Reduced area array of pre-aliquoted reagent cartridges for a library preparation system

Abstract

An array of reagent cartridges for a library preparation system includes a plurality of reagent cartridges, each reagent cartridge in the plurality of reagent cartridges having a central axis and a cross-sectional major axis and a cross-sectional minor axis, and each reagent cartridge in the plurality of reagent cartridges being configured to be accessible by a pipette of a library preparation system. Each reagent cartridge is spaced from an adjacent reagent cartridge in the array in an X direction and in a Y direction, the spacings in the X direction and the Y direction being unequal.

Description

REDUCED AREA ARRAY OF PRE-ALIQUOTED REAGENT CARTRIDGES FOR A LIBRARY PREPARATION SYSTEMCross-Reference To Related Applications

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 613,571 , filed December 21 , 2023, and entitled “Reduced Area Array of Pre-Aliquoted Reagent Cartridges for a Library Preparation System”, which is incorporated herein by reference in its entirety.FIELD OF DISCLOSURE

[0001] The present application generally relates to library preparation systems, and more specifically to library preparation systems including an array of pre-aliquoted reagent cartridges having an area reduced footprint.BACKGROUND

[0002] Library preparation systems generally include working areas where an assay is stored, consumable areas for storing additives, such as reagents and other consumables used for library preparation, and loading areas, for loading and / or transferring a prepared sample to a system such as a sequencing system. Each of these areas generally includes an array of containers or cartridges that hold the various components (e.g., samples, reagents, disposable tips, etc.). Increasing the capacity of a library preparation system includes adding more containers or cartridges to the array, which increases the area or footprint of the array in the system, and thus the area of the system itself.SUMMARY

[0003] Shortcomings of the prior art can be overcome, and benefits as described in this disclosure can be achieved, through systems and devices for increasing the density of container or cartridge arrays, which reduces the area footprint of such cartridge arrays, in a library preparation system. Various implementations of the systems and devices are described below, and the systems and devices in any combination, may overcome these shortcomings and achieve the benefits described herein.

[0004] As discussed above, a library preparation system may generally include consumables areas, working areas, and loading areas. In at least some embodiments, the working area may be referred to as an assay bay or a plurality of assay bays (e.g., first and second assay bays). The consumable areas may be used to load and store reagents and consumables needed for the library preparation process, the consumables may include, but are not limited to, disposable tips, wet or dry assay specific reagents, wet or dry bulk reagents, and reaction plates and wells. The consumables area may include a consumablesreceptacle which may include a tray configured to hold an array of reagent cartridges or containers.

[0005] In a first implementation, an array of reagent cartridges for a library preparation system includes a plurality of reagent cartridges, each reagent cartridge in the plurality of reagent cartridges having a central volume axis, a cross-sectional major axis and a cross-sectional minor axis, and each reagent cartridge in the plurality of reagent cartridges being configured to be accessible by a pipette of a library preparation system. Each reagent cartridge in the plurality of reagent cartridges is spaced from an adjacent reagent cartridge in the array in an X (or first) direction and in a Y (or second) direction, and the spacings in the X direction between adjacent reagent cartridges are equal and the spacings in the Y direction between adjacent reagent cartridges are equal, but spacing between adjacent reagent cartridges in the X direction are unequal to spacings between adjacent cartridges in the Y direction.

[0006] In a second implementation, a library preparation system includes an assay bay, the assay bay being configured to prepare a library of samples, a consumable area including a reagent cartridge receptacle, and an array of reagent cartridges disposed in the reagent cartridge receptacle. The array or reagent cartridges includes a plurality of reagent cartridges, each reagent cartridge in the plurality of reagent cartridges having a central volume axis and a cross-sectional major axis and a cross-sectional minor axis. Each reagent cartridge is spaced from an adjacent reagent cartridge in the array in an X (or first) direction and in a Y (or second) direction, and the spacings in the X direction between adjacent reagent cartridges are equal and the spacings in the Y direction between adjacent reagent cartridges are equal, but spacing between adjacent reagent cartridges in the X direction are unequal to spacings between adjacent cartridges in the Y direction.

[0007] In further accordance with the foregoing the first or second implementations, the system may further include or comprise any one or more of the following features.

[0008] In an implementation, the major axis of at least one reagent cartridge of the plurality of reagent cartridges is larger than the minor axis.

[0009] In another implementation, an aspect ratio of at least one reagent cartridge of the plurality of reagent cartridges is less than 3:1 .

