Substrate orientation device for liquid dispensing operations

Abstract

The substrate orientation device comprises a frame that supports a substrate onto which a liquid is dispensed, for example as may be relevant in the manufacture of (bio)chemical microarrays. The frame is movable to different positions, for example to attach the substrate to the frame, to dispense droplets onto the substrate, and to apply bulk liquid to the substrate. The substrate orientation device may also be movable to different locations for different liquid dispensing devices, such as printers and flow cells.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. §§ 120, 363, and 365(c) of U.S. patent application Ser. No. 18 / 105,110, filed Feb. 2, 2023, entitled "SUBSTRATE ORIENTATION DEVICE FOR LIQUID DISPENSING OPERATIONS," the entire contents of which are incorporated herein by reference.

[0002] The present invention relates generally to liquid dispensing operations, such as may be part of the manufacture of microarrays, e.g., nucleic acid microarrays, which may include droplet deposition onto a substrate and separate application of bulk liquid to the substrate. In particular, the present invention relates to devices that orient or reorient a substrate to a different position as part of one or more liquid dispensing operations. [Background technology]

[0003] Liquid dispensing operations, such as microarray fabrication, can involve using a liquid dispensing device, such as a printer (e.g., an inkjet printer), to deposit droplets at selected sites on a substrate, such as a glass slide, to form (or add material to) an array of spots (typically two-dimensional) on the substrate. Depending on the application, these spots can be sites for performing chemical or biochemical reactions or synthesis (e.g., nucleotides, proteins, etc.) and / or analysis of one or more components or characteristics of the spots. One example of microarray fabrication is depositing droplets of nucleoside phosphoramidites in a solvent onto a substrate as part of the synthesis of a biomolecule (e.g., nucleic acid). The substrate surface with the spots can then be post-processed in a flow cell module separate from the printer. In this flow cell module, one or more bulk fluids are flowed over the substrate surface as needed to prepare the substrate surface for the next printing iteration (e.g., to extend oligonucleotides on the substrate surface). In other words, after processing in the flow cell module, the substrate may be returned to the printer, whereupon additional droplets may be deposited onto existing spots where other droplets had previously been dispensed. The separate steps of printing and flow cell processing may be repeated any number of times depending on the application.

[0004] In known microarray fabrication systems, substrates are mounted horizontally on a substrate holder and then on an XY stage. A horizontal orientation is optimal for printing because it promotes accuracy, precision, uniformity, and reproducibility in the process of printing droplets at pre-specified addresses on the substrate surface. The XY stage then moves the substrate under the jets of an inkjet printer. Once printing is complete, the XY stage moves the substrate to a swap station, where a robotic arm equipped with a substrate gripper is located. The robotic arm then picks up the substrate from the substrate holder and transfers it to a different substrate holder in a flow cell module. In the flow cell module, the substrate is held in a vertical position with the spot facing the interior space of the flow cell. A vertical orientation is optimal for fluid movement within the flow cell, such as achieving uniform liquid flow and facilitating the removal of air bubbles from the liquid within the flow cell.

[0005] Known systems are disadvantageous for several reasons. Known systems require the use of complex and precise robotic arms and swap stations to perform substrate transfer to the flow cell module. The robotic arms can accidentally drop and damage substrates. Furthermore, known systems require the use of two or more substrate holders and complex camera / machine vision hardware to ensure precise and accurate reorientation and realignment of the substrate in horizontal and vertical positions. In known systems, substrates must be precisely and precisely realigned each time they are removed and repositioned between each print and flow cell processing cycle. As a result of the multiple steps required to manipulate the substrate (moving / removing, positioning / repositioning, aligning / realigning), manipulation errors can accumulate.

[0006] Thus, there is a continuing need for further developments in devices, systems and methods related to liquid dispensing operations such as may be part of microarray manufacturing. Summary of the Invention

[0007] To address the above needs, in whole or in part, as well as other needs that may be recognized by those skilled in the art, the present disclosure provides methods, processes, systems, apparatus, instruments, and / or devices, as described by way of example in the embodiments set forth below.

[0008] According to an embodiment, a substrate orientation device for orienting a substrate configured as a solid support for liquid dispensing comprises a base and a frame configured to support the substrate and move to a first position and a second position relative to the base, wherein in the first position the frame is substantially parallel to the base and in the second position the frame is oriented at an angle relative to the base.

[0009] According to another embodiment, a liquid dispensing system comprises a substrate orientation device according to any of the embodiments disclosed herein and a liquid dispensing device configured to dispense liquid onto the substrate while the substrate is supported by the frame.

[0010] According to another embodiment, a method for dispensing a liquid onto a substrate includes providing a substrate orientation device according to any of the embodiments disclosed herein, mounting a substrate on a frame of the substrate orientation device, moving the frame to a first position, moving the frame to a second position, and dispensing a liquid onto the substrate before or after moving the frame to the first position and the second position.

[0011] According to another embodiment, a method for dispensing a liquid onto a substrate includes providing a substrate orienting device having a base and a frame configured to support a substrate, mounting the substrate to the frame, moving the frame relative to the base to a first position in which the frame is substantially parallel to the base, moving the frame relative to the base to a second position in which the frame is oriented at an angle to the base, and dispensing the liquid onto the substrate before or after moving the frame to the first and second positions.

[0012] According to another embodiment, a non-transitory computer-readable medium has stored thereon instructions that, when executed on a processor, control or perform one or more of the steps of any of the methods disclosed herein.

[0013] According to another embodiment, a fluid dispensing system includes a non-transitory computer-readable storage medium.

[0014] Other devices, apparatus, systems, methods, features, and advantages of the present invention will be or become apparent to one with skill in the art upon examination of the following figures and detailed description, and it is intended that all such additional systems, methods, features, and advantages be included within this specification, be within the scope of the present invention, and be protected by the accompanying claims.

[0015] The present invention can be better understood by referring to the following drawings, in which components are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention, in which like reference characters designate corresponding parts throughout the different drawings. [Brief explanation of the drawings]

[0016] [Figure 1] FIG. 1 is a top view of an example microarray according to an embodiment of the present disclosure. [Figure 2A] 1 is a perspective view of an example of a substrate orientation device according to an embodiment of the present disclosure, showing the substrate orientation device in a first position. [Figure 2B] 2B is a perspective view of the substrate orienting device shown in FIG. 2A rotated approximately 180 degrees relative to FIG. 2A, showing the substrate orienting device oriented in a second position. [Figure 2C] 2B is a side view of the substrate orienting device shown in FIG. 2A, showing the substrate orienting device oriented in a further position different from the first and second positions, according to an embodiment of the present disclosure. [Figure 3] 2B is a side view of a substrate orientation device oriented in a first position shown in FIG. 2A and positioned at a print station according to an embodiment of the present disclosure. [Figure 4A] FIG. 1 is a side view of a substrate orienting device oriented in an open flow cell position and positioned in a flow cell station, according to an embodiment of the present disclosure. [Figure 4B] FIG. 1 is a side view of a substrate orienting device oriented in a closed flow cell position and positioned in a flow cell station, according to an embodiment of the present disclosure. [Figure 5A] 1 is a perspective view of an example liquid dispensing system showing a substrate orientation device oriented in a first position and positioned in a printer, according to an embodiment of the present disclosure. [Figure 5B] 5B is a perspective view of the liquid dispensing system shown in FIG. 5A showing the substrate orienting device oriented in a first position and positioned in a flow cell assembly according to an embodiment of the present disclosure. [Figure 5C] FIG. 5B is a perspective view of the liquid dispensing system shown in FIG. 5A showing the substrate orienting device oriented in a second position and positioned in a flow cell assembly according to an embodiment of the present disclosure. [Figure 6] FIG. 10 is a front view of another example of a liquid dispensing system according to an embodiment of the present disclosure. [Figure 7] FIG. 1 is a schematic diagram of a system controller for a liquid dispensing system according to an embodiment of the present disclosure. [Figure 8] 1 is a flow chart illustrating an example of a method for dispensing a liquid, according to an embodiment of the present disclosure. [Figure 9] 10 is a flow chart illustrating another example of a method for dispensing a liquid, according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0017] All representations in the drawings are to be considered schematic unless expressly stated otherwise.

[0018] In this disclosure, all described "embodiments," "aspects," "examples," and "embodiments" are considered to be non-limiting and non-exclusive. Thus, the fact that a particular "embodiment," "aspect," "example," or "embodiment" is explicitly described herein does not exclude other "embodiments," "aspects," "examples," and "embodiments" from the scope of the disclosure, even if they are not explicitly described. In this disclosure, the terms "embodiment," "aspect," "example," and "embodiment" are used interchangeably, i.e., are considered to have interchangeable meanings.

[0019] In this disclosure, the terms "substantially," "approximately," or "about," when modifying a particular numerical value, can be interpreted as encompassing a range of values ​​including ±10% of that numerical value, unless otherwise specified.

[0020] In this disclosure, the term "liquid" includes a single liquid-phase composition or a mixture or blend of two or more liquid-phase compositions. Examples of liquids include, but are not limited to, a solution, a suspension, a colloid, or an emulsion. A liquid can contain or carry solid particles (e.g., inorganic particles, intact biological cells or dissolved cellular components, etc.) and / or gas or vapor bubbles.

[0021] In this disclosure, the term "(bio)chemical compound" encompasses chemical compounds and biological compounds (or biomolecules). Chemical compounds can be, for example, small or large molecular weight molecules (e.g., polymers, etc.). Biological compounds can be, for example, biopolymers. Examples include, but are not limited to, nucleic acids (or polynucleotides), such as deoxyribonucleotides, ribonucleotides, oligonucleotides (or "oligos"), proteins, carbohydrates, sugars, lipids, and analogs or derivatives thereof.

[0022] In this disclosure, the term "interaction" generally refers to an interaction between two or more components, where the components involved in the interaction may be one or more elements, one or more molecules, or a combination of one or more elements and one or more molecules. The term "interaction" encompasses (bio)chemical reactions, including (bio)chemical synthesis.

