Apparatus for managing cross-contamination in a library preparation automation platform

Abstract

Apparatus for managing cross-contamination in a library preparation automation platform are disclosed. In according with an implementation, an apparatus includes a plurality of assay bays, each having a deck defining an air drain chamber and an exhaust fan configured to draw air from the air drain chambers. A cabinet disposed above the plurality of assay bays defines and encloses a working chamber. A cabinet fan with a filter is configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure. The cabinet fan and the exhaust fans create a first airflow that flows from the working chamber and through each of the air drain chambers.

Description

APPARATUS FOR MANAGING CROSS-CONTAMINATION IN A LIBRARY PREPARATION AUTOMATION PLATFORMBACKGROUND

[0001] Current library preparation automation platforms are designed and constructed as general-purpose devices that give little or no thought to air flow management or to managing intra-bay or inter-bay cross-contamination. These platforms do not have clean, deterministic airflow in their cabinets and not much can be done to limit cross-contamination in current platforms other than to spread sources and sensitive components far from each other.SUMMARY

[0002] Advantages and benefits over the prior art as described later in this disclosure can be achieved through the provision of apparatus for managing cross-contamination in a library preparation automation platform. Various implementations of the apparatus are described below, and the apparatus, including and excluding the additional implementations enumerated below, in any combination (provided these combinations are not inconsistent), may overcome these shortcomings and achieve the benefits described herein.

[0003] In accordance with a first implementation, an apparatus comprises a plurality of assay bays, each assay bay comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber and configured to draw air from the air drain chambers. A cabinet defines and encloses a working chamber above the plurality of assay bays. A cabinet fan is positioned in the cabinet and has a filter. The cabinet fan is configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure. The cabinet fan and the exhaust fans in the plurality of assay bays create a first airflow that flows from the working chamber and through each of the air drain chambers.

[0004] In accordance with a second implementation, an apparatus comprises a plurality of assay bays, each assay bay comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber and configured to draw air from the air drain chambers. A cabinet defines and encloses a working chamber above the pluralityof assay bays. A cabinet fan is positioned in the cabinet and has a filter. The cabinet fan is configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure. Each of the plurality of assay bays comprises a movable drawer, a liquid waste receptacle mounted to the drawer, a third vent aperture extending through and transversely across a bottom of the drawer along a proximate side of the liquid waste receptacle, and a fourth vent aperture extending through and transversely across the bottom of the drawer along a distal side of the liquid waste receptacle. The cabinet fan and the exhaust fans create first airflows that flow from the working chamber and to each of the air drain chambers through the third vent apertures and the fourth vent apertures.

[0005] In accordance with a third implementation, an apparatus comprises a plurality of assay bays, each assay bay comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber and configured to draw air from the air drain chambers. A transfer bay is positioned adjacent a second side of the plurality of assay bays and comprises a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber. The exhaust fan of the transfer bay is configured to draw air from the air drain chamber of the transfer bay. A cabinet defines and encloses a working chamber above the plurality of assay bays and the transfer bay. A cabinet fan is positioned in the cabinet and has a filter. The cabinet fan is configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure. The cabinet fan, the exhaust fans of the assay bays, and the exhaust fan of the transfer bay create first airflows that flow from the working chamber and through each of the air drain chambers of the assay bays and a second airflow that flows from the working chamber and through the air drain chamber of the transfer bay.

[0006] In further accordance with the foregoing first, second, and / or third implementations, an apparatus may further include or comprise any one or more of the following:

[0007] In an implementation, the plurality of assay bays are configured for asynchronous operation.

[0008] In another implementation, the apparatus comprises a baffle extending vertically between each of the plurality of assay bays.

[0009] In another implementation, each exhaust fan comprises a filter.

[0010] In another implementation, each of the plurality of assay bays comprises a thermocycler positioned on the deck. Each deck comprises a first vent aperture extending through and transversely across a top surface of the deck and positioned along a proximate side of the thermocycler and a second vent aperture extending through and transversely across the top surface of the deck and positioned along a distal side of the thermocycler. The first airflows pass from the working chamber to each of the air drain chambers through the first vent apertures and the second vent apertures.

[0011] In another implementation, each of the plurality of assay bays comprises: a movable drawer; a liquid waste receptacle mounted to the drawer; a third vent aperture extending through and transversely across a bottom of the drawer along a proximate side of the liquid waste receptacle; and a fourth vent aperture extending through and transversely across the bottom of the drawer along a distal side of the liquid waste receptacle. The first airflows pass from the working chamber to each of the air drain chambers through the third vent apertures and the fourth vent apertures.

[0012] In another implementation, each of the plurality of assay bays comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the assay bay with the drawer in an open position.

[0013] In another implementation, each of the drawer baffles of the assay bays are movable between a first position with the drawer in a closed position and a second position with the drawer in the open position.

[0014] In another implementation, the apparatus comprises a consumables bay positioned adjacent a first side of the plurality of assay bays. The working chamber extends above the consumables bay. A baffle extends vertically between the consumables bay and an adjacent assay bay.

[0015] In another implementation, the apparatus comprises a transfer bay positioned adjacent a second side of the plurality of assay bays. The working chamber extends above the transfer bay. The transfer bay comprises a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber of the transfer bay, the exhaust fan of the transfer bay configured to draw air from the air drain chamber of the transfer bay. The cabinet fan and the exhaust fan in the transfer bay create a second airflow that flows from the working chamber and through the air drain chamber of the transfer bay.

[0016] In another implementation, the apparatus comprises a baffle extending vertically between the transfer bay and an adjacent assay bay.

[0017] In another implementation, the transfer bay comprises a quant station positioned on the deck. The deck comprises a fifth vent aperture extending through and transversely across a top surface of the deck and positioned along a proximate side of the quant station and a sixth vent aperture extending through and transversely across the top surface of the deck and positioned along a distal side of the quant station. The second airflow passes from the working chamber to the air drain chamber of the transfer bay through the fifth vent aperture and the sixth vent aperture.

[0018] In another implementation, the transfer bay comprises: a movable drawer; a liquid waste receptacle mounted to the drawer; a seventh vent aperture extending through and transversely across a bottom of the drawer along a proximate side of the liquid waste receptacle; and an eighth vent aperture extending through and transversely across the bottom of the drawer along a distal side of the liquid waste receptacle. The second airflow passes from the working chamber to the air drain chamber of the transfer bay through the seventh vent aperture and the eighth vent aperture.

[0019] In another implementation, the transfer bay comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the transfer bay with the drawer in an open position.

[0020] In another implementation, the drawer baffle of the transfer bay is movable between a first position with the drawer in a closed position and a second position with the drawer in the open position

[0021] 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 and / or may be combined to achieve the particular benefits of a particular aspect. 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.BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG. 1 illustrates a front perspective view of an implementation of an apparatus for managing cross-contamination in a library preparation automation platform;

[0023] FIG. 2 illustrates a top view of the apparatus of Fig. 1 ;

[0024] FIG. 3 illustrates a side view of an implementation of an assay bay of the apparatus of Fig. 1 with a drawer in a closed position;

[0025] FIG. 4 illustrates a top view of the assay bay of Fig. 3;

[0026] FIG. 5 illustrates the assay bay of Fig. 3 with the drawer in an open position;

[0027] FIG. 6 illustrates a side view of an implementation of a consumables bay of the apparatus of Fig. 1 with a drawer in a closed position;

[0028] FIG. 7 illustrates the consumables bay of Fig. 6 with the drawer in an open position;

[0029] FIG. 8 illustrates a side view of an implementation of a transfer bay of the apparatus of Fig. 1 with a drawer in a closed position;

[0030] FIG. 9 illustrates a top view of the transfer bay of Fig. 8;

[0031] FIG. 10 illustrates the transfer bay of Fig. 8 with the drawer in an open position; and

[0032] FIG. 1 1 illustrates a schematic diagram of an implementation of a system that can use the apparatus of Fig. 1 .DETAILED DESCRIPTION

[0033] Although the following text discloses a detailed description of implementations of apparatus, 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 can 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.

[0034] In the implementations shown and discussed herein, the library preparation automation platform has multiple assay bays and can execute multiple Next-Generation Sequencing (NGS) Library Preparation Assays in parallel and enable random start (asynchronous operation) of the assay bays. The platform consolidates all steps of the workflow into a single, uninterrupted, automated workflow intended for execution in a Post- Polymerase Chain Reaction (PCR) space, which differs from the historical practice of running the first part of a workflow in a Pre-PCR lab space and the second part of the workflow in a separate Post-PCR lab space.