[0010] In yet another implementation, the aspect ratio of at least one reagent cartridge of the plurality of reagent cartridges is less than 2:1 .

[0011] In yet another implementation, at least one reagent cartridge of the plurality of reagent cartridges has an oval-shaped cross-section.

[0012] In yet another implementation, at least one reagent cartridge of the plurality of reagent cartridges has an ellipse-shaped cross-section.

[0013] In yet another implementation, at least one reagent cartridge of the plurality of reagent cartridges has a rectangular-shaped cross-section.

[0014] In yet another implementation, a first reagent cartridge of the plurality of reagent cartridges has a different shape from a second reagent cartridge of the plurality of reagent cartridges.

[0015] In yet another implementation, a first reagent cartridge of the plurality of reagent cartridges has a different size from a second reagent cartridge of the plurality of reagent cartridges.

[0016] In yet another implementation, a first reagent cartridge of the plurality of reagent cartridges has a circular cross-sectional shape with a first diameter and a second reagent cartridge of the plurality of reagent cartridges has a second diameter, the first diameter being larger than the second diameter.

[0017] In yet another implementation, spacing between adjacent reagent cartridges of the plurality of reagent cartridges in the X direction is larger than spacing between adjacent reagent cartridges in the Y direction.

[0018] In yet another implementation, a pipette is included and each reagent cartridge in the plurality of reagent cartridges is configured to be accessible by the pipette.

[0019] In yet another implementation, the pipette is mounted on a cross bay gantry and the pipette is movable in an X direction and in a Y direction.

[0020] In yet another implementation, the pipette has a plurality of pipette tips.

[0021] In yet another implementation, the assay bay comprises a plurality of sample wells.BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG. 1 is a top view of a library preparation system.

[0023] FIG. 2 is a front view of the system of FIG. 1 .

[0024] FIG. 3 is an isometric view of the system of FIG. 1 .

[0025] FIG. 4A is a first example of a prior art reagent reservoir arrangement in combination with sample wells;

[0026] FIG. 4B is a second example of a prior art reagent reservoir arrangement in combination with sample wells;

[0027] FIG. 4C is a generic representation of the prior art reagent reservoir arrangement of FIG. 4B, but without the sample reservoirs for ease of comparison;

[0028] FIG. 5A is a first example of an array of reagent reservoirs constructed in accordance with the disclosure;

[0029] FIG. 5B is a second example of an array of reagent reservoirs constructed in accordance with the disclosure; and

[0030] FIG. 5C is a third example of an array of reagent reservoirs constructed in accordance with the disclosure.

[0031] FIG. 6 illustrates a schematic diagram of the library preparation system of claim 1 , including a control system.DETAILED DESCRIPTION

[0032] Although the following text discloses a detailed description of implementations of methods, apparatuses and / or articles of manufacture, it should be understood that the legal scope of the property right is defined by the words of the claims set forth at the end of this patent. Accordingly, the following detailed description is to be construed as examples only and does not describe every possible implementation, as describing every possible implementation would be impractical, if not impossible. Numerous alternative implementations could be implemented, using either current technology or technology developed after the filing date of this patent. It is envisioned that such alternative implementations would still fall within the scope of the claims.

[0033] At least one aspect of this disclosure is related to arrays of reagent cartridges or containers that increase cartridge or container density without increasing the overall area occupied by the array of reagent cartridges or containers. Anther aspect of the disclosure is related to arrays of reagent cartridges or containers that have a reduced area footprint, relative to existing arrays of reagent cartridges or containers having the same number of individual cartridges or containers.

[0034] The disclosed implementations increase throughput or capacity of a library preparation system by allowing more reagent cartridges or containers to be contained in an existing area footprint limitation. The disclosed implementations of arrays of reagent cartridges or containers allow a library preparation system to process larger numbers of samples requiring larger numbers of individual or unique reagents for processing, without increasing the area footprint of the existing library preparation system.

[0035] The size of traditional liquid handling instruments of the library system is typically driven by the number of reagents, the number of reaction reservoirs, and thenumber of pipette tips required by the assay. These consumables are typically laid out in a horizontal plane, placed side-by-side, and are accessible to a pipette riding on an XYZ gantry, as illustrated in FIG. 1 , for example. This arrangement forces the overall dimensions of the instruments to increase when supporting more complicated workflows with more reagents, wells, and tips, which requires a larger area size footprint for the library preparation system. However, the area footprint of the library preparation system is practically limited by the size of a lab bench or other working surface on which the library system is disposed.