[0023] FIG. 1 is a top view of an example of an array (or microarray) 100 that can be fabricated by the devices, systems, and methods described herein. The microarray 100 can be configured for a variety of applications, such as in fields such as immunoassays, genomics, proteomics, metabolomics, cellular analysis, disease diagnostics or other disease analysis or prediction, drug discovery, and combinatorial chemistry. Alternatively, molecules synthesized as the microarray 100 can be cleaved or removed, in whole or in part, from the substrate 104 and used for a variety of applications in the fields listed above. The microarray 100 includes a solid substrate 104 and a one-dimensional (1D) or (more generally) two-dimensional (2D) array of spots 108 (or features, liquid dispensing sites, "virtual wells," physical depressions, ridges, etc.) disposed on a top surface (or substrate surface) 112 of the substrate 104. The spots 108 can correspond to discrete, individually identifiable locations on the top surface 112. Furthermore, the spots 108 are individually addressable (eg, assignable to individual (XY) coordinates) and identifiable and locatable by appropriate equipment such as a camera or other type of sensor.

[0024] The substrate 104 is configured as a solid support for liquid dispensing operations that may be part of microarray fabrication, as described above. That is, the substrate 104 (or at least its upper surface 112, or at least the areas in contact with the spots 108) can be composed of any solid material suitable for serving as a solid support for (bio)chemical interactions to be performed at the sites of the spots 108, depending on the application. As one example, the (bio)chemical reactions may be part of the synthesis of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Examples of materials for the substrate 104 include, but are not limited to, various glasses, quartz or fused silica, polymer-coated glass, polymers (e.g., poly(methyl methacrylate) or PMMA, polydimethylsiloxane or PDMS, epoxy-based polymers such as SU-8, etc.), ceramics, and silicon. The upper surface 112 of the substrate 104 (or at least the areas in contact with the spots 108) can be derivatized / functionalized / modified as needed for a particular application, as will be understood by those skilled in the art. For example, the substrate 104 can be pretreated to render the top surface 112 (or at least the areas that will contact the spots 108) hydrophobic, thereby optimizing the formation of uniform or homogeneous spots 108. For example, after a dispensed droplet contacts a designated spot 108 on the top surface 112, the droplet can be uniform in size and maintain a substantially hemispherical or dome-like shape. Silanized glass is one example of a pretreated substrate 104. As another example, the substrate 104 can be pretreated in the sense that the spots 108 are initially formed with starting materials (e.g., biochemical probes, pads configured to promote oligonucleotide extension, etc.) prior to performing any of the liquid dispensing methods disclosed herein.

[0025] Substrate 104 is typically (although not necessarily) flat or plate-like, meaning that the thickness of substrate 104 (into the plane of the drawing) is its smallest physical dimension compared to the length and width of substrate 104 in the horizontal plane as shown in Figure 1. Thus, in various embodiments, the substrate may be characterized as a plate, slide, chip, etc. Substrate 104 is typically (although not necessarily) rectilinear in shape, as shown in Figure 1.

[0026] In this example, the top surface 112 of the substrate 104 is a flat, continuous surface, and the spots 108 each define (or are located in) a virtual well, rather than an actual, structurally distinct well formed in the substrate 104. However, in other embodiments, the substrate 104 may include recesses or actual wells (such as in a microplate) to serve as individually addressable sites for receiving dispensed droplets. In other words, the spots 108 may be located within actual wells of the substrate 104. Alternatively, the spots 108 may be defined on (or located in) respective raised features that serve as individually addressable sites for receiving dispensed droplets.

[0027] The composition of the spot 108 depends on the application being performed and the current stage or step of the application being performed. For example, before performing a certain step of droplet deposition on the spot 108, the spot 108 may be an "empty" position on the upper surface 112, i.e., a position that does not contain any material. As another example, before performing a certain step of droplet deposition on the spot 108, the spot 108 may contain functional groups and / or one or more partially or completely dried materials. After performing a certain step of droplet deposition on the spot 108 (or a selected subset of the spots 108 of the entire array of spots 108), the spot 108 contains a droplet (i.e., material that is part of the dispensed droplet). At a certain point in time, the droplet material on the spot 108 may be partially or completely dried, depending on the degree of evaporation that has occurred. At a certain point in time, the spot 108 may contain the product of one or more (bio)chemical interactions performed during the microarray fabrication process. For example, in the case of DNA or RNA microarray fabrication, the spots 108 can be or include DNA or RNA probes immobilized on the upper surface 112 of the substrate 104 (or at least the sites of the spots 108 on the upper surface 112) and target molecules bound to the DNA or RNA probes. Protein-based arrays can also be fabricated by application of the subject matter disclosed herein, such as for analyzing protein-protein or protein-ligand interactions. As another example, the spots 108 can be or include the result of non-biological chemical reactions, synthesis, or other types of interactions between non-biological chemical compounds. More generally, the composition of the spots 108 can vary during the liquid dispensing or array fabrication process. For example, the composition of the spots 108 can be different at different locations during different intermediate stages of the array fabrication process. Depending on the stage of the array fabrication process, the spots 108 may be dry or non-dry when a particular liquid dispensing step is performed.

[0028] The number of rows and columns of spots 108, as well as the total number of spots 108, shown in Figure 1 are merely exemplary. By way of example, the number of spots 108 can range from a few (e.g., 10) to 100 or hundreds (e.g., for diagnostic applications), to hundreds of thousands or millions (e.g., for high-throughput research or screening applications). The spacing between adjacent spots 108 is typically uniform across the array, but this is not a requirement. The spacing between adjacent spots 108 is typically large enough to avoid cross-contamination or merging between adjacent spots 108 and to allow the spots 108 to be spatially distinct and individually distinguishable (e.g., individually addressable by detection / imaging techniques). For example, the volume of the droplets deposited on the substrate 104 can be on the order of picoliters (pL) (e.g., in the range of 1 or a few pL to 1000 pL) or on the order of nanoliters (nL) (e.g., in the range of 1 or a few nL to 1000 nL), the diameter of the spots 108 on the substrate 104 after receiving the droplets and the spacing between adjacent spots 108 can be on the order of micrometers (μl) (e.g., in the range of 1 or a few μm to 1000 μm), and the density of the spots 108 in the microarray 100 can be on the order of spots per square centimeter (cm 2 ) can be on the order of thousands, tens of thousands, or hundreds of thousands per surface 112. The constructed microarray 100 can be used as a means to produce individual molecules or libraries of molecules, which can then be used as microarrays or detached in whole or in part from the surface 112.

[0029] Examples of microarray fabrication are described, for example, in U.S. Patent Application Publication No. 2008 / 0206850, U.S. Patent No. 8,778,849, "POSaM: a fast, flexible, open-source, inkjet oligonucleotide synthesizer and microarrayer" by Lausted et al., Genome Biology, Vol. 5, Issue 8, Article R58 (2004), "Fabrication of high quality microarrays" by Dufva, Biomolecular Engineering (2005), and "Bio-Microarray Fabrication—A Review" by Barbulovic-Nad et al., Critical Reviews in Biotechnology, 26:237-259 (2006), the entire contents of each of which are incorporated herein by reference.

[0030] 2A-2C illustrate an example of a substrate orientation device 200 according to an embodiment of the present disclosure. In particular, FIG. 2A is a perspective view of the substrate orientation device 200 while in a first position, FIG. 2B is a perspective view of the substrate orientation device 200 while in a second position different from the first position, and FIG. 2C is a side view of the substrate orientation device while in a further position different from the first and second positions. For purposes of illustration, FIG. 2A (and several other figures) includes an arbitrarily positioned Cartesian coordinate system (XYZ) reference system. The X and Y axes are considered to lie in a horizontal (XY) plane, which may correspond to any ground area or other surface (e.g., a workbench, table, floor, equipment deck, etc.) on which the substrate orientation device 200 rests, is mounted, or is otherwise supported. Accordingly, the Z axis is considered to correspond to the vertical direction. The X, Y, and Z dimensions (such as may be associated with the substrate orientation device 200 or any of its components) are considered to be length, width, and height, respectively. The perspective of FIG. 2B is rotated approximately 180 degrees about the Z axis relative to FIG. 2A.

[0031] In the illustrated example, the substrate orientation device 200 includes a base 216 and a frame 220 configured to support one or more substrates 104 (two substrates 104 in the illustrated example). The base 216 and the frame 220 may generally be planar structural members (e.g., plates) constructed from any suitable rigid material (e.g., various metals, metal alloys, hard plastics, etc.). The base 216 may serve as the main structural support for the remainder of the substrate orientation device 200. In one embodiment, the base 216 is also configured to be mounted to a movable stage, as described below. In the illustrated example, the substrate orientation device 200 also includes one or more substrate holders 228, which may be attached to or be an integral part of the frame 220. For example, the frame 220 and the substrate holder 228 may include mounting mechanisms (not shown; e.g., mounting / alignment pins and corresponding mounting / alignment holes, clamps, other types of fastening components, etc.) configured to engage with one another to enable the substrate holder 228 to be securely fastened to the frame 220. Thus, the substrate holder 228 may be removably mounted to the frame 220. Alternatively, the substrate holder 228 may be permanently attached to or integral with the frame 220. In the latter case, the frame 220 and the substrate holder 228 may be considered the same component. In either case, the substrate 104 is considered to be supportable by or mountable to the frame 220, either directly or indirectly (through the use of a separate substrate holder 228).

[0032] The frame 220, or each substrate holder 228, if provided, is configured to hold the substrate 104 in a secure and reproducible position on the upper surface of the frame 220 or substrate holder 228. To this end, the frame 220 or substrate holder 228 may be equipped with a suitable mechanical mounting mechanism (e.g., clamps, pins, adhesive, etc.). Alternatively or additionally, the frame 220 or substrate holder 228 may be or include a vacuum chuck configured to hold the substrate 104 by application of a vacuum at the underside of the substrate 104. In the latter case, the frame 220 or substrate holder 228 may be in communication with a suitable vacuum source, such as any suitable type of vacuum pump (not shown).