[0035] Running multiple, asynchronous assays with uninterrupted workflows can increase the risk of cross-contamination between samples, includes contamination between adjacent bays (inter-bay) and within a bay (intra-bay). Once cause of inter-bay and intra-bay crosscontamination is aerosolized transfer of liquid containing sample, such as from jet dispensing liquid waste, jetting a sample at a working plate (e.g., during bead cleanup operations), tip ejection to waste, negative pressure spikes on working wells during lid removal, shocks to a working plate during working plate transfer, etc. To manage possible cross-contamination, the disclosed library preparation automation platform creates airflows around elements that may cause aerosolized contamination to manage intra-bay cross-contamination and can also include baffles between each bay to manage inter-bay cross-contamination.

[0036] Referring to Figs. 1 -2, an illustration is shown of an implementation of an apparatus 100, which as shown is a library preparation automation platform that manages crosscontamination. Apparatus 100 can be used to automatically, easily, and efficiently prepare DNA libraries for sequencing applications. Apparatus 100 may perform DNA library preparation workflows that include amplification processes, cleanup processes, quantification processes, library normalization processes, pooling processes, denaturing processes, diluting processes, etc., and can perform a number of workflows at the same time and / or at different times. In this implementation, apparatus 100 generally includes a cabinet 102, a plurality of assay bays 200 that can be configured for asynchronous operation, at least one consumables bay 300, and at least one transfer bay 400.

[0037] Cabinet 102 generally includes a base 104, a frame 106 mounted to base 104, and walls 108 (e.g., a front wall, back wall, side walls, and top wall). Walls 108 of cabinet 102 e.g., glass walls, plexiglass walls, sheet metal walls, etc.) together with base 104 and frame 106 define and enclose a substantially airtight working chamber 1 10 that extends above assay bays 200, consumables bay 300, and transfer bay 400. A cabinet fan 112 is positioned in cabinet 102 e.g., in a top wall, front wall, and / or side wall of cabinet 102) and is dynamically configured to deliver air from external of cabinet 102 into working chamber 110 to keep working chamber 110 at a neutral pressure {e.g., approximately atmospheric pressure) or a positive pressure {e.g., slightly above atmospheric pressure) to assist in creating first airflows 250 and a second airflow 450 through apparatus 100 in conjunction with exhaust fans 206, 406, as discussed below. In alternative implementations, cabinet 102 can have multiple cabinet fans 112 {e.g., one cabinet fan 112 for each assay bay 200, consumables bay 300, and transfer bay 400). Cabinet fan 1 12 can also have a filter 114 {e.g., a high efficiency particulate air (HEPA) filter) and a diffuser to prevent air from being blown directly onto materials in assay bay(s) 200, consumables bay(s) 300, and transfer bay(s) 400.

[0038] A cross-bay gantry 122 can be secured to base 104 and positioned within working chamber 110. Cross-bay gantry 122 can include a contact dispenser 124 that is movable in the X, Y, and Z directions and is configured to aspirate / dispense liquid between locationswithin assay bays 200, between locations within consumables bay 300, between locations within transfer bay 400, and / or to locations between assay bays 200, consumables bay 300, and transfer bay. Cross-bay gantry 122 can also include a large volume pipettor, a small volume pipettor, a robotic arm and / or grippers (not shown) that can pick-and-place objects, such as plates and / or the trays, between different locations, a configuration verification camera, a sterilization light, a tip movement system, etc.

[0039] Apparatus 100 can also include baffles 1 16 (e.g., glass panels, plexiglass panels, sheet metal panels, etc.) that each extend vertically from base 104 and are positioned between each of the plurality of assay bays 200, between consumables bay 300 and an adjacent assay bay 200, and between transfer bay 400 and an adjacent assay bay 200. Baffles 116 can be used to reduce or prevent inter-bay cross contamination by limiting airflow between assay bays 200, consumables bay 300, and transfer bay 400, thereby reducing or eliminating aerosolized contaminates from being communicated between adjacent bays.

[0040] Referring to Figs. 3-5, an implementation of an assay bay 200 of apparatus 100 is shown. Each assay bay 200 includes a deck 202 that defines an enclosed air drain chamber 204 located underneath a top surface 212 of deck 202. An exhaust fan 206 is in fluid communication with air drain chamber 204 and is configured to dynamically draw air from air drain chamber 204 and exhaust the air from air drain chamber 204 to an area external of cabinet 102. Each exhaust fan 206 can also have a filter 208 e.g., a HEPA filter), to prevent contamination of the ambient air external of cabinet 102. Cabinet fan 112 and exhaust fans 206 in the plurality of assay bays 200 can each be dynamically controlled to keep working chamber 110 at a neutral to positive pressure and create first airflows 250 that flow from working chamber 110 and through each air drain chamber 204. First airflows 250 can reduce intra-bay cross-contamination in assay bays 200 by carrying possible aerosolized contaminates from a source of the aerosolized contaminate and out of working chamber 1 10 and exhausting the aerosolized contaminates through air drain chambers 204 via exhaust fans 206, rather than allowing the aerosolized contaminates to possibly contamination other locations in assay bay 200. For example, during times where increased aerosolizedcontamination may be possible (e.g., during the ejection of liquid, during the ejection of tips, when transferring samples from one plate to another, when the lid is removed from the working plate after the thermocycler, etc.) the fan speed of cabinet fan 1 12 and exhaust fan(s) 206 can be increased to increase first airflow(s) 250 and remove possible aerosolized contaminates more efficiently. In addition, when a front door of cabinet 102 or movable drawers 220, 420 are opened, the fan speed of cabinet fan 112 can be increased to increase the positive pressure in working chamber 1 10 and prevent external air from entering cabinet 102.

[0041] Each assay bay 200 has a thermocycler 214 positioned on deck 202. Thermocycler 214 can include a stage 215 that is movable in the X and Z directions (but not in the Y direction) and that is movable to aspirate and / or dispense fluid within thermocycler 214. Thermocycler 214 can be a key risk source for aerosolized contamination as it is where samples are amplified, liquid handling events are focused, and lid and plate loading / unloading events occur. To provide first airflow 250 around thermocycler 214 and remove aerosolized particulates generated by operation of thermocycler 214, deck 202 includes a first vent aperture 216 and a second vent aperture 218. First vent aperture 216 extends through and transversely across top surface 212 of deck 202 and is positioned along a proximate side of thermocycler 214. Second vent aperture 218 extends through and transversely across top surface 212 and is positioned along a distal side of thermocycler 214. As used herein, the term proximate side means the side closer to a front 1 18 of apparatus 100 and distal side means the side closer to a rear 120 of apparatus 100. First vent aperture 216 and second vent aperture 218 allow first airflow 250 to pass from working chamber 1 10, around thermocycler 214, and into air drain chamber 204 through first vent aperture 216 and second vent aperture 218 to carry possible aerosolized contaminates generated by thermocycler 214 out of working chamber 110 and exhausting the aerosolized contaminates through air drain chambers 204 via exhaust fans 206, rather than allowing the aerosolized contaminates to possibly contamination other locations in assay bay 200.

[0042] Each assay bay 200 also includes a pipette assembly 246 that is movable in the Y and Z directions and is configured to aspirate / dispense liquid between locations within the particular assay bay 200.

[0043] In the implementation shown, each assay bay 200 also includes a movable drawer 220 that is movably mounted to deck 202 and is movable between a closed position (Fig. 3) and an open position (Fig. 5). In the closed position, deck 202 and movable drawer 220 essentially separate air drain chamber 204 from working chamber 110. In the open position, movable drawer 220 can be loaded with and store consumables, such as large liquid reagents 230, small liquid reagents 232, Lyo reagents 234, sample plates 236 (e.g., sample plates, reaction plates and wells, etc.), disposable tips 238, etc., that may be needed for a library preparation process on a bottom 222 of movable drawer 220. Movable drawer 220 also includes a liquid waste receptacle 224 and a tip waste receptacle 240 mounted to bottom 222 of movable drawer 220. A top surface of liquid waste receptacle 224 and tip waste receptacle 240 is preferably located below a critical contamination plane 244, which is a plane located at the height at which an aerosolized particle could enter a sample or reagent well.