[0036] As illustrated in FIGS. 1-3, a library preparation system 200 may include one or more consumables areas 302, a first working area 304 optionally having two working bays 304A, 304B, an optional second working area 306, and a loading area. In at least some embodiments, the first working area 304 may be referred to as an assay bay and the second working area 306 may be referred to as a common resource bay. In other implementations, the library preparation system may include a single working area 304.

[0037] The consumable areas 302 may include one or more consumable receptacles that may be used to load and store reagents and consumables needed for a library preparation process, including, disposable tips, wet or dry assay specific reagents, wet or dry bulk reagents, and reaction plates and wells. The consumables, such as reagent, are typically stored in an array, for example an array 111 of individual reagent cartridges 154.

[0038] Referring now to FIG. 4A, previous attempts to reduce footprint size of reagent cartridges have included loading reagents into bulk reservoirs 54 and then distributing each reagent to each sample well 24 at the time-of-use serially (only eight sample wells are illustrated for clarity, but typical library systems may have twenty four or more sample wells). In other words, the first regent is delivered from the first reagent reservoir 54 to each sample well 24, then the second reagent is delivered from the second reagent reservoir 54 to each sample well 24, and so on, in a serial nature, depositing each reagent in each sample well 24 one at a time. All sample wells 24 are loaded with the first reagent before the second reagent is loaded. This approach allows the reagents to be stored in bulk in fewer containers. However, this serial nature of the reagent delivery significantly increases run time by requiring as many pipetting steps as there are sample wells 24 (eight sample wells in the illustrated example) multiplied by the number of reagents in the assay (four reagents are illustrated in the example), which in the illustrated embodiment would be thirty two total pipetting steps.

[0039] Turning now to FIG. 4B, another known reagent organizational approach is illustrated that reduces run time by reducing the number of movements required by a pipette(not shown in FIG. 4B). By pre-aliquoting reagents into individual reagent reservoirs, containers, or cartridges 54, one-per-sample, and arranging the pre-aliquoted reagent cartridges 54 in an array 11 , run time may be significantly reduced by using a multi-channel pipette to pipette reagents to all sample wells 24 (eight sample wells are illustrated, but as stated earlier, twenty four or more sample wells are commonly used), in parallel, thus reducing the number of movements required by the pipette to deliver reagents to the sample wells 24. For example, in the example illustrated in FIG. 4B, only four pipette movements are needed to deliver the reagents to the sample sells 24, one pipette movement for each reagent, because the pipette has multiple tips, one for each sample well 24. The drawback of this approach is that the individual reagent cartridges 54 in the array 11 significantly increase the area footprint of the array (represented by dashed box A), when compared to bulk reservoirs, or when adding reagents. While such pre-aliquoted reagents reduce run time, increasing the number of pre-aliquoted reagents necessarily increases the footprint or area of the array 11 of reagent cartridges 54 as the number of reagent cartridges 53 increases, which increases the overall size of the library system.

[0040] Referring now to FIG. 4C another known array 11 of reagent cartridges 54 is illustrated. The array 11 of reagent cartridges 54 of FIG. 4C is identical to the array 11 of reagent cartridges 54 of FIG. 4B, with the sample wells 24 omitted for ease of comparison. Known arrays 11 of reagent cartridges 54 have uniform circular cross-sectional dimensions (e.g., approximately 7 mm in diameter) and are evenly spaced between central volume axes B of the reagent cartridges 54 (which extend in the Z direction, for example the central axis of a cylindrical or cone-shaped reagent cartridge). In other words, spacing Sxbetween central axes B of adjacent reagent cartridges 54 in the X direction is equal to spacing Syof adjacent reagent cartridges 54 in the Y direction. In the example illustrated in FIG. 4C, the central axes B of the reagent cartridges 54 are spaced approximately 9 mm from one another and the entire array 11 of reagent cartridges 54 measures approximately 37 mm in a Y direction and approximately 79 mm in the X direction. This standard spacing allows standardized manufacturing equipment with 9 mm pitch pipettes to fill the consumables.

[0041] Turning now to FIGS. 5A-C, embodiments of an array 111 of reagent cartridges 154 is illustrated that reduces the overall footprint or area of the array 111 , without decreasing the number of reagent cartridges 154, and without changing the standardized pitch in the X direction. This standardized pitch in the X direction allows a standard pipette to be used to fill the sample wells, so that the disclosed arrays 111 may be implemented in existing library preparation systems that use standard pipettes. Some of the disclosed arrays 111 reduce the footprint in the Y direction by 30 % or more as compared to standarduniformly spaced arrays of reagent cartridges, such as the arrays illustrated in FIGS. 4B and 40.