[0033] The frame 220 (and thus the substrate 104 when supported on the frame 220, and, if present, a separate substrate holder 228) is also configured to move between (or to) various positions relative to the base 216. For example, FIG. 2A shows the frame 220 in a first position parallel or substantially parallel to the base 216, while FIG. 2B shows the frame 220 in a second position oriented at an angle relative to the base 216. Considering that the base 216 is oriented in the XY plane at zero degrees relative to a plane partially defined by the Z axis, the term "substantially parallel" can be considered to mean that in the first position, the frame 220 is oriented at zero degrees ±10 degrees. In the illustrated example, in the second position, the frame 220 is positioned substantially perpendicular to the base 216, i.e., in the XZ plane, at an angle of 90 degrees relative to the XY plane. The term "substantially vertical" can be considered to mean that in the second position, the frame 220 is oriented 90 degrees ±10 degrees relative to the first position, or base 216, or the XY plane. Thus, in this example, the first position is a horizontal position and the second position is a vertical position. As noted above in the Background section, a horizontal orientation is optimal for printing (or other types of droplet deposition), while a vertical orientation is optimal for bulk fluid movement in a flow cell.

[0034] In this embodiment, the frame 220 is configured to move to and between various positions, including a first position shown in FIG. 2A and a second position shown in FIG. 2B. The frame 220 can also be configured to move between the first and second positions. The frame 220 can also be configured to move to additional positions. Depending on the movement sequence required for a certain application, one or more "additional" positions may be intermediate positions relative to the first and second positions shown. For example, the additional intermediate positions may be oriented at an angle relative to the first and second positions. One such additional or intermediate position is shown in FIG. 2C. Generally, movement to and between various positions can involve rotation about one or more axes, linear translation along one or more axes, or a combination of both. In the illustrated example, the substrate orienting device 200 is configured as a hinge, which allows the frame 220 (and any components supported by the frame 220, such as the illustrated substrate 104 and substrate holder 228) to rotate to or between one or more positions relative to the base 216. In the illustrated example, the substrate orientation device 200 is configured to "flip" the frame 220 from a first position to a second position, and alternately from the second position to the first position. Examples of positions available in addition to the first position shown in FIG. 2A and the second position shown in FIG. 2B are described with reference to FIG. 2C and FIGS. 4A-6. Furthermore, as indicated by the arrows in FIG. 2B and as described in more detail below, the substrate orientation device 200 (e.g., as a whole) may be movable along one or more (usually horizontal) axes, such as the X-axis or both the X-axis and the Y-axis.

[0035] In various embodiments, the first position shown in Figure 2A can be considered a liquid dispensing position, where liquid is dispensed onto substrate 104, as described below in connection with Figure 3. The first position can also be considered a substrate mounting position, where substrate 104 is mounted to frame 220 (or directly to substrate holder 228, if provided). Alternatively, an additional position oriented at an angle relative to the first position can be utilized as a substrate mounting position, as shown in Figure 2C. The second position shown in Figure 2B can be considered an open-cell position or a closed-cell position, and the closed-cell position can be considered a liquid dispensing position, as described below in connection with Figures 4A and 4B.

[0036] In general, the substrate orientation device 200 can have any suitable configuration to allow the frame 220 to move relative to the base 216. In one embodiment illustrated in FIGS. 2A and 2B , the substrate orientation device 200 includes a coupling device 222 configured to couple the frame 220 to the base 216. In the illustrated example, the coupling device 222 includes a shaft (or pin, rod, etc.) 224 rotatably mounted by one or more shaft supports 236. The shaft 224 has at least one degree of freedom, namely, rotational freedom about its rotational axis (or pivot axis) A, which in this example corresponds to (or is parallel to) the X-axis. In this example, the frame 220 and the shaft 224 are rotatable together relative to the (fixed) base 216 about the rotational axis A, as indicated by the curved arrow in FIG. 2A . The shaft supports 236 may be attached to or integral with the frame 220 and / or the base 216. In the illustrated example, axle 224 extends into or through a bore in each axle support 236. In the illustrated example, at least a portion of frame 220 is located at pivot axis A and is disposed between the two axle supports. Axle supports 236 may be or include any suitable type of bearing (e.g., plain bearing, ball bearing, roller bearing, air bearing, magnetic bearing, etc.), as will be understood by those skilled in the art.

[0037] In another embodiment (not shown), the shaft 224 can be divided into two or more shaft segments, with each shaft segment supported by a corresponding shaft support. In another embodiment, the shaft 224 can be fixed (non-rotatable), and the shaft supports 236 can be attached to or integral with the frame 220 and rotatable about the shaft 224. More generally, the shaft 224 and shaft supports 236 can be positioned anywhere on or within the substrate orientation device 200 to effectively allow the frame 220 (and any components supported thereby, such as the illustrated substrate 104 and substrate holder 228) to be rotatable relative to the base 216.

[0038] 2A and 2B, the substrate orienting device 200 further comprises an actuator 232. In one embodiment, in addition to the coupling frame 220 and the base 216, the coupling device 222 can be configured to couple the actuator 232 and the frame 220 and / or the base 216. Alternatively, a separate coupling device (not shown) may be provided to couple the actuator 232 and the frame 220 and / or the base 216. Generally, the actuator 232 can have any configuration suitable for driving movement of the frame 220 via the coupling device 222 in this example. In this example, the actuator 232 includes a suitable motor 240 (e.g., an electric stepper motor or servo motor) mechanically coupled to the shaft 224 (or, alternatively, to the shaft support 236 if the shaft 224 is movable and the shaft support 236 is fixed). The actuator 232 can include any suitable mechanical linkage or linkage assembly necessary to transmit the driving force generated by the motor 240 to the frame 220. This power transmission may involve one or more transformations of one type of motion (e.g., rotation, linear translation, etc.) to another type of motion, as will be understood by those skilled in the art. Depending on the implementation, shaft 224 and / or shaft support 236 may be considered part of a mechanical linkage. This mechanical linkage may include other types of components, such as rotary and / or linear guides, rotary and / or linear bearings, toothed components, cams and cam followers, etc., as will be understood by those skilled in the art.

[0039] As an alternative to an electric motor, the motor 240 can be a pneumatic or hydraulic device, as will be understood by those skilled in the art. As another alternative, movement of the frame 220 may be performed by manual operation. For example, the actuator 232 may include a handle or lever (not shown) that is operable by a user of the substrate orientation device 200. A user-operated handle may be applied to the motor 240. For example, the substrate orientation device 200 may be configured to allow a user to disengage the electric operation of the motor 240, thereby using the handle instead to drive movement of the frame 220.

[0040] FIG. 3 is a side view of substrate orienting device 200 in a first position (i.e., frame 220, along with any components supported by frame 220, if present, e.g., substrate 104 and substrate holder 228, are positioned in the first position as shown in FIG. 2A ) and positioned at a liquid dispensing station, according to an embodiment of the present disclosure. A liquid dispensing device 334 is positioned at the liquid dispensing station. In this example, the liquid dispensing station is a printer station, and liquid dispensing device 334 is a printer (module or assembly). As a printer, liquid dispensing device 334 includes a multi-channel printhead assembly 348 supporting multiple print elements 352 (e.g., nozzles, pins, stamps, etc.). Print elements 352 are configured to dispense liquid by depositing droplets at predetermined addresses or spot sites on substrate 104. The liquid dispensing device 334 may also include one or more liquid reservoirs (not shown) for supplying one or more bulk liquids, and one or more liquid flow devices (not shown) and associated liquid flow paths necessary to flow one or more liquids from the liquid reservoirs to and through the print elements 352. Depending on the implementation, such liquid reservoirs and liquid flow devices may be external or internal to the liquid dispensing device 334 as shown schematically.

[0041] In FIG. 3 , the substrate orientation device 200, and in particular the substrate 104, is positioned in a first position (after being moved from another position, if necessary) and moved directly beneath the print elements 352. The vertical gap distance between the print elements 352 and the top surface (112, see FIGS. 1 and 2A) of the substrate 104 is, for example, on the order of microns (e.g., in the range of a few μm to 1000 μm). This gap distance may or may not be adjustable (e.g., by providing vertical adjustment of the print head assembly 348 or the substrate orientation device 200). In applications that do not require all droplets to be printed simultaneously across the entire array of pre-designated spot sites, the array of print elements 352 may be smaller than the sum of the arrays of spot sites. In this case, the print head assembly 348 or the substrate orientation device 200 may be configured to be moved along one or more axes, and multiple print job operations may be performed until the entire array of droplets is printed across the array of spot sites on the substrate 104. Alternatively, the print elements 352 can be arranged in a 2D array having a size (total number of print elements 352 and number of rows and columns of print elements 352) and inter-element spacing that matches the size and spacing of the spots on the substrate 104 where the droplets will be printed (or "written") (see above description of Figure 1), so that certain steps in the printing of droplets of a particular material do not require movement of either the print head assembly 348 or the substrate orientation device 200 relative to one another.

[0042] In one embodiment, the substrate orienting device 200, and in particular the substrate 104, is positioned under the print elements 352 with high precision and high repeatability. This is particularly important for drop-on-drop or drop-on-spot accuracy, for example, in a microarray fabrication process involving multiple printing steps that require droplets to be precisely printed directly onto the same spot site where other droplets have already been printed (and may already have dried by evaporation or been substantially removed by bulk fluid processing, such as may be performed in a flow cell, see below with reference to Figures 4A and 4B). In one embodiment, positional accuracy and repeatability are achieved by mounting the substrate orienting device 200 on a high-precision movable stage, as described below.