[0044] To allow first airflow 250 to flow around liquid waste receptacle 224 and remove airborne particulates generated by exhausting liquid into liquid waste receptacle 224, movable drawer 220 includes a third vent aperture 226 and a fourth vent aperture 228. Third vent aperture 226 extends through and transversely across bottom 222 of movable drawer 220 and is positioned along a proximate side of liquid waste receptacle 224. Fourth vent aperture 228 extends through and transversely across bottom 222 of movable drawer 220 and is positioned along a distal side of liquid waste receptacle 224. Third vent aperture 226 and fourth vent aperture 228 allow first airflow 250 to pass from working chamber 1 10, around liquid waste receptacle 224, and into air drain chamber 204 through third vent aperture 226 and fourth vent aperture 228 to carry possible aerosolized contaminates generated by exhausting liquid into liquid waste receptacle 224 out of working chamber 110 and exhausting the aerosolized contaminates through air drain chambers 204 via exhaust fans 206, rather than allowing the aerosolized contaminates to possibly contamination other locations in assay bay 200.

[0045] As discussed above, assay bays 200 can be configured for asynchronous operation and, therefore, movable drawers 220 of assay bays 200 can be opened at different times. Therefore, the first airflow 250 through air drain chambers 204 of assay bays 200 should be managed when a movable drawer 220 is moved into the open position. To substantially limit external airflow into air drain chamber 204 when movable drawer 220 is moved into the open position (Fig. 5), each assay bay 200 can include a drawer baffle 242 that is movable between a first position with movable drawer 220 in the closed position (Fig. 3) and a second position with movable drawer 220 in the open position (Fig. 5), to substantially block external airflow into air drain chamber 204. For example, drawer baffle 242 could be a plate that is motorized or is biased into the second position by spring hinge when movable drawer 220 is in the open position, thereby substantially blocking external airflow into air drain chamber 204. If motorized, drawer baffle 242 could be moved into the first position when movable drawer 220 is closed. Alternatively, if not motorized, when movable drawer 220 is closed, drawer baffle 242 could be moved into the first position by tip waste receptacle 240, which extends below bottom 222 of movable drawer 220 and can engage drawer baffle 242 and move drawer baffle 242 to the first position.

[0046] Referring to Figs. 6-7, an implementation of a consumables bay 300 of apparatus 100 is shown. Consumables bay 300 includes a deck 302 and can be positioned adjacent a first side of the plurality of assay bays 200. In the implementation shown, consumables bay 300 also includes a movable drawer 320 that is movably mounted to deck 302 and is movable between a closed position (Fig. 6) and an open position (Fig. 7). In the open position, movable drawer 320 can be bulk loaded with and store consumables, preferably only noncontamination risk consumables, such as sample plates 336 (e.g., quant plates, work plates, etc.), disposable tips 338, etc., that may be needed for a library preparation process on a bottom 322 of movable drawer 320. In the closed position, the stored consumables can be accessed in consumables bay 300 by cross-bay gantry 122 for use in assay bays 200 and / or transfer bay 400, as required.

[0047] Referring to Figs. 8-10, an implementation of a transfer bay 400 of apparatus 100 is shown, which can be used for loading and / or transferring a prepared sample to a system such as a sequencing system and / or next generation sequencing system. Transfer bay 400 can be positioned adjacent a second side of the plurality of assay bays 200, opposite consumables bay 300 on the first side. Transfer bay 400 includes a deck 402 that defines an enclosed air drain chamber 404 located underneath a top surface 412 of deck 402. An exhaust fan 406 is in fluid communication with air drain chamber 404 and is configured to dynamically draw air from air drain chamber 404 and exhaust the air from air drain chamber 404 to an area external of cabinet 102. Each exhaust fan 406 can also have a filter 408 (e.g., a HEPA filter), to prevent contamination of the ambient air external of cabinet 102. Cabinet fan 112 and exhaust fan 406 in transfer bay 400 can each be dynamically controlled to keep working chamber 1 10 at a neutral to positive pressure and create a second airflow 450 that flow from working chamber 1 10 and through air drain chamber 404. Second airflow 450 can reduce intra-bay cross-contamination in transfer bay 400 by carrying possible aerosolized contaminates from a source of the aerosolized contaminate and out of working chamber 1 10 and exhausting the aerosolized contaminates through air drain chamber 404 via exhaust fan 406, rather than allowing the aerosolized contaminates to possibly contamination other locations in transfer bay 400. For example, during times where increased aerosolized contamination may be possible e.g., during the ejection of liquid, during the ejection of tips, when transferring samples from one plate to another, when the lid is removed from the working plate after the thermocycler, etc.) the fan speed of cabinet fan 1 12 and exhaust fan(s) 406 can be increased to increase second airflow(s) 450 and remove possible aerosolized contaminates more efficiently. In addition, when a front door of cabinet 102 or movable drawers 220, 420 are opened, the fan speed of cabinet fan 112 can be increased to increase the positive pressure in working chamber 110 and prevent external air from entering cabinet 102.

[0048] Transfer bay 400 has a quant station 414 positioned on deck 402. To provide second airflow 450 around quant station 414 and remove aerosolized particulates generatedby operation of quant station 414, deck 402 includes a fifth vent aperture 416 and a sixth vent aperture 418. Fifth vent aperture 416 extends through and transversely across top surface 412 of deck 402 and is positioned along a proximate side of quant station 414. Sixth vent aperture 418 extends through and transversely across top surface 412 and is positioned along a distal side of quant station 414. Fifth vent aperture 416 and sixth vent aperture 418 allow second airflow 450 to pass from working chamber 1 10, around quant station 414, and into air drain chamber 404 through fifth vent aperture 416 and sixth vent aperture 418 to carry possible aerosolized contaminates generated by quant station 414 out of working chamber 1 10 and exhausting the aerosolized contaminates through air drain chamber 404 via exhaust fan 406, rather than allowing the aerosolized contaminates to possibly contamination other locations in transfer bay 400.

[0049] In the implementation shown, transfer bay 400 could also include a movable drawer 420 that is movably mounted to deck 402 and is movable between a closed position (Fig. 8) and an open position (Fig. 10). In the closed position, deck 402 and movable drawer 420 essentially separate air drain chamber 404 from working chamber 1 10. In the open position, movable drawer 420 can be loaded with and store consumables, such as D&D Pool Strips 437, disposable tips 438, etc., that may be needed for a library preparation process on a bottom 422 of movable drawer 420. Movable drawer 220 can also include adjustable receivers that can be used to receive multiple waste plates 436, a liquid waste receptacle 424, and a tip waste receptacle 440 mounted to bottom 422 of movable drawer 420. A top surface of liquid waste receptacle 424 and tip waste receptacle 440 is preferably located below a critical contamination plane 444, which is a plane located at the height at which an aerosolized particle could enter a sample or reagent well. In alternative implementations, transfer bay 400 may not have a movable drawer 420 and the consumables, adjustable receivers, liquid waste receptacle, and / or tip waste receptacle could be loaded / mounted on deck 402 of transfer bay 400.

[0050] To allow second airflow 450 to flow around liquid waste receptacle 424 and remove airborne particulates generated by exhausting liquid into liquid waste receptacle 424, movabledrawer 420 includes a seventh vent aperture 426 and an eighth vent aperture 428. Seventh vent aperture 426 extends through and transversely across bottom 422 of movable drawer 420 and is positioned along a proximate side of liquid waste receptacle 424. Eighth vent aperture 428 extends through and transversely across bottom 422 of movable drawer 420 and is positioned along a distal side of liquid waste receptacle 424. Seventh vent aperture 426 and eighth vent aperture 428 allow second airflow 450 to pass from working chamber 110, around liquid waste receptacle 424, and into air drain chamber 404 through seventh vent aperture 426 and eighth vent aperture 428 to carry possible aerosolized contaminates generated by exhausting liquid into liquid waste receptacle 424 out of working chamber 1 10 and exhausting the aerosolized contaminates through air drain chamber 404 via exhaust fan 406, rather than allowing the aerosolized contaminates to possibly contamination other locations in transfer bay 400.