[0042] Generally, the Y direction of the array 111 is reduced in three ways in the illustrated examples, 1) by changing the shape of the well to a shape having a smaller Y dimension then an X dimension, such as an ellipse or an oval, rather than a circle, to maintain a smooth perimeter with no corners as illustrated in FIG. 5B; 2) by changing the well to an angled or non-circular shape having a smaller Y dimension than an X dimension, such as a rectangular shape or a polygon, to make better use of the available surface area, as illustrated in FIG. 5B; and 3) by reducing the size of certain circular wells when only a small volume is needed, and maintaining standard sized wells when more volume is needed, as illustrated in FIG. 5C. In the embodiments of FIGS. 5A and 5B, the reagent cartridge 154 shapes have a major axis Mi and a minor axis M2. The major axis Mi is larger than the minor axis M2. Both the major axis Mi and the minor axis M2are symmetrical axes for the cross-sectional shape of the reagent cartridge 154.

[0043] In other embodiments, the shapes may be mixed. For example, some rows in the array 111 may include oval or ellipse shaped reagent cartridges 154 while other rows in the array 111 may include rectangular or polygonal shaped reagent cartridges.

[0044] Because a reagent cartridge has dedicated, purposely designed well for each reagent, the geometry can be adjusted for each volume. In an example array 111 with thirty two reagent cartridges 154 where twenty four of the reagent cartridges 154 are less than 120 uL in volume, as illustrated in FIG. 5C, then smaller diameter reagent reservoir, such as a 4.5 mm diameter reagent reservoir 154, can be implemented in some rows in the array 111 to reduce the Y dimension of the array 111.

[0045] While the Y dimension of the arrays 111 are reduced, the standard pitch or spacing in the X direction is maintained. This allows standardized manufacturing equipment, for example equipment with 9 mm pitch pipettes to fill the consumables, such as reagent cartridges, to be used, thereby saving manufacturing capital equipment costs.

[0046] One challenge with reducing the separation between consumable cartridges is the increased risk of cross contamination. For consumables that contain samples that need to be kept separate, this tighter packing can increase the risk of contamination. However, for reagent cartridges, this risk is low because the fluid being manipulated is a reagent usually common to all samples, with a few exceptions. In addition, consumables pre-filled with reagents generally have a foil seal that, when pierced, helps reduce the risk of cross contamination by covering the majority of the open surface area when pipetting. One benefit of the disclosed arrays of reagent cartridges is, however, that the proposed arrays ofreagent cartridges maintain a standard and uniform X direction separation (e.g., in some implementations about a 9 mm separation) between individual reagent cartridges in the array in the X direction so the risk of cross contamination is not increased as it would in a consumable with a smaller pitch, such as a 4.5 mm pitch in the X direction.

[0047] In other embodiments of a library preparation system, where an X motion axis is added for the pipette, the arrays of reagent cartridges could be further modified to reduce spacing in the X direction. For example, if an X motion axis is added, then smaller reagent cartridges, for example the smaller reagent cartridges 154 illustrated in FIG. 5C could be packed more closely (e.g., hexagonal close pack) to further reduce the Y dimension of the array.

[0048] Experimental testing has shown that the aspect ratio of the reagent cartridge affects mixing performance. When an aspect ratio between the X and Y dimensions (cross- sectional or top view), more specifically a ratio between the major axis Mi and the minor axis M2of the reagent cartridge 154, is less than about 3:1 and preferably less than about 2:1 , mixing problems are reduced. The longer and narrower nature of reagent cartridges having an aspect ratio larger than about 3:1 inhibits mixing, particularly when the pipette cannot move in the X direction and cannot reach the ends of the longer and narrower reagent cartridge.

[0049] Turning now to FIG. 6, a schematic diagram of an implementation of a library preparation system 100 that may include the above described arrays 111 of reagent cartridges 154 is illustrated. The exemplary library preparation system may optionally include a system for managing the library preparation system. However, the described optional system for managing the library preparation system is not required to implement the disclosed arrays 111 of reagent cartridges 154 and the arrays 111 of reagent cartridges 154 may be implemented in other library preparation systems. In the disclosed example, the system 100 may be used to automatically, easily, and efficiently prepare DNA libraries for sequencing applications, for example. The system 100 may prepare the libraries when performing workflows such as whole genome sequencing workflows, DNA & RNA enrichment workflows, methylation workflows, split-pool amplicon workflows, amplicon workflows. The workflows may include one or more steps, such as amplification processes, cleanup processes, quantification processes, library normalization processes, pooling processes, denaturing processes, and / or diluting processes in some implementations.