[0043] In general, no limitations are imposed on the type of liquid dispensing device 344 utilized in conjunction with the substrate orienting device 200 and other devices and systems disclosed herein, or the type of liquid deposited by the liquid dispensing device 344. The type of liquid dispensing device 344 utilized may depend, at least in part, on the type of liquid dispensing (e.g., microarray fabrication) technology being implemented. As will be appreciated by those skilled in the art, example categories or classes of microarray fabrication technologies include, but are not limited to, non-contact printing, contact printing, and techniques utilizing printing as part of in situ (de novo) synthesis of microarrays. When the substrate 104 is initially positioned in the liquid dispensing device 344 to perform droplet deposition, the spots 108 on the substrate 104 may or may not already contain pre-attached or pre-synthesized (bio)molecules or other chemicals. In this example, the liquid dispensing device 344 is configured for non-contact printing, in which case the print elements 352 may be inkjet elements that deposit droplets to build an array of spots 108 on the substrate 104 ( FIG. 1 ). In this case, for example, the printing (or writing) operation may be based on any known or later-developed suitable technology based on phosphoramidite chemistry. Thus, one example of a liquid dispensed by the liquid dispensing device 344 is a solution containing one or more types of nucleoside phosphoramidites. Also in this case, the print head assembly 348 may include a liquid reservoir containing the liquid to be dispensed, a liquid flow device (liquid-moving components such as a pump, a thermal element, a piezoelectric element, etc.), and associated liquid flow paths necessary to dispense a controlled amount of liquid from the print elements 352 onto the substrate 104. Alternatively, bubble-jet printing technology may be utilized. In alternative cases of contact printing, the print elements 352 may be solid pins, slotted pins, microstamps, etc., as will be understood by those skilled in the art. Contact printing may require the printer 344 to be movable to a separate liquid reservoir to enable the contact print elements to pick up the liquid to be dispensed.

[0044] 4A is a side view of substrate orienting device 200 (i.e., together with frame 220 and any components supported by frame 220, such as substrate 104 and substrate holder 228, if present) positioned in another liquid dispensing station, according to an embodiment of the present disclosure. A liquid dispensing device 456 is positioned in the liquid dispensing station. In this example, the liquid dispensing station is a flow cell station, and liquid dispensing device 456 is a flow cell (module or assembly). As a flow cell module, liquid dispensing device 456 includes one or more flow cells 460 (depending on the number of substrates 104 being processed simultaneously), one or more liquid reservoirs (not shown) for supplying one or more bulk liquids, and one or more liquid flow devices (not shown) and associated liquid flow paths necessary to flow one or more liquids from the liquid reservoirs to and through flow cell 460. Depending on the embodiment, such liquid reservoirs and liquid flow devices may be external or internal to liquid dispensing device 456, which is shown schematically.

[0045] In an embodiment, as shown in FIG. 4A , at a flow cell station, frame 220 (together with any components supported by frame 220) is positioned in a position such that frame 220 (or at least substrate 104 supported by frame 220) is (substantially) parallel to a corresponding flow cell 460. Frame 220 may have been moved to the position shown in FIG. 4A from another position, such as the first position shown in FIG. 2A or the further or intermediate position shown in FIG. 2C. In the position shown in FIG. 4A , frame 220 is positioned a distance from flow cell 460 along the Y-axis. This position may be referred to as an “open flow cell position” in that flow cell 460 is not closed or fluidly sealed, but instead is open to the surrounding environment (e.g., as an open recess or cavity).

[0046] In contrast, FIG. 4B is a side view of the substrate orienting device 200 disposed in the same liquid dispensing station as shown in FIG. 4A , after the substrate orienting device 200 has been moved (e.g., from the position shown in FIG. 4A ) toward the flow cell 460 so that the substrate 104 at least partially closes the flow cell 460. This movement is indicated by an arrow in FIG. 4B . The substrate 104 may “partially” close the flow cell 460 in the sense that other components (e.g., the structure of the frame 220, the substrate holder 228, and / or the liquid dispensing device 456) may contribute to the complete closure or fluidic sealing of the flow cell 460 in a liquid-tight or leak-free manner. For example, as will be understood by those skilled in the art, a gasket or other suitable sealing element may be disposed around the periphery of the flow cell 460. In the closed flow cell position, the liquid dispensing device may be operated to apply one or more types of bulk liquid to the substrate 104, particularly to the top surface 112 of the substrate 104 facing the interior of the closed flow cell 460.

[0047] More specifically, in the closed flow cell position, the top surface 112 of each substrate 104, and thus the array of spots 108 (FIG. 1), faces inward toward the interior of the corresponding flow cell 460. In the closed flow cell position, one or more bulk liquids can flow through the flow cell 460 and contact the spots 108. In one embodiment, the flow cell 460 is filled from the bottom up, removing air bubbles from the flow cell 460 and providing uniform coverage of the top surface 112 of the substrate 104. Generally, the type of liquid flowing through the flow cell 460 will depend on the particular method being performed and the stage of the method that is occurring at a given time. Examples of liquids include, but are not limited to, solutions configured to complete the binding of phosphoramidites or other deposited molecules, solutions for preparing biomolecules to accept subsequently deposited molecules, solutions configured to remove non-specifically bound target molecules from the substrate 104, various reagents, solvents, linkers, catalysts, buffers, washing / rinsing solutions, etc.

[0048] To achieve properly aligned, liquid-tight, or leak-free closure of flow cell 460 by substrate 104, substrate orienting device 200, and in particular substrate 104, should be precisely positioned relative to flow cell 460. As noted elsewhere, a movable stage supporting substrate orienting device 200 may be utilized for this purpose. Substrate orienting device 200 and / or associated liquid dispensing systems, such as those described below, may include position sensors (e.g., encoders), as described below, to improve the positional accuracy and repeatability of operations in liquid dispensing device 456.

[0049] Thus, in an embodiment of substrate orienting device 200, frame 220 is configured to move to an open flow cell position (FIG. 4A) in which frame 220, or at least substrate 104 while supported by frame 220, is parallel to flow cell 460. Additionally, frame 220 is configured to move from the open flow cell position (FIG. 4A) to a closed flow cell position (FIG. 4B) in which substrate 104 while supported by frame 220 at least partially closes flow cell 460.

[0050] Depending on the position of the substrate orientation device 200 relative to the liquid dispensing device 456 during a certain operation, the above-described "second position" of the substrate orientation device 200 shown in FIG. 2B can correspond, for example, to the open flow cell position shown in FIG. 4A or the closed flow cell position shown in FIG. 4B.

[0051] Accordingly, in some embodiments of the substrate orienting device 200, the frame 220 is configured to move to a loading position where the substrate 104 can be loaded onto the frame 220. Additionally, the frame 220 is configured to move to an open flow cell position (FIG. 4A) where the frame 220, or at least the substrate 104 while loaded onto the frame 220, is parallel to the flow cell 460. Additionally, the frame 220 is configured to move from the open flow cell position (FIG. 4A) to a closed flow cell position (FIG. 4B) where the substrate 104 while supported by the frame 220 at least partially closes the flow cell 460.

[0052] The "mounting position" may correspond to the above-described "first position" shown in Figure 2A or Figure 3, or may correspond to a further position oriented at an angle to the first position, such as shown in Figure 2C.

[0053] In an embodiment, movement of frame 220 to the loaded position, open flow cell position, closed flow cell position, etc. can be controlled by a suitable controller. An example of a controller 600 is described below with reference to Figures 6 and 7.

[0054] For purposes of describing certain embodiments, the liquid dispensing device 334 shown in FIG. 3 may be referred to as the "first" liquid dispensing device, and the liquid dispensing device 456 shown in FIGS. 4A and 4B may be referred to as the "second" liquid dispensing device.

[0055] 5A-5C are perspective views of an example liquid dispensing system 500 according to an embodiment of the present disclosure. The liquid dispensing system 500 includes a substrate orientation device (in this example, the substrate orientation device 200 shown in FIGS. 2A-4B ), a first liquid dispensing device 344 disposed at a first liquid dispensing station, and a second liquid dispensing device 456 disposed at a second liquid dispensing station. In this example, the first liquid dispensing device 344 corresponds to the printer disposed at the print station shown in FIG. 3 , and the second liquid dispensing device 456 corresponds to the device disposed at the flow cell station shown in FIGS. 4A and 4B .

[0056] FIG. 5A shows substrate orientation device 200 (or more specifically substrate 104) oriented in a first position, as described above and shown in FIGS. 2A and 3, which may be referred to as a first liquid dispensing position. FIG. 5A also shows substrate orientation device 200 positioned in first liquid dispensing device 344. FIG. 5B shows substrate orientation device 200 (or more specifically substrate 104) oriented in the first position but positioned in second liquid dispensing device 456. For example, liquid dispensing system 500 may have moved (or transported) substrate orientation device 200 from first liquid dispensing device 344 to second liquid dispensing device 456, as indicated by the arrow in FIG. 5B. FIG. 5C shows substrate orientation device 200 (or more specifically substrate 104, not shown) oriented in a second position while positioned in second liquid dispensing device 456, as described above and shown in FIGS. 2B, 4A, and 4B. For example, the substrate orienting device 200 may have moved the frame 220 and the substrate 104 from a first position shown in Figure 5B to a second position shown in Figure 5C. When the substrate 104 is disposed in the second position shown in Figures 4B and 5C, in particular, the second position may be referred to as a second fluid dispensing position, and in this example may also be referred to as a closed flow cell position.

[0057] The liquid dispensing system 500 is configured to move (transport) the substrate orienting device 200 (and thus the substrate 104 supported thereon) to at least the positions shown in FIGS. 5A-5C. To this end, in the illustrated example, the liquid dispensing system 500 includes a stage assembly 580 (or motion control system) configured to move (e.g., linearly translate) the substrate orienting device 200 along one or more axes. In the illustrated example, the stage assembly 580 includes an X-axis (or first axis) drive assembly 502 and a Y-axis (or second axis) drive assembly 506. The X-axis drive assembly 502 is configured to move the substrate orienting device 200 back and forth along the X-axis direction, particularly to and between the first liquid dispensing device 344 ( FIG. 5A ) and the second liquid dispensing device 456 ( FIG. 5B ). The Y-axis drive assembly 506 is configured to move the substrate orienting device 200 back and forth along the Y-axis direction, which may be useful for a variety of functions. For example, the Y-axis drive assembly 506, in conjunction with the X-axis drive assembly 502, may be utilized to accurately and repeatedly position the substrate orienting device 200 (and thus the substrate 104) at the correct location in the X-Y plane relative to the first liquid dispensing device 344 and / or the second liquid dispensing device 456. As another example, the Y-axis drive assembly 506 may be utilized to move the frame 220 and the substrate 104 supported thereon back and forth between the open and closed flow cell positions shown in FIGS. 4A and 4B, respectively. As another example, the Y-axis drive assembly 506 may be useful to facilitate loading and / or unloading of the substrate 104 onto and / or from the substrate orienting device 200 by a user or robot. Such Y-axis positioning may be performed in addition to, or instead of, moving the frame 220 to a dedicated loading position, as in the example shown in FIG. 2C. The stage assembly 580 may also include a Z-axis (or third axis) drive assembly (not shown) to enable vertical adjustment or positioning of the substrate 104 relative to the first liquid dispensing device 344 and / or the second liquid dispensing device 456, if desired.