[0051] Second airflow 450 through air drain chamber 404 of transfer bay 400 can also be managed when movable drawer 420 is moved into the open position. To substantially limit external airflow into air drain chamber 404 when movable drawer 420 is moved into the open position (Fig. 8), transfer bay 400 can include a drawer baffle 442 that is movable between a first position with movable drawer 420 in the closed position (Fig. 8) and a second position with movable drawer 420 in the open position (Fig. 10), to substantially block external airflow into air drain chamber 404. For example, drawer baffle 442 could be a plate that is motorized or is biased into the second position by spring hinge when movable drawer 420 is in the open position, thereby substantially blocking external airflow into air drain chamber 404. If motorized, drawer baffle 442 could be moved into the first position when movable drawer 420 is closed. Alternatively, if not motorized, when movable drawer 420 is closed, drawer baffle 442 could be moved into the first position by tip waste receptacle 440, which extends below bottom 422 of movable drawer 420 and can engage drawer baffle 442 and move drawer baffle 442 to the first position.

[0052] Cabinet fan 1 12, exhaust fans 206 of assay bays 200, and exhaust fan 406 of transfer bay 400 can also be communicatively connected to a controller (not shown) that isconfigured to control cabinet fan 112, exhaust fans 206, and exhaust fan 406 to keep working chamber 110 at the positive pressure and assist in creating first airflows 250 and a second airflow 450 through apparatus 100. The controller can include a user interface, a communication interface, one or more processors, and a memory storing instructions executable by the one or more processors to perform the various functionality discussed herein. The user interface, the communication interface, and the memory are electrically and / or communicatively coupled to the one or more processors. The user interface can receive inputs from a user and provide information to the user associated with the operation of apparatus 100. The user interface can include a touch screen, a display, a keyboard, 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). The communication interface can enable communication between apparatus 100 and a remote system(s) (e.g., computers) using a network(s). The network(s) may include an intranet, a local-area network (LAN), a wide-area network (WAN), the intranet, etc. The one or more processors can include one or more of a processor-based system(s) or a microprocessor-based system(s). In some implementations, the one or more processors can include 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. The memory can 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 randomaccess 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).

[0053] Referring to Fig. 11 , a schematic diagram of an implementation of a system 500 for managing cross-contamination in a library preparation platform, in accordance with the apparatus of Fig. 1 and the teachings of this disclosure. System 500 may be used toautomatically, easily, and efficiently prepare DNA libraries for sequencing applications. System 500 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, etc. 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.

[0054] System 500 may include a controller 502, which may be electrically and / or communicatively coupled to one or more components of the system 500 to perform various functions as described herein. Controller 502 may include a user interface 504, a communication interface 506, one or more processors 508, and a memory 510 storing instructions executable by the one or more processors 508 to perform the various functionalities described herein.

[0055] User interface 504 may receive input from a user, and provide information to the user associated with the operation of system 500 (e.g., information about the workflows being scheduled and / or taking place). User interface 504 may include a touch screen, a display, a keyboard, a speaker(s), a mouse, a track ball, a voice recognition system, etc. The touch screen and / or the display may display a graphical user interface (GUI).

[0056] Communication interface 506 can enable communication between system 500 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 system 500, such as scheduling one or more workflows.

[0057] System 500 may include one or more processors 508 and / or processor-based system(s) or a microprocessor-based system(s). In some implementations, processor(s) 508 and / or system 500 may include 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 deviceexecuting various functions including the ones described herein. User interface 504, communication interface 506, and memory 510 may be electrically and / or communicatively coupled to processor(s) 508.

[0058] Memory 510 may include one or more of a hard disk drive, a flash memory, a readonly 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.).

[0059] Memory 510 may include a scheduler 512, which may be stored as instructions on memory 510 and executable by processor 508. Scheduler 512 may include a common resource schedule which is used to schedule and / or execute e.g., by controller 502) one or more workflows. Scheduler 512 may receive a workflow request associated with one or more working areas 516, 518 e.g., assay bay 200, transfer bay 400, 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 502) one or more workflows which utilize the second working area 518 {e.g., transfer bay 400). Scheduler 512 or another suitable component {e.g., processor 508) may be configured to determine one or more conflicts in time and / or space with respect to second working area 518 for at least two workflows associated with respective working areas 516, as further described herein. While scheduler 512 is described as scheduling new workflows to a common resource schedule, in at least some aspects scheduler 512 may also evaluate an existing workflow schedule and / or common resource schedule, to make optimizations and the like, as one having skill in the art will appreciate.

[0060] System 500 may include one or more consumables areas 514 {e.g., consumables bay 300), one or more first working areas 516 {e.g., assay bays 200), a second working area 518 {e.g., transfer bay 400), and a loading area 520.

[0061] The consumable area 514 may be used to load and store reagents and consumables needed for a library preparation process, including, disposable tips (e.g., disposable tips 338), wet or dry assay specific reagents, wet or dry bulk reagents, and reaction plates and wells e.g., sample plates 336), etc. Consumables area 514 may include a consumables receptacle 522 which may include a tip tray 524 having a first tip 526 and a second tip 528, a first plate 530 having a well 532 containing a sample 534, and a second plate 536 having a well 538. In at least some embodiments, one or more of the working areas 516, 518 may include a consumables area.

[0062] The consumables receptacle 522 may be a drawer e.g., movable drawer 270) that can be pulled out from system 500 and loaded with consumables 524, 526, 528, 530, 536. Consumables receptacle 522 may also include a lid 540, an index tray 542 having a well 544 containing indexes 546, a bead tray 548 having a well 550 containing beads 552, a liquid reservoir 554, and a dry reagent reservoir 556. One or more reagents 546 and / or 552 may be lyophilized and included with the dry reagent reservoir 556. In at least some aspects, one or more of the plates {e.g., plates 530, 536), index tray 542, and / or bead tray 548 may be stacked. Tip tray 524 may have a plurality of the first tips 526, a plurality of the second tips 528, and / or any suitable number of tips 526, 528. Tips 526, 528 may be different sizes and may be reusable for at least multiple portions of a workflow.

[0063] First working area 516 may include a contact dispenser 558, a stage 560, a magnet 562, and a thermocycler 564. Second working area 518 may include an analyzer area 566 {e.g., to analyze samples), a contact dispenser 568 and a stage 570, one or more of which can operate in and / or in conjunction with first working area 516 and second working area 518.

[0064] Contact dispenser 558 may be movable to aspirate / dispense liquid to consumables area 514 and / or to first working area 516. Contact dispenser 568 may be movable to aspirate / dispense liquid to consumables area 514, to first working area 516, and / or to second working area 518. Contact dispenser 568 may carry one or more tips, e.g., to hold a volume of fluid.

[0065] System 500 may include a mover 572, which in some aspects may be considered as part of second working area 518. Mover 572 may include a robotic arm and / or include grippers. Stage 570 may carry mover 572 and contact dispenser 568 in some implementations. Mover 572 may include a gantry having grippers that can pick-and-place objects such as plates 530, 536 and / or trays 542, 548 between different areas 516, 518, 520 of system 500, e.g., mover 572 may move first plate 530 from consumables area 514 to first plate receptacle 574. Mover 572 may be implemented in different ways, however.

[0066] Stage 560 may be an X-Z stage, such that stage 560 is movable in the X and Z directions (but not in the Y direction). Stage 560 and contact dispenser 558 may be movable to aspirate and / or dispense fluid between and above consumables area 514 and first working area 516 as a result. Contact dispenser 558 may, for example, move linearly in the X direction, which thereby reduces the risk of cross-contamination (between different samples) and allows some or all of the tips employed in system 500 to be reusable for at least part of the processes performed by system 500. Stage 560 may be implemented differently, however.

[0067] Stage 560 may align contact dispenser 558 with tip tray 524 and contact dispenser 558 couples with first tip 526 from tip tray 524. While contact dispenser 558 is mentioned coupling with one first tip 526, contact dispenser 558 may couple with a number of first tips 526 that corresponds to the number of wells 532 in first plate 530 and / or the number of wells 532 in first plate 530 containing sample(s) 534. Wells 532 may contain different samples 534, such as a biological sample derived from a human, animal, plant, bacteria, virus, or fungi. First tip 526 may be a smaller pipette tip that is used to move smaller fluid volumes and second tip 528 may be a larger pipette tip that is used to move larger fluid volumes. Each of first tip 526 and / or second tip 528 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, each of first tip 526 and / or second tip 528 may be used through an entire workflow. Contact dispenser 558 may couple with and / or use different ones of tips 526, 528 depending on the workflow and / or the processes within a workflow that system 500 is implementing.