[0050] The system may include a controller 176. The controller may be electrically and / or communicatively coupled to one or more components of the system 100 to perform various functions as described herein. The controller 176 may include a user interface 221 ,a communication interface 222, one or more processors 224, and a memory 226 storing instructions executable by the one or more processors 224 to perform the various functionalities described herein.

[0051] The user interface 221 may receive input from a user, and provide information to the user associated with the operation of the system 100 (e.g., information about the workflows being scheduled and / or taking place). The user interface 221 may include a touch screen, a display, a key board, a speaker(s), a mouse, a track ball, and / or a voice recognition system. The touch screen and / or the display may display a graphical user interface (GUI).

[0052] The system 100 may include the communication interface 222 to enable communication between the system 100 and one or more components, such as a remote system(s) (e.g., computers) using one or more network(s). The network(s) may include an intranet, a local-area network (LAN), a wide-area network (WAN), the intranet, etc. Some of the communications may be associated with workflows of the system 100, such as scheduling one or more workflows.

[0053] The system 100 may include one or more processors 224 and / or processorbased system(s) or a microprocessor-based system(s). In some implementations, the one or more processors 224 and / or the system 100 includes a reduced-instruction set computer(s) (RISC), an application specific integrated circuit(s) (ASICs), a field programmable gate array(s) (FPGAs), a field programmable logic device(s) (FPLD(s)), a logic circuit(s), and / or another logic-based device executing various functions including the ones described herein. The user interface 221 , the communication interface 222, and the memory 226 may be electrically and / or communicatively coupled to the one or more processors 224.

[0054] The memory 226 may include one or more of a hard disk drive, a flash memory, a read-only memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), a random-access memory (RAM), non-volatile RAM (NVRAM) memory, a compact disk (CD), a digital versatile disk (DVD), a cache, and / or any other storage device or storage disk in which information is stored for any duration (e.g., permanently, temporarily, for extended periods of time, for buffering, for caching, etc.).

[0055] The memory 226 may include a scheduler 227. The scheduler 227 may be stored as instructions on the memory 226 and executable by the processor 224. The scheduler 227 may include a common resource schedule which is used to schedule and / or execute (e.g., by the controller 176) one or more workflows. The scheduler 227 may receivea workflow request associated with one or more working areas 304, 306 (e.g., assay bay, common resource, etc.), and schedule the workflow to a common resource schedule. The common resource schedule may be used schedule and / or execute (e.g., via controller 176) one or more workflows which utilize the second working area 306 (e.g., common resource).

[0056] As described earlier, the system 100 may include one or more consumables areas 302, 309, a first working area 304, a second working area 306, and a loading area 308. In at least some embodiments, the first working area 304 may be referred to as an assay bay (e.g., first and second assay bays) and the second working area 306 may be referred to as a common resource.

[0057] The consumable areas 302 may be used to load and store reagents and consumables needed for a library preparation process, including, disposable tips, wet or dry assay specific reagents, wet or dry bulk reagents, and reaction plates and wells. The consumables area 302 may include a consumables receptacle 310 which may include a tip tray 114 having a first tip 116 and a second tip 118, a first plate 120 having a well 122 containing a sample 124, and a second plate 126 having a well 128. In at least some embodiments, one or more of the working areas 304, 306 may include a consumables area. For example, the second working area 306 includes consumables area 309, which may include a tip tray 114 and a third plate 142 having a well 143.

[0058] The consumables receptacle 310 may be a drawer that can be pulled out from the system 100 and loaded with the consumables. The consumables receptacle 310 may also include a lid 130, an index tray 132 having a well 134 containing indexes 136, a bead tray 138 having a well 140 containing beads 141 , a liquid reservoir 312, and a dry reagent reservoir 314. One or more of these reagents 136 and / or 141 may be lyophilized and included with the dry reagent reservoir 314. In at least some aspects, one or more of the plates (e.g., plates 120, 126), the index tray 132, and / or the bead tray 138 may be stacked. The tip tray 114 may have a plurality of the first tips 116, a plurality of the second tips 118, and / or any suitable number of tips 116, 118. The tips 116, 118 may be different sizes, may be reusable for at least multiple portions of a workflow.