[0058] In the illustrated example, the substrate orienting device 200 is supported on the Y-axis drive assembly 506 by movable components of the Y-axis drive assembly 506, e.g., a stage, plate, carriage, or other structure, that connect the substrate orienting device 200 to one or more other movable components of the Y-axis drive assembly 506 such that the substrate orienting device 200 moves with the movable components of the Y-axis drive assembly 506. Additionally, the Y-axis drive assembly 506 is supported on the X-axis drive assembly 502 by movable components of the X-axis drive assembly 502, e.g., a stage, plate, carriage, or other structure, that connect the Y-axis drive assembly 506 to one or more other movable components of the X-axis drive assembly 502 such that the Y-axis drive assembly 506 (and thus the substrate orienting device 200) moves with the movable components of the X-axis drive assembly 502. More generally, those skilled in the art will understand that various other alternative configurations of the stage assembly 580 as a motion control system can be implemented to achieve controlled movement of the substrate orientation device 200 in the X direction, or even in the Y direction, or even in the Z direction.

[0059] In the illustrated example, liquid dispensing system 500 includes a deck (or table, workbench, optical bench, platform, base, etc.) 510 upon which various components of liquid dispensing system 500 are supported. Such components may be fixed or attached to deck 510, or may simply rest on deck 510. Deck 510 may be configured to dampen vibrations caused by certain components of liquid dispensing system 500. Depending on the embodiment, deck 510 may be considered part of liquid dispensing system 500 or may be considered separate from liquid dispensing system 500. Additionally, all or a portion of liquid dispensing system 500 may be enclosed by a suitable enclosure (not shown).

[0060] The order or sequence of movements of the substrate orienting device 200 performed by the liquid dispensing system 500 (particularly the stage assembly 580), and the number of times one or more of these movements are repeated or periodically repeated during a certain operating procedure (the number of repetitions), as well as the order or sequence of movements of the frame 220 and the substrate 104 relative to the base 216 of the substrate orienting device 200, and the number of times one or more of these movements are repeated or periodically repeated during a certain operating procedure (the number of repetitions), depend on the particular application or method being implemented.

[0061] FIG. 6 is a front view of an example liquid dispensing system 600 according to another embodiment of the present disclosure. Liquid dispensing system 600 may be similar to liquid dispensing system 500 described above and illustrated in FIGS. 5A-5C. Thus, in the example of FIG. 6, liquid dispensing system 600 includes a substrate orientation device (such as substrate orientation device 200 shown in FIGS. 2A-4B), a first liquid dispensing device disposed at a first liquid dispensing station (such as liquid dispensing device 344 shown in FIG. 3), and a second liquid dispensing device disposed at a second liquid dispensing station (such as liquid dispensing device 456 shown in FIGS. 4A and 4B). As mentioned above, first liquid dispensing device 344 may be or may include a printer, and second liquid dispensing device 456 may be or may include a flow cell assembly.

[0062] Depending on the type of device, first liquid dispensing device 344 may include one or more liquid reservoirs 664 and liquid flow devices 668, which may or may not be integrated with the main structure of first liquid dispensing device 344. Depending on the type of device, second liquid dispensing device 456 may include one or more liquid reservoirs 672 and liquid flow devices 676, which may or may not be integrated with the main structure of flow cell assembly 456.

[0063] The liquid dispensing system 600 also includes a stage assembly 680 configured to move (e.g., linearly translate) the substrate orienting device 200 along one or more axes. The stage assembly 680 may be similar to the stage assembly 580 described above and illustrated in FIGS. 5A-5C and, therefore, may include an X-axis (first axis) drive assembly 602 and a Y-axis (second axis) drive assembly 606. In this example, the stage assembly 680 includes a movable stage 684 on which the substrate orienting device 200 is mounted, the movable stage 684 having a generally plate shape. Alternatively, the movable stage 684 may be embodied as a non-plate-shaped component connected to the base 216 of the substrate orienting device 200. Alternatively, the base 216 itself may function as or be considered to be the movable stage 684, in which case a separate movable stage may not be provided. Those skilled in the art will understand that various other alternative configurations of the stage assembly 680 as a motion control system may be implemented to achieve controlled movement of the substrate orienting device 200 along one or more desired axes.

[0064] In this example, X-axis drive assembly 602 includes an X-axis drive 688 (e.g., including a bidirectional stepper motor or a servo motor) through a linear guide and transmission linkage 692 (e.g., a belt and pulleys, a chain and cogs, a screw and worm gear, etc.). In this example, a movable stage 684 is coupled to X-axis drive 688. Thus, as shown by the double arrow in FIG. 6 , movable stage 684 is configured to move (transport) substrate orienting device 200 (and thus substrate 104) to and between first liquid dispensing device 344 and second liquid dispensing device 456 (e.g., to and between first liquid dispensing station and second liquid dispensing station). The movable stage 684 may also be configured to move the substrate orienting device 200 along the Y-axis at the first or second liquid dispensing station, or both, through operation of the Y-axis drive assembly 606, for purposes such as those described above with respect to the liquid dispensing system 500 shown in FIGS. 5A-5C. In this example, the Y-axis drive assembly 606 includes one or more Y-axis drives 696 (e.g., including one or more bidirectional stepper motors or servo motors) and associated linear guides and transmission linkages 698. As previously mentioned, the stage assembly 680 may further include hardware (not shown) for enabling Z-axis movement to enable vertical adjustment of the substrate 104 relative to the first liquid dispensing device 344 and / or the second liquid dispensing device 456.

[0065] To improve positioning accuracy and repeatability, substrate orientation device 200, first liquid dispensing device 344, second liquid dispensing device 456, and / or associated liquid dispensing system 500 or 600 may also include position sensors (e.g., encoders) 614 configured to detect, measure, and / or track the position of substrate 104, substrate orientation device 200, stage 684, and / or other movable or repositionable devices or equipment. By way of example, one or more position sensors 614 may be configured to assist in properly aligning substrate 104 with first liquid dispensing device 344 and / or second liquid dispensing device 456. Some examples of possible locations for position sensors 614 are shown schematically in FIG. 6. The use of position sensors 614 in coordination with movable / repositionable components of a system or assembly is generally understood by those skilled in the art. The position sensor 614 may be utilized, for example, to measure the position of the substrate 104 relative to a coordinate system (e.g., considering one or more X-, Y-, Z-, and θ-axes), determine whether the substrate position has changed (deviation) compared to a previous iteration of the same operational step, calibrate components responsible for moving or adjusting the substrate position, etc. Generally, the position sensor 614 can be of any suitable type and is often an optical device. For example, the position sensor can include a light source (e.g., a laser, a laser diode (LD), a light-emitting diode (LED), a broadband lamp, etc.) and a photodetector (e.g., a photodiode (PD), a photomultiplier tube (PMT), a camera, etc.), or even other optical components (e.g., lenses, mirrors, etc.). Optionally, the one or more position sensors 614 can detect features on the substrate 104, such as fiducial marks, features on the substrate holder 228, or encoder positions. Additionally, one or more position sensors 614 may be positioned to direct a light beam to intersect the path of droplets dispensed by the print elements 352 of the first liquid dispensing device 344, thereby enabling detection of ejection failure by one or more of the print elements 352 (e.g., due to clogging or failure).

[0066] As explained above, substrate holder 228 may be a vacuum-powered device (e.g., a vacuum chuck), in which case liquid dispensing system 600 includes one or more vacuum sources 618 suitably mounted in fluid communication with substrate holder 228.

[0067] Liquid dispensing system 600 (or 500) can also include a system controller (or controller, or computing device) 700. System controller 700 can generally represent one or more modules (or units, or components) configured to control, monitor, and / or time various functional aspects of liquid dispensing system 600 (or 500), including, for example, the operation of substrate orienting device 200, first liquid dispensing device 344, second liquid dispensing device 456, and stage assembly 680. For all of these purposes, system controller 700 can be in wired or wireless communication with one or more of the components of liquid dispensing system 600 (or 500), as shown by the dashed lines in FIG. 6, and can include any suitable combination of hardware, firmware, software, etc., including one or more electronic-based processors and memory, as will be understood by those skilled in the art. For example, system controller 700 can include a non-transitory (or tangible) computer-readable medium containing non-transitory instructions for performing any of the methods disclosed herein. Further examples of system controller 700 are described below in conjunction with FIG.

[0068] Additional examples of liquid dispensing systems (eg, 500 or 600, see FIGS. 5A-6) according to the present disclosure are described below.

[0069] In an embodiment, the liquid dispensing system includes a substrate orientation device, such as substrate orientation device 200 described above in connection with Figures 2A-4B. The liquid dispensing system may further include one or more liquid dispensing devices (e.g., 344 and / or 456, see Figures 3-6) configured to dispense liquid onto substrate 104 while substrate 104 is supported by the substrate orientation device (e.g., frame 220 of substrate orientation device 200).

[0070] In an embodiment, the frame (and thus any substrate supported by the frame) is movable to a mounting position (e.g., a first position as shown in FIG. 2A, a further position as shown in FIG. 2C, etc.), in which the substrate can be mounted to the frame.

[0071] In embodiments, the liquid dispensing device can be configured to apply bulk liquid to a substrate while the substrate is supported by the frame. For example, as described above, the liquid dispensing device can be or include a flow cell configured to receive a substrate while the substrate is supported by the frame. The frame can be movable to an open flow cell position, in which the frame, or at least the substrate while supported by the frame, is adjacent to (or even parallel to) the flow cell. The frame can also be movable to a closed flow cell position, in which the substrate while supported by the frame at least partially closes the flow cell.

