed from the analytical device, as shown at block 1824. Optionally, the tube can be separated from the reagent container, as shown at block 1826. The reagent tube and the reagent container can be disposed separately as desired.

[0057] In a first aspect, a reagent container includes a base defining a plurality of wells and a tube receptacle, the plurality of wells having openings exposed at an upper surface of the base. The plurality of wells includes a first set of wells and a second set of wells. Each well of the first set of wells has an opening to a well barrel and a channel in communication with the well barrel. The opening has a first portion disposed above the well barrel and a second portion disposed above the channel. An area of the first portion is greater than an area of the second portion. An angle defined by a tangent of an inner surface of the first portion and the second portion at a junction between the first portion and the second portion is at least 100° and no greater than 180°. The reagent container further includes a top coupled above a top surface of the base and defining a window that enables access to the openings of the plurality of wells and the tube receptacle.

[0058] In an example of the first aspect, a volume of a well of the second set of wells is greater than a volume of a well of the second set of wells.

[0059] In another example of the first aspect and above examples, an opening of each well of the second set of wells is greater than an opening of each well of the first set of wells.

[0060] In a further example of the first aspect and above examples, each well of the second set of wells is free of a side channel.

[0061] In an additional example of the first aspect and above examples, the reagent container further includes a tube, the tube receptacle being removably coupled to the tube. For example, the tube receptacle has a threaded coupling to threadably couple with the tube.

[0062] In another example of the first aspect and above examples, the reagent container further includes a film disposed above a top surface of the base and covering openings of the plurality of openings.

[0063] In a further example of the first aspect and above examples, the angle is no greater than 165°. For example, the angle is no greater than 150°.

[0064] In a further example of the first aspect and above examples, the angle is at least 120°. For example, the angle is at least 130°.

[0065] In another example of the first aspect and above examples, the top includes a clip to couple with the base.

[0066] In a further example of the first aspect and above examples, the top includes a handle extending vertically away from the top surface of the base.

[0067] In a further example of the first aspect and the above examples, the top further defines an indexing receptacle.

[0068] In another example of the first aspect and the above examples, the top has a first end and a second end, the first end and the second end being horizontally offset equidistant from an edge of the top.

[0069] In a second aspect, a method for providing reagents to an analytical device includes, in a reagent container including a base and a top, the base defining a plurality of wells and a tube receptacle, the plurality of wells having openings exposed at an upper surface of the base, the plurality of wells including a first set of wells and a second set of wells, each well in the first set of wells having an opening to a well cylinder and a channel in communication with the well cylinder, the opening having a first portion disposed above the well cylinder and a second portion disposed above the channel, an area of the first portion being greater than an area of the second portion, an angle defined by a tangent of an inner surface of the first portion and the second portion at a connection point between the first portion and the second portion being at least 100° and no greater than 180°, the top coupled above a top surface of the base and defining a window that enables access to the openings of the plurality of wells and the tube receptacle: piercing a foil with a pipette tip attached to an automated pipetting robot at a position disposed above the second portion of the opening and above the channel of a well in the first set of wells; piercing the foil with the pipette tip attached to the automated pipetting robot at a position disposed above the first portion of the opening and above the well cylinder of the well in the first set of wells; and aspirating a reagent from the well cylinder of the well in the first set of wells using the pipette tip.

[0070] In an example of the second aspect, the method further includes piercing the foil with a second pipette tip attached to the automated pipetting robot at a position disposed above a well in the second set of wells; and aspirating a second reagent from the well in the second set of wells. For example, the method further includes piercing a foil disposed above an opening of a tube with a third pipette tip attached to the automated pipetting robot, the tube disposed in the tube receptacle; and aspirating a third reagent from the tube.