[0059] The system 100 may include the first working area 304, which may include a contact dispenser 145, a stage 148, a magnet 150, and a thermocycler 152. The system 100 may include the second working area 306 having an analyzer area 154 (e.g., to analyze samples), a contact dispenser 318 and a stage 320, one or more of which can operate in and / or in conjunction with the first working area 304 and the second working area 306.

[0060] The contact dispenser 145 may be movable to aspirate / dispense liquid to the consumables area 302 and / or to the first working area 304. The contact dispenser 318may be movable to aspirate / dispense liquid to the consumables area 302, to the first working area 304, and / or to the second working area 306. The contact dispenser 318 may carry one or more tips, e.g., to hold a volume of fluid.

[0061] The system 100 may include a mover 144, which in some aspects may be considered as part of the second working area 306. The mover 144 may include a robotic arm and / or include grippers. The stage 320 may carry the mover 144 and the contact dispenser 318 in some implementations. The mover 144 may include a gantry having grippers that can pick-and-place objects such as the plates 120, 126 and / or the trays 132, 138 between different areas 102, 304, 306, 308 of the system 100, e.g., the mover 144 may move the first plate 126 from the consumables area 302 to the first plate receptacle 156. The mover 144 may be implemented in different ways, however.

[0062] The stage 148 and the contact dispenser 148 may be movable to aspirate and / or dispense fluid between and above the consumables area 302 and the first working area 304 as a result. The contact dispenser 148 may, for example, move linearly, which thereby reduces the risk of cross-contamination (between different samples) and allows some or all of the tips employed in the system 300 to be reusable for at least part of the processes performed by the system 300. The stage 148 may be implemented differently, however.

[0063] The stage 148 may align the contact dispenser 145 with the tip tray 114 and the contact dispenser 145 couples with the first tip 116 from the tip tray 114. While the contact dispenser 145 is mentioned coupling with one first tip 116, the contact dispenser 145 may couple with a number of the first tips 116 that corresponds to the number of the wells 122 in the first plate 120 and / or the number of the wells 122 in the first plate 120 containing the sample 124. The wells 122 may contain different samples 124, such as a biological sample derived from a human, animal, plant, bacteria, virus, or fungi. The first tip 116 may be a smaller pipette tip that is used to move smaller fluid volumes and the second tip 118 may be a larger pipette tip that is used to move larger fluid volumes, for example. Each of the first tip 116 and / or the second tip 118 may be exposed to a single sample during a workflow reducing the likelihood of cross-contamination and reducing the need to obtain a new tip after each operation. In some library preparation workflows, for example, each of the first tip 116 and / or the second tip 118 may be used through an entire workflow. The contact dispenser 145 may couple with and / or use different ones of the tips 116, 118 depending on the workflow and / or the processes within a workflow that the system 100 is implementing.

[0064] The stage 320 may be an x-y-z stage, such that the mover 144 is movable in the x, y, and z directions. The stage 320 and the contact dispenser 318 may be movable toaspirate and / or dispense fluid between and above the consumables area 302, the first working area 304, and / or the second working area 306 as a result. The contact dispenser 148 may, for example, move linearly, which thereby reduces the risk of cross-contamination (between different samples) and allows some or all of the tips employed in the system 100 to be reusable for at least part of the processes performed by the system 100. The stage 148 may be implemented differently, however.

[0065] The second working area 306 may include a light bar 155 that may be used to degrade oligonucleotides, such as a high power ultraviolet light (UV) light bar that is regularly used throughout a workflow to repeatedly degrade oligonucleotides to deter cross contamination in some implementations.

[0066] The first working area 304 may include a first plate receptacle 156 and a second plate receptacle 158, the second working area 306 may include a third plate receptacle 159, a fourth plate receptacle 160, and a fifth plate receptacle 161 , and the analyzer area 154 may include a substrate 162 and an imaging system 164, in at least some implementations. For example, the analyzer area 154 may use the substrate 162 that is implemented by a well plate in which a portion of the sample and a dye are dispensed, and the imaging system 164 may image the portion of the sample in the well plate to determine a concentration of the sample.

[0067] The second working area 306 may include a reagent receptacle 250 having an access opening 252. A reagent reservoir 254 is shown received within the reagent reservoir 306. The first working area 304 may additionally or alternatively include a reagent receptacle 250 having an access opening 252. The reagent receptacle 250 may be refrigerated and may be a drawer that can be pulled out from the system 100 and loaded with the reagent reservoir 254. The reagent reservoir 254 may be accessed through the access opening 252 by the contact dispenser 318 to aspirate reagent from the reagent reservoir 254, for example.