[0072] In another embodiment, the liquid dispensing device can be configured to deposit droplets onto the substrate while the substrate is supported by the frame. For example, as described above, the liquid dispensing device can be or include a printer.

[0073] In embodiments, the liquid dispensing system can include at least a first liquid dispensing device (e.g., 344, see FIGS. 5A-6) configured to dispense a first liquid onto the substrate while the substrate is supported by the frame, and a second liquid dispensing device (e.g., 456, see FIGS. 5A-6) configured to dispense a second liquid onto the substrate while the substrate is supported by the frame. As described above, the first liquid dispensing device can be configured to deposit multiple droplets of the first liquid onto the substrate (as in a printer), and the second liquid dispensing device can be configured to apply a bulk liquid to the substrate as the second liquid (as in a flow cell).

[0074] In embodiments, the liquid dispensing system can include a stage (see, e.g., FIGS. 5A-6) configured to move the substrate orientation device to and between the first and second liquid dispensing devices. The stage can be configured to move along one or more axes (e.g., the X-axis, the X-axis and the Y-axis, or even the Z-axis). In such embodiments, the substrate orientation device can be mountable or coupled to the stage in an appropriate manner and moveable therewith. One or more substrates can be mounted to the substrate orientation device (e.g., its frame) before or after mounting the substrate orientation device to the stage.

[0075] In an embodiment, the liquid dispensing system can include a controller configured to control the movement of the frame relative to the base and / or the movement of the substrate orienting device to and / or from the liquid dispensing device. In an embodiment, the substrate remains supported by the frame during and between the movements of the frame and the substrate orienting device. In other words, the substrate does not need to be removed from the substrate orienting device at any time during the performance of all of these movement tasks.

[0076] In an embodiment, the liquid dispensing system can include a controller configured to control the operation of depositing droplets onto the substrate while supported by the frame and / or applying bulk liquid to the substrate while supported by the frame. As described above, the droplets can be deposited as an array of droplets onto an array of corresponding sites (or addressable locations) on the substrate. In an embodiment, the substrate remains supported by the frame during and between the deposition of the droplets and the application of the bulk liquid. In other words, when performing these two types of liquid dispensing tasks sequentially, the substrate does not need to be removed from the substrate orienting device at any point during the sequence.

[0077] In an embodiment, the liquid dispensing system may include a controller configured to control operations including at least one of the following moving steps: moving the frame to a mounting position where a substrate can be mounted to the frame; moving the frame to an open flow cell position where the frame, or at least the substrate while supported by the frame, is parallel to the flow cell; and / or moving the frame to a closed flow cell position where the substrate while supported by the frame at least partially closes the flow cell.

[0078] In an embodiment, a liquid dispensing system can include a controller configured to control operations including: (a) operating a substrate orientation device to move a substrate to a first liquid dispensing position while the substrate is supported by the substrate orientation device; (b) moving the substrate orientation device to the first liquid dispensing device; (c) dispensing a first liquid onto the substrate at the first liquid dispensing position while the substrate is at the first liquid dispensing position; (d) moving the substrate orientation device from the first liquid dispensing device to a second liquid dispensing device; (e) operating the substrate orientation device to move the substrate to a second liquid dispensing position oriented at an angle relative to the first liquid dispensing position; and (f) dispensing a second liquid onto the substrate at the second liquid dispensing device while the substrate is at the second liquid dispensing position. The order or sequence of steps (a)-(f) can vary depending on the embodiment. For example, the substrate may be moved from one position to another (eg, relative to the base of the substrate orienting device) before or after moving the substrate (together with the substrate orienting device) to a particular liquid dispensing device.

[0079] In embodiments, between any two of steps (a)-(f), the operation is performed without removing the substrate from the substrate orienting device, i.e., the operation, or at least steps (a)-(f) thereof, can be performed entirely without ever removing (or needing to remove) the substrate from the frame.

[0080] FIG. 7 is a schematic diagram of a system controller 700 for a liquid dispensing system (e.g., 500 or 600) according to an embodiment of the present disclosure. All or a portion of controller 700 can correspond to controller 700 described above in conjunction with FIG. 6. Controller 700 can generally represent one or more modules, control units, components, etc. configured to control, monitor, analyze, and / or time the operation of various devices or components of liquid dispensing system 500 or 600, and to control or perform one or more steps of any of the methods disclosed herein. In addition to the various controllable devices or components described above in conjunction with FIGS. 2A-6, other devices may include, but are not limited to, power supplies (voltage sources), timing controllers, clocks, frequency / waveform generators, processors, logic circuits, memories, databases, etc. One or more modules of controller 700 can be or be embodied in one or more devices located external to or separate from the liquid dispensing system (e.g., 500 or 600), such as a computer workstation, desktop computer, laptop computer, portable computer, tablet computer, handheld computer, mobile computing device, personal digital assistant (PDA), smartphone, etc. As will be appreciated by those skilled in the art, one or more modules of controller 700 may communicate with one or more other modules via one or more buses or other types of communication lines or wireless links.

[0081] In the illustrated embodiment, the controller 700 includes one or more electronic-based processors 702, which may represent a main electronic processor providing overall control, and one or more electronic processors (e.g., graphics processing units (GPUs), digital signal processors (DSPs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), etc.) configured for dedicated control operations or specific signal processing tasks. The controller 700 also includes one or more memories 704 (of the volatile and / or non-volatile variety, e.g., RAM and / or ROM) for storing data and / or software. The stored data may be organized, for example, into one or more databases or look-up tables. The controller 700 may also include one or more device drivers 706 for controlling one or more types of user interface devices and providing an interface between the user interface devices and components of the controller 700 that communicate with the user interface devices. Such user interface devices may include user input devices 708 (e.g., keyboard, keypad, touch screen, mouse, joystick, trackball, etc.) and user output devices 710 (e.g., display screen, printer, visual indicators or alerts, audible indicators or alerts, etc.). In various embodiments, controller 700 may be considered to include, or at least be in communication with, one or more of user input devices 708 and / or user output devices 710.

[0082] In some embodiments, controller 700 can also include one or more types of computer programs or software contained in memory and / or on one or more types of non-transitory (or tangible) computer-readable media. One or more devices of controller 700 can be configured to receive and read (and optionally write) computer-readable media. The computer programs or software can include non-transitory instructions (e.g., logic instructions) for controlling or executing various operations of liquid dispensing system 500 or 600, such as the operation of the various devices described herein. The computer programs or software can include system software and application software. The system software can include an operating system (e.g., a Microsoft Windows® operating system) for controlling and managing various functions of controller 600, including the interaction between hardware and application software. In particular, the operating system can provide a graphical user interface (GUI) displayable via user output device 710, and a user can interact with this GUI using user input device 708. The application software can include software configured to control or perform various operations of liquid dispensing system 500 or 600 and / or some or all of the steps of any of the methods disclosed herein.

[0083] Controller 700 may also include a first liquid dispensing device (e.g., printer) controller (or control module) 712 configured to control the operation of first liquid dispensing device 344, a second liquid dispensing device (e.g., flow cell) controller (or control module) 714 configured to control the operation of first liquid dispensing device 456, and a motion or stage controller (or control module) 716 configured to control the operation of stage assembly 580 or 680 (see FIGS. 5A-5C and 6). Controller 700 may also include one or more sensor interfaces 718 configured to receive and process feedback (e.g., measurement) signals received from one or more sensors provided in liquid dispensing system 500 or 600, such as position sensor 614 (FIG. 6) described above. For example, sensor interface 718 may be embodied in separate firmware or other electronic circuitry that is part of a microcontroller of controller 700. Sensor interface 718 may communicate with first liquid dispensing device controller 712, second liquid dispensing device controller 714, and motion controller 716 as needed to effectively control various operations of liquid dispensing systems 500 or 600 described herein. Firmware or other electronic circuitry embodying first liquid dispensing device controller 712, second liquid dispensing device controller 714, and motion controller 716 may be provided on the same microcontroller that includes sensor interface 718, or may be provided on separate hardware of controller 700.

[0084] Further examples of methods for dispensing liquid onto a substrate according to the present disclosure are now described. One or more of the methods can utilize a substrate orientation device (e.g., 200, see FIGS. 2A-4B) and / or a liquid dispensing system (e.g., 500 or 600, see FIGS. 5A-6), which can include one or more liquid dispensing devices (e.g., 344 and / or 456, see FIGS. 3-6), according to any of the embodiments described herein.

[0085] FIG. 8 is a flow chart 800 illustrating an example method for dispensing a liquid onto a substrate according to an embodiment of the present disclosure. In the method, a substrate orientation device is provided (step 802). As described above, the substrate orientation device includes a base and a frame configured to support a substrate. The substrate is attached to the frame (step 804). Two or more substrates may be attached and then processed simultaneously as described above. Prior to attachment of the substrate, the substrate may be prepared for the liquid dispensing operation as needed for the particular method being performed. For example, the substrate may be prepared as needed for fabricating a particular (bio)chemical microarray. Next, the frame (with the substrate attached) is moved to a first position where the frame is substantially parallel to the base (step 806). Next, the frame is moved to a second position where the frame is oriented at an angle relative to the base (step 808). Liquid is dispensed onto the substrate either before or after moving the frame to the first and second positions (step 810). For example, liquid may be dispensed onto the substrate while the substrate is oriented in a first position and / or a second position, depending on the particular method being performed.

[0086] In embodiments, the method can include dispensing a first liquid onto a substrate and dispensing a second liquid onto the substrate. Dispensing the first liquid can involve depositing multiple droplets onto the substrate. Dispensing the second liquid can involve applying a bulk liquid to the substrate. Dispensing the first liquid can be performed by a first liquid dispensing device, and dispensing the second liquid can be performed by a second liquid dispensing device (e.g., a device different from or separate from the first liquid dispensing device).

[0087] In an embodiment, dispensing a first liquid occurs while the substrate is oriented at the first liquid dispensing position and the substrate orientation device is at the first liquid dispensing device. The substrate orientation device can then be moved from the first liquid dispensing device to the second liquid dispensing device. The substrate can then be moved to the second liquid dispensing position (e.g., from the first liquid dispensing position to the second liquid dispensing position) by moving the frame. Dispensing a second liquid occurs while the substrate is oriented at the second liquid dispensing position and the substrate orientation device is at the second liquid dispensing device.