[0068] Stage 570 may be an X-Y-Z stage, such that mover 572 is movable in the X, Y, and Z directions. Stage 570 and contact dispenser 568 may be movable to aspirate and / or dispense fluid between and above consumables area 514, first working area 516, and / or second working area 518 as a result. Contact dispenser 568 may, for example, move linearly in the X direction, which thereby reduces the risk of cross-contamination (between different samples) and allows some or all of the tips employed in system 500 to be reusable for at least part of the processes performed by system 500. However, stage 560 may be implemented differently.

[0069] Second working area 518 may include a light bar 576 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.

[0070] First working area 516 may include a first plate receptacle 574 and a second plate receptacle 578, second working area 518 may include a third plate receptacle 580, a fourth plate receptacle 582, and a fifth plate receptacle 584, and analyzer area 566 may include a substrate 586 and an imaging system 588, in at least some implementations. For example, analyzer area 566 may use substrate 586 that is implemented by a well plate in which a portion of the sample and a dye are dispensed, and imaging system 588 may image the portion of the sample in the well plate to determine a concentration of the sample.

[0071] Second working area 518 may include a reagent receptacle 590 having an access opening 592. A reagent reservoir 594 is shown received within reagent receptacle 590. First working area 516 may additionally or alternatively include a reagent receptacle having an access opening. Reagent receptacle 590 may be refrigerated and may be a drawer that can be pulled out from system 500 and loaded with reagent reservoir 594. Reagent reservoir 594 may be accessed through access opening 592 by contact dispenser 568 to aspirate reagent from reagent reservoir 594.

[0072] Loading area 520 may be associated with loading and / or transferring a prepared sample to a system such as a sequencing system. For example, first working area 516 maybe associated with amplification processes and cleanup processes and second working area 518 may be associated with quantification processes, library normalization processes, pooling processes, denaturing processes, and / or diluting processes. Loading area 520 may include a sipper manifold assembly 596 in the implementation shown. Sipper manifold assembly 596 may include sippers 598 to couple sipper manifold assembly 596 to a corresponding number of flow cells. Sipper manifold assembly 596 may include a valve 600 to control the flow of fluid through a fluidic line 602. Sipper manifold assembly 596 may include a pump 604 to selectively flow the prepared sample from a well 538, 606 through sipper 598, through fluidic line 602, and out of system 500, e.g., to another system used to perform an analysis on one or more samples of interest.

[0073] Valve 600 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. Pump 604 may be implemented by a syringe pump, a peristaltic pump, and / or a diaphragm pump. Other types of fluid transfer devices may be used. Controller 502 is electrically and / or communicatively coupled to components of system 500 to perform various functions as disclosed herein. Sipper manifold assembly 596 may alternatively be omitted.

[0074] An actuator 608 can move magnet 562 between an upward position where magnet 562 affects any plate positioned on first plate receptacle 574 and a downward position where magnet 562 does not affect any plate positioned on first plate receptacle 574. Magnet 562 being moved relative to first plate receptacle 574 and any plate 530, 536, 610 positioned on first plate receptacle 574 allows less area on first working area 516 to be consumed. Magnet 562 can moreover be moved with relatively higher confidence as compared to an alternative approach to moving one of the plates 530, 536, 610 filled with samples to a separate magnet station. Magnet 562 may be implemented by a Halbach array configuration to strengthen and focus the corresponding magnetic fields.

[0075] In one example workflow, stage 560 aligns contact dispenser 558 with index tray 542 and contact dispenser 558 aspirates indexes 546 from index tray 542 using first tip 526. Stage 560 can then align contact dispenser 558 with first plate 530 and contact dispenser 558dispenses indexes 546 into well 532 of first plate 530. Mover 572 moves lid 540 from consumables area 514 and places lid 540 on first plate 530 to cover well 532 of first plate 530 with lid 540. First working area 516 also includes a lid 612 and an actuator 614. Lid 612 may be referred to as a cover and / or a door. Actuator 614 may move lid 612 in operation relative to plate receptacle 578, for example, to cover plate receptacle 578 during amplification processes. Lid 612 may thus be positioned to enclose first plate 530 during the amplification processes. Lid 540 and / or lid 612 may enclose first plate 530 during the amplification processes.

[0076] Thermocycler 564 is aligned with first plate receptacle 578 and thermocycler 564 amplifies sample 534 within well 532 of first plate 530. Thermocycler 564 and / or magnet 562 can act on a plate 530, 536 received at first plate receptacle 578 in the implementation shown. Thermocycler 564 may alternatively be spaced from magnet 562.

[0077] Actuator 614 can move lid 612 off of first plate 530 and / or mover 572 can move lid 540 from first plate 530 to consumables area 514 after the amplification processes are complete. Consumables area 514 includes a waste 616 that can receive used consumables such as, for example, lid 540. Lid 540 may alternatively be reused. Waste 616 may be a waste tray having an absorbent material to absorb liquid waste.

[0078] System 500 may perform cleanup processes, according to one or more workflows, after the amplification processes are performed. Stage 560 aligns contact dispenser 558 with bead tray 548 and contact dispenser 558 aspirates beads 552 from bead tray 548. Contact dispenser 558 may aspirate beads 552 using the same first tip 526 used to aspirate indexes 546. Contact dispenser 558 may alternatively use another one of first tips 526 or one of second tips 528 to aspirate beads 552.

[0079] Stage 560 aligns contact dispenser 558 with first plate 530 and contact dispenser 558 dispenses beads 552 into well 532 of first plate 530 as part of the cleanup process. Stage 560 aligns contact dispenser 558 with liquid reservoir 554 and contact dispenser 558 aspirates first reagent 618 from liquid reservoir 554. Stage 560 then aligns contact dispenser 558 with first plate 530 and contact dispenser 558 dispenses first reagent 618 into well 532 of first plate530. Contact dispenser 558 may alternatively aspirate hydrating liquid 620 from liquid reservoir 554 and then dispense hydrating liquid 620 into dried reagent 622 contained within dry reagent reservoir 556 to rehydrate dried reagent 622 and form first reagent 618. Contact dispenser 558 may pipette mix dried reagent 622 and hydrating liquid 620. First reagent 618 may be a bead buffer and sample 534 may bind to beads 552 in the presence of the bead buffer. Contact dispenser 558 may be able to jet dispense with adequate liquid velocity to enable jet mixing in some implementations. System 500 may also include a shaker to enable mixing.

[0080] Stage 560 aligns contact dispenser 558 with tip tray 524 and contact dispenser 558 places first tip 526 in tip tray 524 and contact dispenser 558 then couples with second tip 528 from tip tray 524. While contact dispenser 558 is mentioned coupling with one second tip 528, contact dispenser 558 may couple with a number of second tips 528 that corresponds to the number of wells 532 in first plate 530 and / or the number of wells 532 in first plate 530 containing the sample 534.

[0081] Actuator 608 moves magnet 562 toward plate receptacle 578 and magnet 562 draws beads 552 toward magnet 562. Beads 552 and sample 534 bound to beads 552 may be positioned toward the bottom of well 532 of first plate 530 or on a side(s) of well 532. Tips 526 and / or 528 may easily access well 532 if beads 552 are on the side of well 532. Magnet 562 may cause beads 552 to be in any position within well 532.

[0082] Stage 560 aligns contact dispenser 558 with first plate 530 and contact dispenser 558 aspirates first reagent 618 from well 532 of first plate 530. Contact dispenser 558 may dispense first reagent 618 aspirated from well 532 of first plate 530 into waste 616.

[0083] Stage 560 aligns contact dispenser 558 with liquid reservoir 554 and contact dispenser 558 aspirates second reagent 624 from liquid reservoir 554 and stage 560 then aligns contact dispenser 558 with first plate 530 and contact dispenser 558 dispenses second reagent 624 into well 532 of first plate 530. Contact dispenser 558 may alternatively aspirate hydrating liquid 620 from liquid reservoir 554 and then dispense hydrating liquid 620 into a dried reagent 626 contained within dry reagent reservoir 556 to rehydrate dried reagent 626and form second reagent 624. Second reagent 624 may be an elution buffer that releases sample 534 from being bound to beads 552 and, specifically, releases DNA associated with sample 534 from being bound to beads 552.