[0068] The loading area 308 may be associated with loading and / or transferring a prepared sample to a system such as a sequencing system. For example, the first working area 304 may be associated with amplification processes and cleanup processes and the second working area 306 may be associated with quantification processes, library normalization processes, pooling processes, denaturing processes, and / or diluting processes. The loading area 308 may include a sipper manifold assembly 174 in the implementation shown. The sipper manifold assembly 174 may include sippers 184 to couple the sipper manifold assembly to a corresponding number of the flow cells. The sipper manifold assembly 174 may include a valve 186 to control the flow of fluid through afluidic line 188. The sipper manifold assembly 174 may include a pump 187 to selectively flow the prepared sample from a well 128, 143 through the sipper 184, through the fluidic line 188, and out of the system 100, e.g., to another system used to perform an analysis on one or more samples of interest.

[0069] The valve 186 may be implemented by a rotary valve, a pinch valve, a flat valve, a solenoid valve, a check valve, a piezo valve, etc. Other fluid control devices may prove suitable. The pump 187 may be implemented by a syringe pump, a peristaltic pump, and / or a diaphragm pump. Other types of fluid transfer devices may be used, however. The controller 176 is electrically and / or communicatively coupled to components of the system 100 to perform various functions as disclosed herein. The sipper manifold assembly 174 may alternatively be omitted.

[0070] The actuator 166 can move the magnet 150 between an upward position where the magnet 150 affects any plate positioned on the first plate receptacle 156 and a downward position where the magnet 150 does not affect any plate positioned on the first plate receptacle 156. The magnet 150 being moved relative to the first plate receptacle 156 and any plate 120, 126, 142 positioned on the first plate receptacle 156 allows less area on the first working area 304 to be consumed. The magnet 150 can moreover be moved with relatively higher confidence as compared to an alternative approach to moving one of the plates 120, 126, 142 filled with samples to a separate magnet station. The magnet 150 may be implemented by a halbach array configuration to strengthen and focus the corresponding magnetic fields.

[0071] The system 100 also includes a drive assembly 173. The drive assembly 173 includes a pump drive assembly 219 and a valve drive assembly 220. The pump drive assembly 219 may be adapted to interface with the pump 187 to pump fluid from the reagent reservoir 110 to the non-contact dispenser 146. The valve drive assembly 220 may be adapted to interface with the valve 186 to control the position of the valve 186.

[0072] More or fewer instances of the various components of the system 100 shown in FIG. 1 may be included in the system 100 (e.g., four working areas 304, three consumable areas 310, etc.).

[0073] The foregoing description is provided to enable a person skilled in the art to practice the various configurations described herein. While the subject technology has been particularly described with reference to the various figures and configurations, it should be understood that these are for illustration purposes only and should not be taken as limiting the scope of the subject technology.

[0074] As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” should be understood as not excluding plural of said elements or steps, unless such exclusion is explicitly stated. Furthermore, references to “one implementation” are not intended to be interpreted as excluding the existence of additional implementations that also incorporate the recited features. Moreover, unless explicitly stated to the contrary, implementations “comprising,” “including,” or “having” an element or a plurality of elements having a particular property may include additional elements whether or not they have that property. Moreover, the terms “comprising,” including,” having,” or the like are interchangeably used herein.

[0075] The terms “substantially," "approximately," and “about” used throughout this Specification are used to describe and account for small fluctuations, such as due to variations in processing. For example, they can refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%. In one example, these terms include situation where there is no variation - 0%.

[0076] There may be many other ways to implement the subject technology. Various functions and elements described herein may be partitioned differently from those shown without departing from the scope of the subject technology. Various modifications to these implementations may be readily apparent to those skilled in the art, and generic principles defined herein may be applied to other implementations. Thus, many changes and modifications may be made to the subject technology, by one having ordinary skill in the art, without departing from the scope of the subject technology. For instance, different numbers of a given module or unit may be employed, a different type or types of a given module or unit may be employed, a given module or unit may be added, or a given module or unit may be omitted.

[0077] Underlined and / or italicized headings and subheadings are used for convenience only, do not limit the subject technology, and are not referred to in connection with the interpretation of the description of the subject technology. All structural and functional equivalents to the elements of the various implementations described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and intended to be encompassed by the subject technology. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the above description.