[0088] In an embodiment, moving the substrate orienting device occurs between dispensing the first liquid and dispensing the second liquid and occurs without removing the substrate from the frame.

[0089] FIG. 9 is a flow chart 900 illustrating another example of a method for dispensing a liquid onto a substrate according to an embodiment of the present disclosure. In the method, a substrate is loaded onto a substrate orientation device (step 902). As described above, the substrate orientation device can include a base and a frame configured to support the substrate. Two or more substrates may be loaded and then processed simultaneously as described above. Prior to loading the substrate, the substrate may be prepared for a liquid dispensing operation depending on the application, as described above. Next, the substrate orientation device is operated to move the substrate to a first liquid dispensing position (step 904). Next, the substrate orientation device is moved to the first liquid dispensing device (step 906). At the first liquid dispensing device, a first liquid is dispensed onto the substrate (step 908). Next, the substrate orientation device is moved from the first liquid dispensing device to a second liquid dispensing device (step 910). The substrate orientation device is then operated to move the substrate to a second liquid dispensing location oriented at an angle relative to the first liquid dispensing location (step 912). At the second liquid dispensing device, a second liquid is dispensed onto the substrate (step 914).

[0090] In embodiments, between any two of steps 902-914, the method is performed without removing the substrate from the substrate orienting device. After loading the substrate, all steps 904-914 can be performed while the substrate remains on the same frame (or same substrate holder). In other words, in embodiments, the substrate does not need to be removed from the frame or substrate holder until the liquid dispensing (e.g., microarray fabrication) process is complete (at least until steps 902-914 are complete). Furthermore, during the liquid dispensing process, the substrate does not need to be removed and later reloaded, either to the same frame or substrate holder or to a different frame or substrate holder.

[0091] As described elsewhere in this disclosure, in either method, multiple steps (iterations) of liquid dispensing operations (e.g., droplet deposition and bulk liquid flow) can be performed as needed for the particular method being implemented. To this end, the substrate orientation device can be moved back and forth between two or more liquid dispensing devices (e.g., between the printer and the flow cell assembly) as many times as needed.

[0092] In an embodiment, one or more steps of the methods described and illustrated in Figures 8 and 9 may be controlled or performed by a controller including a processor, memory, and other components that would be understood by one skilled in the art, such as controller 700 described above in conjunction with Figure 6 or Figure 7.

[0093] In embodiments, flowcharts 800 and / or 900 may represent a substrate orientation device or even a liquid dispensing system configured to perform the steps shown in flowcharts 800 and / or 900. To this end, various components of the substrate orientation device and / or liquid dispensing system described herein may be utilized.

[0094] Implementations of the subject matter disclosed herein (i.e., substrate orienting device 200, or substrate orienting device 200 in conjunction with liquid dispensing system 500 or 600, and methods for dispensing liquid onto substrates, e.g., for microarray fabrication, etc.) can provide one or more advantages. One advantage is that it eliminates the need to remove / transfer / re-attach substrate 104 from one frame or substrate holder to another (different) substrate holder. This eliminates the need for a robotic arm to perform the swapping operation and the need for constant reliance on machine vision for theta alignment axis (i.e., rotation about one or more of the X-axis, Y-axis, and Z-axis) and substrate realignment. In the implementations described herein, a single frame or substrate holder can handle operations while the corresponding substrate is in any position or orientation, including a horizontal orientation optimal for droplet deposition and a vertical orientation optimal for flow cell processing.

[0095] Exemplary Implementations Exemplary embodiments provided in accordance with the presently disclosed subject matter include, but are not limited to, the following.

[0096] 1. A substrate orientation device for orienting a substrate configured as a solid support for liquid dispensing, the substrate orientation device comprising: a base; and a frame configured to support the substrate and move to a first position and a second position relative to the base, wherein in the first position the substrate is substantially parallel to the base while supported by the frame, and in the second position the substrate is oriented at an angle relative to the base while supported by the frame.

[0097] 2. A substrate orienting device as described in embodiment 1, comprising at least one of the following configurations: in the second position, the substrate is substantially perpendicular to the base while supported by the frame; the frame is movable to a further position different from the first position and the second position; the frame is movable to a further position where the substrate is substantially perpendicular to the base while supported by the frame; the frame is movable to a further position oriented at an angle between the first position and the second position; the frame is rotatable to at least one of the first position, the second position, and a further position different from the first position and the second position; and at least one of the base or the frame is linearly translatable to at least one of the first position, the second position, and a further position different from the first position and the second position.

[0098] 3. A substrate orienting device as described in embodiment 1 or 2, comprising at least one of: the frame is movable to an attachment position in which a substrate can be attached to the frame; the frame is movable to an open flow cell position in which the frame, or at least the substrate while supported by the frame, is adjacent to the flow cell; the frame is movable to a closed flow cell position in which the substrate while supported by the frame at least partially closes the flow cell; and the frame is movable from the open flow cell position to a closed flow cell position, in which in the open flow cell position, the frame, or at least the substrate while supported by the frame, is adjacent to the flow cell, and in the closed flow cell position, the substrate while supported by the frame at least partially closes the flow cell.

[0099] 4. A substrate orientation device according to any one of the preceding embodiments, comprising an actuator configured to drive movement of the frame relative to the base.

[0100] 5. A substrate orientation device as described in embodiment 4, comprising a coupling device that couples the actuator to at least one of the base and the frame, the actuator being configured to drive movement of the frame via the coupling device.

[0101] 6. A substrate orientation device as described in embodiment 5, wherein the coupling device comprises one of the following configurations: the coupling device comprises an axis; the coupling device comprises an axis support; the coupling device comprises a rotatable axis, the frame configured to rotate with the axis; the coupling device comprises a rotatable axis and an axis support, the frame configured to rotate with the axis; the coupling device comprises an axis and a rotatable axis support, the frame configured to rotate with the axis support; the coupling device comprises an axis and an axis support, the axis support being attached to or integral with at least one of the base or the frame.

[0102] 7. A substrate orienting device according to any one of the preceding embodiments, comprising a substrate holder mounted on or integral with the frame and configured to support a substrate.

[0103] 8. A liquid dispensing system comprising: a substrate orienting device according to any one of the preceding embodiments; and a liquid dispensing device configured to dispense a liquid onto the substrate while the substrate is supported by the frame.

[0104] 9. A liquid dispensing system as described in embodiment 8, wherein the liquid dispensing device comprises a flow cell configured to receive a substrate while the substrate is supported by the frame.

[0105] 10. A liquid dispensing system as described in embodiment 9, comprising at least one of: the frame is movable to an attachment position in which a substrate can be attached to the frame; the frame is movable to an open flow cell position in which the frame, or at least the substrate while supported by the frame, is adjacent to the flow cell; the frame is movable to a closed flow cell position in which the substrate while supported by the frame at least partially closes the flow cell; and the frame is movable from the open flow cell position to a closed flow cell position, in which in the open flow cell position, the frame, or at least the substrate while supported by the frame, is adjacent to the flow cell, and in the closed flow cell position, the substrate while supported by the frame at least partially closes the flow cell.

[0106] 11. A liquid dispensing system as described in embodiment 8, wherein the liquid dispensing device is configured to deposit droplets onto the substrate while the substrate is supported by the frame.

[0107] 12. The liquid dispensing system of embodiment 11, wherein the liquid dispensing device includes a printer.

[0108] 13. A liquid dispensing system as described in embodiment 8, wherein the liquid dispensing device is configured to apply bulk liquid to the substrate while the substrate is supported by the frame.

[0109] 14. The liquid dispensing system of embodiment 13, wherein the liquid dispensing device includes a flow cell.

[0110] 15. A liquid dispensing system as described in embodiment 8, further comprising: a first liquid dispensing device configured to dispense a first liquid onto the substrate while the substrate is supported by the frame; and a second liquid dispensing device configured to dispense a second liquid onto the substrate while the substrate is supported by the frame.

[0111] 16. A liquid dispensing system as described in embodiment 15, wherein the first liquid dispensing device is configured to deposit multiple droplets onto the substrate as a first liquid, and the second liquid dispensing device is configured to apply a bulk liquid to the substrate as a second liquid.

[0112] 17. A liquid dispensing system as described in embodiment 15 or 16, comprising a stage configured to move the substrate orienting device between the first liquid dispensing device and the second liquid dispensing device.

[0113] 18. A liquid dispensing system described in any one of embodiments 15 to 17, comprising a controller configured to control operations including: (a) operating a substrate orientation device to move a substrate to a first liquid dispensing position while the substrate is supported by the substrate orientation device; (b) moving the substrate orientation device to the first liquid dispensing device; (c) dispensing a first liquid onto the substrate at the first liquid dispensing device while the substrate is at the first liquid dispensing position; (d) moving the substrate orientation device from the first liquid dispensing device to a second liquid dispensing device; (e) operating the substrate orientation device to move the substrate to a second liquid dispensing position oriented at an angle relative to the first liquid dispensing position; and (f) dispensing a second liquid onto the substrate at the second liquid dispensing device while the substrate is at the second liquid dispensing position.

[0114] 19. A liquid dispensing system as described in embodiment 18, wherein between any two of steps (a) to (f), the operation is performed without removing the substrate from the substrate orienting device.

[0115] 20. A liquid dispensing system described in any one of embodiments 8 to 19, comprising a stage movable along one or more axes, wherein the substrate orientation device is mountable to the stage and movable together with the stage.

[0116] 21. A liquid dispensing system described in any one of embodiments 8 to 20, comprising a controller configured to control operations including one of: moving the frame relative to the base; moving the substrate orientation device to and from the liquid dispensing device; moving the frame relative to the base and moving the substrate orientation device to and from the liquid dispensing device; and moving the frame relative to the base and moving the substrate orientation device to and from the liquid dispensing device, wherein the substrate remains supported by the frame between the movement of the frame and the movement of the substrate orientation device.