[0084] Mover 572 moves second plate 536 from consumables area 514 to second plate receptacle 578. System 500 can use second plate 536 for a transfer operation. Second plate 536 may alternatively remain in consumables area 514 during the transfer operation. Actuator 608 moves magnet 562 toward second plate receptacle 578 to draw beads 552 toward magnet 562 and, thus, provide a substantially bead-free eluate solution comprising second reagent 624 and sample 534 within well 532.

[0085] Stage 560 can align contact dispenser 558 with first plate 530 and contact dispenser 558 aspirates second reagent 624 and sample 534 from well 532 of first plate 530 using second tip 528. Stage 560 aligns contact dispenser 558 with second plate 536 and contact dispenser 558 dispenses second reagent 624 and sample 534 into well 538 of second plate 536. Second plate 536 may alternatively be positioned in consumables area 514 when contact dispenser 558 dispenses second reagent 624 and sample 534 into well 538 of second plate 536. Second plate receptacle 578 may be omitted from second working area 518 in such implementations.

[0086] System 500 may perform the quantification processes, according to one or more workflows, after the cleanup processes are performed. Mover 572 moves second plate 536 from first working area 516 to plate receptacle 580 of second working area 518 to initiate the quantification processes in some implementations. Mover 572 may alternatively move second plate 536 from consumables area 514 to plate receptacle 580 of second working area 518 to initiate the quantification processes in implementations when second plate 536 remains in consumables area 514 during the transfer operations. Stage 570 aligns contact dispenser 568 with tip tray 524 of second working area 518 in some implementations and contact dispenser 558 couples with a tip 628 from tip tray 524.

[0087] Substrate 586 may be a plate having a well. Substrate 586 may be a consumable that is disposed of after use. Imaging system 588 may be spaced from substrate 586 andcoupled to a portion of system 500 such as a frame of system 500. Imaging system 588 may alternatively be carried by a stage.

[0088] Stage 570 aligns contact dispenser 568 with second plate 536 to perform the quantification processes and contact dispenser 568 aspirates a portion of second reagent 624 and sample 534 from well 538 of second plate 536. The portion of second reagent 624 and sample 534 may be about 2pL.

[0089] Stage 570 aligns contact dispenser 568 with substrate 586 and contact dispenser 568 dispenses the portion of second reagent 624 and sample 534 into a well of substrate 586 as an example. A dye may also be dispensed into the well of substrate 586 by contact dispenser 568. Imaging system 588 obtains image data of the portion of second reagent 624 and sample 534 within the well of substrate 586. Imaging system 588 and / or system 500 uses the image data to determine a concentration of sample 534. Mover 572 may move substrate 586 to waste 616 of consumables area 514 of second working area 518.

[0090] Substrate 586 may alternatively be implemented by a pair of plates 634, 636 between which a gap 638 is defined. Substrate 586 in such an implementation includes an inlet 640 and an outlet 642 in fluid communication with gap 638 and a seal 644 positioned between the pair of plates 634, 636. Plates 634, 636 and seal 644 define a channel 646 between inlet 640 and outlet 642. A waste reservoir 648 may be fluidly coupled to outlet 642 of substrate 586 by a fluidic line 650.

[0091] In the alternative implementation of substrate 586, stage 570 aligns contact dispenser 568 with inlet 640 of substrate 586 and contact dispenser 568 dispenses the portion of second reagent 624 and sample 534 into inlet 640 of substrate 586. The portion of second reagent 624 and sample 534 may flow and / or be positioned between inlet 640 and outlet 642 in this implementation and imaging system 588 obtains image data of the portion of second reagent 624 and sample 534. Imaging system 588 and / or system 500 uses the image data to determine a concentration of sample 534. Negative pressure, oil, and / or another substance may be used to urge the portion of second reagent 624 and sample 534 between inlet 640 and outlet 642. First plate 634 may alternatively be hingably coupled or removably coupled tosecond plate 636 to allow contact dispenser 568 to dispense the portion of second reagent 624 and sample 534 onto second plate 636 prior to first plate 634 being positioned overtop of second plate 636. System 500 may perform quantification processes in different ways, however.

[0092] System 500 may perform the normalization processes, according to one or more workflows, after the quantification processes are performed. Stage 570 aligns contact dispenser 568 to initiate the normalization processes in some implementations. Contact dispenser 568 aspirates a diluent 654 from a liquid reservoir 652 of second working area 518. Stage 570 then aligns contact dispenser 568 with second plate 536 and contact dispenser 568 dispenses diluent 654 into well 538 of second plate 536 to dilute sample 534 based on the concentration of the sample determined. Sample 534 within well 538 of second plate 536 will have a concentration within a threshold value after diluent 654 is added to well 538 as a result. Diluent 654 may be a buffer.

[0093] System 500 may perform the pooling processes, according to one or more workflows, after the quantification processes are performed. Stage 570 aligns contact dispenser 568 with tip tray 524 of second working area 518 and contact dispenser 568 places tip 628 in tip tray 524 and contact dispenser 568 then couples with another tip 630 from tip tray 524 to initiate the pooling processes in some implementations. Mover 572 moves a plate 610 from second working area 518 to plate receptacle 582 of second working area 518. Stage 570 aligns contact dispenser 568 with second plate 536 and contact dispenser 568 aspirates sample 534 from well 538 of second plate 536. Stage 570 then aligns contact dispenser 568 with third plate 610 and contact dispenser 568 dispenses sample 534 into well 606 of the third plate 610. Additional samples from other wells of second plate 536 may be deposited into well 606 of third plate 610 in a similar manner to combine a plurality of normalized samples together. A single tip can be used for the pooling processes. Contact dispenser 568 may pipette from final archive library well directly to pool and, thus, unique tips per sample may be used.

[0094] System 500 may perform the denaturing processes, according to one or more workflows, after the pooling processes are performed (though in some implementations, denaturing need not be performed). Stage 570 aligns contact dispenser 568 with tip tray 524 of second working area 518 and contact dispenser 568 places tip 630 in tip tray 524 and contact dispenser 568 then couples with another tip 632 from tip tray 524 to initiate the denaturing processes in some implementations. Contact dispenser 568 may use the same tip 630 used during the pooling processes in some implementations. Stage 570 aligns contact dispenser 568 with liquid reservoir 652 and contact dispenser 568 aspirates reagent 656 from liquid reservoir 652. Stage 570 then aligns contact dispenser 568 with third plate 610 and contact dispenser 568 dispenses reagent 656 into well 606 of third plate 610 to denature the pooled and normalized samples. Reagent 656 may be Sodium hydroxide (NaOH). Other denaturing processes may prove suitable. For example, Formamide or an equivalent may be used during the denaturing processes.

[0095] System 500 may dilute the pooled and denatured samples, according to one or more workflows, after the pooling and the denaturing processes are performed. Contact dispenser 568 aspirates diluent 654 from liquid reservoir 652 of second working area 518. Stage 570 then aligns contact dispenser 568 with third plate 610 and contact dispenser 568 dispenses diluent 654 into well 538 of third plate 610 to dilute sample 534 based on the concentration of the sample based on specifications of the sequencing system into which the sample is to be loaded. The pooled samples 534 within well 606 of third plate 610 will have a concentration within a threshold value after diluent 654 is added to well 606 as a result. Diluent 654 may be a buffer.

[0096] System 500 may perform the loading processes, according to one or more workflows, after the denaturing processes and / or after the diluting processes are performed. Mover 572 moves third plate 610 from second working area 518 to a plate receptacle 658 of loading area 520. Loading area 520 is shown including a stage 660 that can be used to move plate receptacle 658 relative to sipper manifold assembly 596. Sipper manifold assembly 596flows the denatured samples from well 538, 606 through the corresponding sipper(s) 598, through the fluidic line(s) 602, and out of system 500 to another system for sequencing.

[0097] System 500 also includes a drive assembly 662. Drive assembly 662 includes a pump drive assembly 664 and a valve drive assembly 666. Pump drive assembly 664 may be adapted to interface with pump 604 to pump fluid from reagent reservoir 594 to a noncontact dispenser. Valve drive assembly 666 may be adapted to interface with valve 600 to control the position of the valve 600.

[0098] In some aspects, more or fewer instances of the various components of the system 500 shown in FIG. 1 1 may be included in system 500 (e.g., four working areas , three consumable areas, etc.).