[0078] It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.

Claims

CLAIMSWhat is claimed is:1 . An array of reagent cartridges for a library preparation system, the array comprising: a plurality of reagent cartridges, each reagent cartridge in the plurality of reagent cartridges having a central axis and a cross-sectional major axis and a cross-sectional minor axis, and each reagent cartridge in the plurality of reagent cartridges being configured to be accessible by a pipette of a library preparation system; wherein each reagent cartridge is spaced from an adjacent reagent cartridge in the array in an X direction and in a Y direction, and the spacings in the X direction between adjacent reagent cartridges are equal and the spacings in the Y direction between adjacent reagent cartridges are equal, but spacing between adjacent reagent cartridges in the X direction are unequal to spacings between adjacent cartridges in the Y direction.

2. The array of claim 1 , wherein the major axis of at least one reagent cartridge of the plurality of reagent cartridges is larger than the minor axis.

3. The array of any one of claims 1 or 2, wherein an aspect ratio of at least one reagent cartridge of the plurality of reagent cartridges is less than 3:1 .

4. The array of any one of claims 1 -3, wherein the aspect ratio of at least one reagent cartridge of the plurality of reagent cartridges is less than 2:1 .

5. The array of any one of claims 1 -4, wherein at least one reagent cartridge of the plurality of reagent cartridges has an oval-shaped cross-section.

6. The array of any one of claims 1 -4, wherein at least one reagent cartridge of the plurality of reagent cartridges has an ellipse-shaped cross-section.

7. The array of any one of claims 1 -4, wherein at least one reagent cartridge of the plurality of reagent cartridges has a rectangular-shaped cross-section.

8. The array of any one of claims 1 -7, wherein a first reagent cartridge of the plurality of reagent cartridges has a different shape from a second reagent cartridge of the plurality of reagent cartridges.

9. The array of any one of claims 1 -8, wherein a first reagent cartridge of the plurality of reagent cartridges has a different size from a second reagent cartridge of the plurality of reagent cartridges.

10. The array of claim 1 , wherein a first reagent cartridge of the plurality of reagent cartridges has a circular cross-sectional shape with a first diameter and a second reagent cartridge of the plurality of reagent cartridges has a second diameter, the first diameter being larger than the second diameter.11 . The array of claim 1 , wherein spacing between adjacent reagent cartridges of the plurality of reagent cartridges in the X direction is larger than spacing between adjacent reagent cartridges in the Y direction.

12. A library preparation system comprising: an assay bay, the assay bay being configured to prepare a library of samples; a consumable area including a reagent cartridge receptacle; and an array of reagent cartridges disposed in the reagent cartridge receptacle, the array or reagent cartridges comprising, a plurality of reagent cartridges, each reagent cartridge in the plurality of reagent cartridges having a central axis and a cross-sectional major axis and a cross-sectional minor axis, wherein each reagent cartridge is spaced from an adjacent reagent cartridge in the array in an X direction and in a Y direction, and the spacings in the X direction between adjacent reagent cartridges are equal and the spacings in the Y direction between adjacent reagent cartridges are equal, but spacing between adjacent reagent cartridges in the X direction are unequal to spacings between adjacent cartridges in the Y direction.

13. The library preparation system of claim 12, further comprising a pipette and each reagent cartridge in the plurality of reagent cartridges being configured to be accessible by the pipette.

14. The library preparation system of claim 13, wherein the pipette is mounted on a cross bay gantry and the pipette is movable in an X direction and a Y direction.

15. The library preparation system of one of claims 13 or 14, wherein the pipette has a plurality of pipette tips.

16. The library preparation system of any one of claims 12-15, wherein the assay bay comprises a plurality of sample wells.

17. The library preparation system of any one of claims 12-16, wherein the major axis of at least one reagent cartridge of the plurality of reagent cartridges is larger than the minor axis.

18. The library preparation system of any one of claims 12-17, wherein an aspect ratio of at least one reagent cartridge of the plurality of reagent cartridges is less than 3:1 .

19. The library preparation system of any one of claims 12-18, wherein at least one reagent cartridge of the plurality of reagent cartridges has one of an oval-shaped crosssection, an ellipse-shaped cross-section, or a rectangular-shaped cross-section.

20. The library preparation system of any one of claims 12-19, wherein spacing between adjacent reagent cartridges of the plurality of reagent cartridges in the X direction is larger than spacing between adjacent reagent cartridges in the Y direction.

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