[0071] In a third aspect, a method for providing reagents to an analytical device includes: in a reagent container including a base and a top, the base defining a plurality of wells and a tube receptacle, the plurality of wells having openings exposed at an upper surface of the base, the plurality of wells including a first set of wells and a second set of wells, each well in the first set of wells having an opening to a well cylinder and a channel in communication with the well cylinder, the opening having a first portion disposed above the well cylinder and a second portion disposed above the channel, an area of the first portion being greater than an area of the second portion, an angle defined by a tangent of an inner surface of the first portion and the second portion at a connection point between the first portion and the second portion being at least 100° and no greater than 180°, the top coupled above a top surface of the base and defining a window that enables access to the openings of the plurality of wells and the tube receptacle: applying a first reagent to a well in the first set of wells through the first portion of the opening; applying a second reagent to a well in the second set of wells; and attaching a foil over the openings of the plurality of wells.

[0072] In an example of the third aspect, the method further includes coupling a tube to the tube receptacle, the tube including a third reagent and a separate foil cap.

[0073] It should be noted that not all of the activities described above in the general description or the examples are required, that a portion of a specific activity can not be required, and that one or more further activities can be performed in addition to those described. Still further, the order in which activities are listed are not necessarily the order in which they are performed.

[0074] In the foregoing specification, concepts have been described with reference to specific embodiments. However, one of ordinary skill in the art appreciates that various modifications and changes can be made without departing from the scope of the present application as set forth in the claims below. Accordingly, the specification and figures are to be regarded in an illustrative rather than a restrictive sense, and all such modifications are intended to be included within the scope of the present application.

[0075] As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article, or apparatus that comprises a list of features is not necessarily limited only to those features but can include other features not expressly listed or inherent to such process, method, article, or apparatus. In addition, "or" as used herein is intended to cover an inclusive or, such that any one of the listed features can be present alone, or in combination with one or more of the other features. For example, the following are all satisfied: A or B, where A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and A and B are both true (or exist).

[0076] Also, "a" or "an" is used to describe elements and components described herein. This is done merely for convenience and to give a general sense of the scope of the application. This description should be read to include one or at least one and the singular also includes the plural unless it is explicitly stated otherwise.

[0077] Benefits, other advantages, and solutions to problems have been described above with regard to specific embodiments. However, the benefits, advantages, solutions to problems and any one or more of the features, can be implemented or contributed by other features not expressly described above.

[0078] Upon reading this description, those skilled in the art will appreciate that certain features are described in the context of separate embodiments and separate embodiments can also be provided in combination with one another. Conversely, various features described in the context of a single embodiment can also be provided separately or in any suitable sub-combination. Moreover, reference to a range of values includes each value within the range.

Claims

1. A reagent container comprising: a base defining a plurality of wells and a tube receptacle, the plurality of wells having openings exposed at an upper surface of the base, the plurality of wells including a first set of wells and a second set of wells, each well of the first set of wells having an opening at the upper surface of the base, wherein the opening leads to a well barrel and a channel in communication with the well barrel, the opening having a first portion disposed above the well barrel and a second portion disposed above the channel, the first portion having an area greater than an area of the second portion, the channel having a tapered configuration and having a side opening to the well barrel extending from the upper surface of the base along a portion of the well barrel length, an angle defined by a tangent to inner surfaces of the first portion and the second portion when the inner surfaces approach a connection point between the first portion and the second portion being at least 100° and no greater than 155°; and a top coupled above a top surface of the base and defining a window that provides access to the openings of the plurality of wells and the tube receptacle; wherein a volume of a well of the second set of wells is greater than a volume of a well of the first set of wells, wherein the opening of each well of the second set of wells is greater than the opening of each well of the first set of wells.

2. The reagent container of claim 1, wherein each well of the second set of wells is free of a side channel.

3. The reagent container of claim 1, further comprising a tube, the tube receptacle being removably coupled to the tube.

4. The reagent container of claim 3, wherein the tube receptacle has a threaded coupling to threadably couple with the tube.

5. The reagent container of claim 1, further comprising a film disposed above the top surface of the base and covering openings of the plurality of openings.