[0099] Example 1

[0100] An apparatus comprising: a plurality of assay bays, each assay bay of the plurality of assay bays comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber, the exhaust fans configured to draw air from the air drain chambers; a cabinet defining and enclosing a working chamber above the plurality of assay bays; and a cabinet fan positioned in the cabinet and having a filter, the cabinet fan configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure; wherein the cabinet fan and the exhaust fans in the plurality of assay bays create a first airflow that flows from the working chamber and through each of the air drain chambers.

[0101] Example 2

[0102] The apparatus of example 1 , wherein the plurality of assay bays are configured for asynchronous operation.

[0103] Example s

[0104] The apparatus of any one of examples 1 -2, comprising a baffle extending vertically between each of the plurality of assay bays.

[0105] Example 4

[0106] The apparatus of any one of examples 1 -3, wherein each exhaust fan comprises a filter.

[0107] Example s

[0108] The apparatus of any one of examples 1 -4, wherein: each of the plurality of assay bays comprises a thermocycler positioned on the deck; each deck comprises a first vent aperture extending through and transversely across a top surface of the deck and positioned along a proximate side of the thermocycler and a second vent aperture extending through and transversely across the top surface of the deck and positioned along a distal side of the thermocycler; and the first airflows pass from the working chamber to each of the air drain chambers through the first vent apertures and the second vent apertures.

[0109] Example s

[0110] The apparatus of any one of examples 1 -5, wherein each of the plurality of assay bays comprises: a movable drawer; a liquid waste receptacle mounted to the movable drawer; a third vent aperture extending through and transversely across a bottom of the drawer along a proximate side of the liquid waste receptacle; and a fourth vent aperture extending through and transversely across the bottom of the drawer along a distal side of the liquid waste receptacle; wherein the first airflows pass from the working chamber to each of the air drain chambers through the third vent apertures and the fourth vent apertures.

[0111] Example 7

[0112] The apparatus of example 6, wherein each of the plurality of assay bays comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the assay bay with the drawer in an open position.

[0113] Example s

[0114] The apparatus of example 7, wherein each of the drawer baffles are movable between a first position with the drawer in a closed position and a second position with the drawer in the open position.

[0115] Example s

[0116] The apparatus of any one of example 1 -8, comprising a consumables bay positioned adjacent a first side of the plurality of assay bays, wherein: the working chamber extends above the consumables bay; and a baffle extends vertically between the consumables bay and an adjacent assay bay.

[0117] Example 10

[0118] The apparatus of any one of examples 1 -9, wherein: the apparatus comprises a transfer bay positioned adjacent a second side of the plurality of assay bays; the working chamber extends above the transfer bay; the transfer bay comprises a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber of the transfer bay, the exhaust fan of the transfer bay configured to draw air from the air drain chamber of the transfer bay; and the cabinet fan and the exhaust fan in the transfer bay create a second airflow that flows from the working chamber and through the air drain chamber of the transfer bay.

[0119] Example 1 1

[0120] The apparatus of example 10, comprising a baffle extending vertically between the transfer bay and an adjacent assay bay.

[0121] Example 12

[0122] The apparatus of any one of examples 10-11 , wherein: the transfer bay comprises a quant station positioned on the deck; the deck comprises a fifth vent aperture extending through and transversely across a top surface of the deck and positioned along a proximate side of the quant station and a sixth vent aperture extending through and transversely across the top surface of the deck and positioned along a distal side of the quant station; and the second airflow passes from the working chamber to the air drain chamber of the transfer bay through the fifth vent aperture and the sixth vent aperture.

[0123] Example 13

[0124] The apparatus of any one of examples 10-12, wherein the transfer bay comprises: a movable drawer; a liquid waste receptacle mounted to the drawer; a seventh vent aperture extending through and transversely across a bottom of the drawer along a proximate side ofthe liquid waste receptacle; and an eighth vent aperture extending through and transversely across the bottom of the drawer along a distal side of the liquid waste receptacle; wherein the second airflow passes from the working chamber to the air drain chamber of the transfer bay through the seventh vent aperture and the eighth vent aperture.

[0125] Example 14

[0126] The apparatus of example 13, wherein the transfer bay comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the transfer bay with the drawer in an open position.

[0127] Example 15

[0128] The apparatus of example 14, wherein the drawer baffle is movable between a first position with the drawer in a closed position and a second position with the drawer in the open position.

[0129] Example 16

[0130] An apparatus, comprising: a plurality of assay bays, each assay bay of the plurality of assay bays comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber, the exhaust fans configured to draw air from the air drain chambers; a cabinet defining and enclosing a working chamber above the plurality of assay bays; and a cabinet fan positioned in the cabinet and having a filter, the cabinet fan configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure; wherein each of the plurality of assay bays comprises a movable drawer; a liquid waste receptacle mounted to the drawer; a third vent aperture extending through and transversely across a bottom of the drawer along a proximate side of the liquid waste receptacle; and a fourth vent aperture extending through and transversely across the bottom of the drawer along a distal side of the liquid waste receptacle; and the cabinet fan and the exhaust fans of the plurality of assay bays create first airflows that flow from the working chamber and to each of the air drain chambers through the third vent apertures and the fourth vent apertures.

[0131] Example 17

[0132] The apparatus of example 16, comprising a baffle extending vertically between each of the plurality of assay bays.

[0133] Example 18

[0134] The apparatus of any one of examples 16-17, wherein each of the plurality of assay bays comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the assay bay with the drawer in an open position.

[0135] Example 19

[0136] The apparatus of example 18, wherein each of the drawer baffles are movable between a first position with the drawer in a closed position and a second position with the drawer in the open position.

[0137] Example 20

[0138] An apparatus, comprising: a plurality of assay bays, each assay bay of the plurality of assay bays comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber, the exhaust fans of the assay bays configured to draw air from the air drain chambers of the assay bays; a transfer bay positioned adjacent a second side of the plurality of assay bays, the transfer bay comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber of the transfer bay, the exhaust fan of the transfer bay configured to draw air from the air drain chamber of the transfer bay; a cabinet defining and enclosing a working chamber above the plurality of assay bays and the transfer bay; and a cabinet fan positioned in the cabinet and having a filter, the cabinet fan configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure; wherein the cabinet fan, the exhaust fans of the assay bays, and the exhaust fan of the transfer bay create first airflows that flow from the working chamber and through each of the air drain chambers of the assay bays and a second airflow that flows from the working chamber and through the air drain chamber of the transfer bay.

[0139] Example 21

[0140] The apparatus of example 20, comprising a plurality of baffles extending vertically between each of the plurality of assay bays and extending vertically between the transfer bay and an adjacent assay bay.

[0141] Example 22

[0142] The apparatus of any one of examples 20-21 , wherein: the transfer bay comprises a quant station positioned on the deck; the deck comprises a fifth vent aperture extending through and transversely across a top surface of the deck and positioned along a proximate side of the quant station and a sixth vent aperture extending through and transversely across the top surface of the deck and positioned along a distal side of the quant station; and the second airflow passes from the working chamber to the air drain chamber of the transfer bay through the fifth vent aperture and the sixth vent aperture.

[0143] Example 23

[0144] The apparatus of any one of examples 20-22, wherein the transfer bay comprises: a movable drawer; a liquid waste receptacle mounted to the drawer; a seventh vent aperture extending through and transversely across a bottom of the drawer along a proximate side of the liquid waste receptacle; and an eighth vent aperture extending through and transversely across the bottom of the drawer along a distal side of the liquid waste receptacle; wherein the second airflow passes from the working chamber to the air drain chamber of the transfer bay through the seventh vent aperture and the eighth vent aperture.

[0145] Example 24

[0146] The apparatus of example 23, wherein the transfer bay comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the transfer bay with the drawer in an open position.

[0147] Example 25

[0148] The apparatus of example 24, wherein the drawer baffle is movable between a first position with the drawer in a closed position and a second position with the drawer in the open position.

[0149] 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.

[0150] 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.

[0151] The terms “connect,” “connected,” “contact” “coupled” and / or the like are broadly defined herein to encompass a variety of divergent arrangements and assembly techniques. These arrangements and techniques include, but are not limited to (1 ) the direct joining of one component and another component with no intervening components therebetween ( / .e., the components are in direct physical contact); and (2) the joining of one component and another component with one or more components therebetween, provided that the one component being “connected to” or “contacting” or “coupled to” the other component is somehow in operative communication (e.g., electrically, fluidly, physically, optically, etc.) with the other component (notwithstanding the presence of one or more additional components therebetween). It is to be understood that some components that are in direct physical contact with one another may or may not be in electrical contact and / or fluid contact with one another. Moreover, two components that are electrically connected, electrically coupled, optically connected, optically coupled, fluidly connected or fluidly coupled may or may not be in direct physical contact, and one or more other components may be positioned therebetween.