6. The reagent container of claim 1, wherein the angle is at least 120°.

7. The reagent container of claim 6, wherein the angle is at least 130°.

8. The reagent container of claim 1, wherein the top includes a clip to couple with the base.

9. The reagent container of claim 1, wherein the top includes a handle extending vertically away from the top surface of the base.

10. The reagent container of claim 1, wherein the top further defines an indexing receptacle to receive an indexing pin or rod.

11. The reagent container of claim 1, wherein the top has first and second end structures configured to engage complementary structures within an analysis device, the first and second end structures being disposed at respective first and second ends and equidistantly offset from one of the vertical sides of the top.

12. A method for providing reagents to an analysis device, the method comprising: on a reagent container including a base and a top, the base defining a plurality of wells and a tube receptacle, the plurality of wells having openings exposed at an upper surface of the base, the plurality of wells including a first set of wells and a second set of wells, each well of the first set of wells has an opening at an upper surface of the base, wherein the opening leads to a well barrel and a channel in communication with the well barrel, the opening having a first portion disposed above the well barrel and a second portion disposed above the channel, the channel having a tapered configuration and having a side opening leading to the well barrel that extends from the upper surface of the base along a portion of the well barrel length, the first portion has a first perimeter and the second portion has a second perimeter, the second perimeter intersecting the first perimeter at a junction, an angle defined by a tangent to the first perimeter of the first portion and the second perimeter of the second portion at a point of connection between the first and second perimeters proximate the first portion and the second portion is at least 100° and no greater than 155°, the top is coupled above the top surface of the base and defines a window that provides access to the openings of the plurality of wells and the tube receptacle; wherein a volume of a well of the second set of wells is greater than a volume of a well of the first set of wells; and wherein an opening of each well of the second set of wells is larger than an opening of each well of the first set of wells; piercing a foil at a location disposed above the second portion of the opening and above the channel of a well of the first set of wells with a pipette tip attached to an automated pipetting robot; piercing the foil at a location disposed above the first portion of the opening and above the well barrel of the well of the first set of wells with the pipette tip attached to the automated pipetting robot; and aspirating a reagent from the well barrel of the well of the first set of wells using the pipette tip.

13. The method of claim 12, further comprising: piercing a foil at a location disposed above a well of the second set of wells with a second pipette tip attached to the automated pipetting robot; and aspirating a second reagent from the well of the second set of wells.

14. The method of claim 13, further comprising: piercing a foil at a location disposed above an opening of a tube in the tube receptacle with a third pipette tip attached to the automated pipetting robot; and aspirating a third reagent from the tube.

15. A method for providing reagents to an analytical device, the method comprising: In a reagent container comprising a base and a top, the base defines a plurality of wells and a tube receptacle, the plurality of wells having openings exposed at an upper surface of the base, the plurality of wells comprising a first set of wells and a second set of wells, each well in the first set of wells having an opening at the upper surface of the base, wherein the opening leads to a well cylinder and a channel in communication with the well cylinder, the opening having a first portion disposed above the well cylinder and a second portion disposed above the channel, the channel having a tapered configuration and having a side opening to the well cylinder extending along a portion of the well cylinder length from the upper surface of the base, the first portion having a larger area than the second portion, an angle defined by a tangent to inner surfaces of the first portion and the second portion when the inner surfaces approach a connection point between the first portion and the second portion being at least 100° and no greater than 155°, wherein a volume of a well in the second set of wells is greater than a volume of a well in the first set of wells; and wherein an opening of each well in the second set of wells is larger than an opening of each well in the first set of wells; the top coupled above a top surface of the base and defining a window that enables access to the openings of the plurality of wells and the tube receptacle; applying a first reagent to a well in the first set of wells through the first portion of the opening; applying a second reagent to a well in the second set of wells; and attaching a foil over the openings of the plurality of wells.

16. The method of claim 15, further comprising coupling a tube to the tube receptacle, the tube comprising a third reagent and a separate foil cover.

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