[0152] The terms “generally”, “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%.

[0153] 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.

[0154] 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.

[0155] 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. Inparticular, 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 apparatus, comprising: a plurality of assay bays, each assay bay of the plurality of assay bays comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber, the exhaust fans configured to draw air from the air drain chambers; a cabinet defining and enclosing a working chamber above the plurality of assay bays; and a cabinet fan positioned in the cabinet and having a filter, the cabinet fan configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure; wherein the cabinet fan and the exhaust fans in the plurality of assay bays create a first airflow that flows from the working chamber and through each of the air drain chambers.

2. The apparatus of claim 1 , wherein the plurality of assay bays are configured for asynchronous operation.

3. The apparatus of any one of the preceding claims, comprising a baffle extending vertically between each of the plurality of assay bays.

4. The apparatus of any one of the preceding claims, wherein each exhaust fan comprises a filter.

5. The apparatus of any one of the preceding claims, wherein: each of the plurality of assay bays comprises a thermocycler positioned on the deck; each deck comprises a first vent aperture extending through and transversely across a top surface of the deck and positioned along a proximate side of the thermocycler and a second vent aperture extending through and transversely across the top surface of the deck and positioned along a distal side of the thermocycler; and the first airflows pass from the working chamber to each of the air drain chambers through the first vent apertures and the second vent apertures.

6. The apparatus of any one of the preceding claims, wherein each of the plurality of assay bays comprises: a movable drawer; a liquid waste receptacle mounted to the movable drawer; a third vent aperture extending through and transversely across a bottom of the movable drawer along a proximate side of the liquid waste receptacle; and a fourth vent aperture extending through and transversely across the bottom of the movable drawer along a distal side of the liquid waste receptacle; wherein the first airflows pass from the working chamber to each of the air drain chambers through the third vent apertures and the fourth vent apertures.

7. The apparatus of claim 6, wherein each of the plurality of assay bays comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the assay bay with the movable drawer in an open position.

8. The apparatus of claim 7, wherein each of the drawer baffles are movable between a first position with the movable drawer in a closed position and a second position with the movable drawer in the open position.

9. The apparatus of any one of the preceding claims, comprising a consumables bay positioned adjacent a first side of the plurality of assay bays, wherein: the working chamber extends above the consumables bay; and a baffle extends vertically between the consumables bay and an adjacent assay bay.

10. The apparatus of any one of the preceding claims, wherein: the apparatus comprises a transfer bay positioned adjacent a second side of the plurality of assay bays; the working chamber extends above the transfer bay; the transfer bay comprises a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber of the transfer bay, the exhaust fan of the transfer bay configured to draw air from the air drain chamber of the transfer bay; and the cabinet fan and the exhaust fan in the transfer bay create a second airflow that flows from the working chamber and through the air drain chamber of the transfer bay.11 . The apparatus of claim 10, comprising a baffle extending vertically between the transfer bay and an adjacent assay bay.

12. The apparatus of claim 10, wherein: the transfer bay comprises a quant station positioned on the deck; the deck comprises a fifth vent aperture extending through and transversely across a top surface of the deck and positioned along a proximate side of the quant station and a sixth vent aperture extending through and transversely across the top surface of the deck and positioned along a distal side of the quant station; andthe second airflow passes from the working chamber to the air drain chamber of the transfer bay through the fifth vent aperture and the sixth vent aperture.

13. The apparatus of claim 10, wherein the transfer bay comprises: a movable drawer; a liquid waste receptacle mounted to the movable drawer; a seventh vent aperture extending through and transversely across a bottom of the movable drawer along a proximate side of the liquid waste receptacle; and an eighth vent aperture extending through and transversely across the bottom of the movable drawer along a distal side of the liquid waste receptacle; wherein the second airflow passes from the working chamber to the air drain chamber of the transfer bay through the seventh vent aperture and the eighth vent aperture.

14. The apparatus of claim 13, wherein the transfer bay comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the transfer bay with the movable drawer in an open position.

15. The apparatus of claim 14, wherein the drawer baffle is movable between a first position with the movable drawer in a closed position and a second position with the movable drawer in the open position.

16. An apparatus, comprising: a plurality of assay bays, each assay bay of the plurality of assay bays comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber, the exhaust fans configured to draw air from the air drain chambers; a cabinet defining and enclosing a working chamber above the plurality of assay bays; and a cabinet fan positioned in the cabinet and having a filter, the cabinet fan configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure; wherein each of the plurality of assay bays comprises a movable drawer; a liquid waste receptacle mounted to the movable drawer; a third vent aperture extending through and transversely across a bottom of the movable drawer along a proximate side of the liquid waste receptacle; and a fourth vent aperture extending through and transversely across the bottom of the movable drawer along a distal side of the liquid waste receptacle; and the cabinet fan and the exhaust fans of the plurality of assay bays create first airflows that flow from the working chamber and to each of the air drain chambers through the third vent apertures and the fourth vent apertures.

17. The apparatus of claim 16, comprising a baffle extending vertically between each of the plurality of assay bays.

18. The apparatus of any one of claims 16-17, wherein each of the plurality of assay bays comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the assay bay with the movable drawer in an open position.

19. The apparatus of claim 18, wherein each of the drawer baffles are movable between a first position with the movable drawer in a closed position and a second position with the movable drawer in the open position.

20. An apparatus, comprising: a plurality of assay bays, each assay bay of the plurality of assay bays comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber, the exhaust fans of the assay bays configured to draw air from the air drain chambers of the assay bays; a transfer bay positioned adjacent a second side of the plurality of assay bays, the transfer bay comprising a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber of the transfer bay, the exhaust fan of the transfer bay configured to draw air from the air drain chamber of the transfer bay; a cabinet defining and enclosing a working chamber above the plurality of assay bays and the transfer bay; and a cabinet fan positioned in the cabinet and having a filter, the cabinet fan configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure; wherein the cabinet fan, the exhaust fans of the assay bays, and the exhaust fan of the transfer bay create first airflows that flow from the working chamber and through each of the air drain chambers of the assay bays and a second airflow that flows from the working chamber and through the air drain chamber of the transfer bay.21 . The apparatus of claim 20, comprising a plurality of baffles extending vertically between each of the plurality of assay bays and extending vertically between the transfer bay and an adjacent assay bay.

22. The apparatus of any one of claims 20-21 , wherein: the transfer bay comprises a quant station positioned on the deck; the deck comprises a fifth vent aperture extending through and transversely across a top surface of the deck and positioned along a proximate side of the quant station and a sixth vent aperture extending through and transversely across the top surface of the deck and positioned along a distal side of the quant station; and the second airflow passes from the working chamber to the air drain chamber of the transfer bay through the fifth vent aperture and the sixth vent aperture.

23. The apparatus of any one of claims 20-22, wherein the transfer bay comprises: a movable drawer; a liquid waste receptacle mounted to the movable drawer; a seventh vent aperture extending through and transversely across a bottom of the movable drawer along a proximate side of the liquid waste receptacle; and an eighth vent aperture extending through and transversely across the bottom of the movable drawer along a distal side of the liquid waste receptacle; wherein the second airflow passes from the working chamber to the air drain chamber of the transfer bay through the seventh vent aperture and the eighth vent aperture.

24. The apparatus of claim 23, wherein the transfer bay comprises a drawer baffle configured to substantially limit external airflow into the air drain chamber of the transfer bay with the movable drawer in an open position.

25. The apparatus of claim 24, wherein the drawer baffle is movable between a first position with the movable drawer in a closed position and a second position with the movable drawer in the open position.

26. An apparatus, comprising:a deck defining an air drain chamber and an exhaust fan in fluid communication with the air drain chamber, the exhaust fan configured to draw air from the air drain chamber; a cabinet defining and enclosing a working chamber above the deck; and a cabinet fan positioned in the cabinet and having a filter, the cabinet fan configured to deliver air into the working chamber to keep the working chamber at a positive pressure above atmospheric pressure; wherein the cabinet fan and the exhaust fan create a first airflow that flows from the working chamber and through the air drain chambers.

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