[0117] 22. A liquid dispensing system described in any one of embodiments 8 to 21, comprising a controller configured to control operations including at least one of: depositing droplets onto a substrate while supported by a frame; depositing an array of droplets onto an array of corresponding sites on the substrate while supported by the frame; applying bulk liquid to the substrate while supported by the frame; depositing droplets onto the substrate while supported by the frame and applying bulk liquid to the substrate while supported by the frame; and depositing droplets onto the substrate while supported by the frame and applying bulk liquid to the substrate while supported by the frame, wherein the substrate remains supported by the frame between the deposition of the droplets and the application of the bulk liquid.

[0118] 23. A liquid dispensing system described in any one of embodiments 8 to 22, comprising a controller configured to control operations including at least one of: moving the frame to an attachment position in which a substrate can be attached to the frame; moving the frame to an open flow cell position in which the frame or at least the substrate while supported by the frame is parallel to the flow cell; and moving the frame to a closed flow cell position in which the substrate while supported by the frame at least partially closes the flow cell.

[0119] 24. A method for dispensing a liquid onto a substrate, comprising: providing a substrate orienting device according to any one of the preceding embodiments; mounting the substrate in a frame; moving the frame to a first position; moving the frame to a second position; and dispensing the liquid onto the substrate before or after moving the frame to the first and second positions.

[0120] 25. A method for dispensing a liquid onto a substrate, the method comprising: providing a substrate orienting device comprising a base and a frame configured to support a substrate; mounting the substrate to the frame; moving the frame relative to the base to a first position in which the frame is substantially parallel to the base; moving the frame relative to the base to a second position in which the frame is oriented at an angle to the base; and dispensing the liquid onto the substrate before or after moving the frame to the first and second positions.

[0121] 26. The method of embodiment 25, comprising at least one of: moving the frame to a further position oriented at an angle between the first position and the second position; moving the frame to a further position where the substrate is adjacent to the flow cell; moving the frame to a further position, wherein the substrate is mounted at the further position; and wherein the movement of the frame relative to the base comprises rotating the frame and linearly translating at least one of the base or the frame.

[0122] 27. The method of embodiment 25 or 26, comprising moving the frame to an open flow cell position in which the substrate is parallel to the open flow cell, and moving the frame to a closed flow cell position in which the substrate at least partially closes the flow cell.

[0123] 28. The method of embodiment 27, wherein the dispensing of the liquid is performed in a closed flow cell position.

[0124] 29. A method according to any one of embodiments 25 to 28, wherein dispensing a liquid includes dispensing a first liquid onto the substrate and dispensing a second liquid onto the substrate.

[0125] 30. The method of embodiment 29, comprising one of: dispensing the first liquid comprises dispensing a plurality of droplets onto the substrate; dispensing the second liquid comprises applying a bulk liquid onto the substrate; dispensing the first liquid comprises depositing a plurality of droplets onto the substrate; and dispensing the second liquid comprises applying a bulk liquid to the substrate.

[0126] 31. The method of embodiment 29 or 30, wherein the first liquid is dispensed by a first liquid dispensing device and the second liquid is dispensed by a second liquid dispensing device.

[0127] 32. The method of embodiment 31, wherein dispensing the first liquid is performed while the substrate is at the first liquid dispensing position and the substrate orientation device is at the first liquid dispensing device, and the method further includes moving the substrate orientation device from the first liquid dispensing device to a second liquid dispensing device and moving the frame to move the substrate to the second liquid dispensing position, wherein dispensing the second liquid is performed while the substrate is at the second liquid dispensing position and the substrate orientation device is at the second liquid dispensing device.

[0128] 33. The method of embodiment 32, wherein moving the substrate orienting device is performed between dispensing the first liquid and dispensing the second liquid, and is performed without removing the substrate from the frame.

[0129] 34. The method of embodiment 31, comprising: (a) operating a substrate orientation device to move a substrate to a first liquid dispensing position; (b) moving the substrate orientation device to the first liquid dispensing device; (c) dispensing a first liquid onto the substrate at the first liquid dispensing device while the substrate is at the first liquid dispensing position; (d) moving the substrate orientation device from the first liquid dispensing device to a second liquid dispensing device; (e) operating the substrate orientation device to move the substrate to a second liquid dispensing position oriented at an angle relative to the first liquid dispensing position; and (f) dispensing a second liquid onto the substrate at the second liquid dispensing device while the substrate is at the second liquid dispensing position.

[0130] 35. The method of embodiment 34, wherein the method is performed without removing the substrate from the substrate orienting device between any two of steps (a) to (f).

[0131] It will be understood that one or more of the processes, sub-processes, and process steps described herein may be performed on one or more electronic or digitally controlled devices by hardware, firmware, software, or a combination of two or more thereof. The software may reside in a software memory (not shown) in a suitable electronic processing component or system, such as, for example, the system controller 700 schematically represented in FIG. 6 or FIG. 7. The software memory may include an ordered list of executable instructions for performing logical functions (i.e., “logic,” which may be implemented in digital form, such as digital circuitry or source code, or in analog form, such as analog sources, such as analog electrical signals, sound signals, or video signals). The instructions may be executed within a processing module, including, for example, one or more microprocessors, general-purpose processors, combinations of processors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), etc. Furthermore, the schematic diagrams illustrate a logical division of functions, with physical (hardware and / or software) implementation not limited by the architecture or physical layout of the functions. The example systems described herein may be implemented in a variety of configurations and may operate as hardware / software components within a single hardware / software unit or may operate within separate hardware / software units.

[0132] The executable instructions may be embodied as a computer program product having stored thereon the instructions, which, when executed by a processing module of an electronic system (e.g., a system controller 700 shown schematically in FIG. 6 or FIG. 7), direct the electronic system to execute the instructions. The computer program product may be optionally embodied in any non-transitory computer-readable storage medium for use by or in conjunction with an instruction execution system, apparatus, or device, such as an electronic computer-based system, a processor-containing system, or other system capable of selectively fetching instructions from and executing the instructions from an instruction execution system, apparatus, or device. In the context of the present disclosure, a computer-readable storage medium is any non-transitory means capable of storing a program for use by or in conjunction with an instruction execution system, apparatus, or device. The non-transitory computer-readable storage medium may optionally be, for example, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device. A non-exhaustive list of more specific examples of non-transitory computer-readable media includes an electrical connection having one or more wires (electronic), a portable computer diskette (magnetic), a random access memory (electronic), a read-only memory (electronic), an erasable programmable read-only memory such as, for example, flash memory (electronic), a compact disc memory such as, for example, a CD-ROM, a CD-R, a CD-RW (optical), and a digital versatile disc memory, i.e., a DVD (optical). Note that a non-transitory computer-readable storage medium may also be paper or another suitable medium on which a program is printed, since a program may be captured electronically, for example, via optical scanning of paper or other medium, and then compiled, interpreted, or otherwise processed in an appropriate manner as needed, and then stored in computer or machine memory.

[0133] It will also be understood that the terms "in signal communication" or "in electrical communication," as used herein, mean that two or more systems, devices, components, modules, or sub-modules can communicate with each other via signals traveling over some type of signal path. The signals may be communication, power, data, or energy signals, and may communicate information, power, or energy from a first system, device, component, module, or sub-module to a second system, device, component, module, or sub-module along a signal path between the first and second systems, devices, components, modules, or sub-modules. The signal path may include physical, electrical, magnetic, electromagnetic, electrochemical, optical, wired, or wireless connections. The signal path may also include additional systems, devices, components, modules, or sub-modules between the first and second systems, devices, components, modules, or sub-modules.

[0134] More generally, terms such as "communicate" and "in communication" (e.g., a first component "communicates" or "is in communication" with a second component) are used herein to denote a structural, functional, mechanical, electrical, signal, optical, magnetic, electromagnetic, ionic, or fluid relationship between two or more components or elements. Thus, the fact that a component is described as communicating with a second component is not intended to exclude the possibility that additional components may be present between and / or operatively associated with or engaged with the first and second components.

[0135] It will be understood that various aspects or details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for illustrative purposes only and is not intended to limit the invention as defined by the claims.

Claims

1. 1. A substrate orientation device for orienting a substrate configured as a solid support for liquid dispensing, comprising: With the base, a frame configured to support the substrate and move to a first position and a second position relative to the base; Equipped with In the first position, the substrate is substantially parallel to the base while being supported by the frame; In the second position, the substrate is oriented at an angle relative to the base while being supported by the frame.

2. the frame is movable to a mounting position where the substrate can be mounted to the frame; the frame is movable to an open flow cell position in which the frame, or at least the substrate while supported by the frame, is adjacent to a flow cell; the frame is movable to a closed flow cell position in which the substrate, while supported by the frame, at least partially closes a flow cell; the frame is movable from an open flow cell position to a closed flow cell position, in which the frame, or at least the substrate while supported by the frame, is adjacent to a flow cell, and in which the substrate while supported by the frame at least partially closes the flow cell; The substrate orientation device of claim 1 , comprising at least one of:

3. The substrate orientation device of claim 1 , comprising an actuator configured to drive movement of the frame relative to the base.

4. A substrate alignment device according to claim 1; a liquid dispensing device configured to dispense a liquid onto the substrate while the substrate is supported by the frame; A liquid dispensing system comprising:

5. The liquid dispensing system of claim 4 , wherein the liquid dispensing device comprises a flow cell configured to receive the substrate while the substrate is supported by the frame.

6. The liquid dispensing system of claim 4 , wherein the liquid dispensing device is configured to deposit droplets onto the substrate while the substrate is supported by the frame.

7. The liquid dispensing system of claim 4 , wherein the liquid dispensing device is configured to apply bulk liquid to the substrate while the substrate is supported by the frame.

8. the liquid dispensing device is a first liquid dispensing device configured to dispense a first liquid onto the substrate while the substrate is supported by the frame; 5. The fluid dispensing system of claim 4, further comprising a second fluid dispensing device configured to dispense a second fluid onto the substrate while the substrate is supported by the frame.

9. 9. The liquid dispensing system of claim 8, wherein the first liquid dispensing device is configured to deposit a plurality of droplets as the first liquid onto the substrate, and the second liquid dispensing device is configured to apply a bulk liquid to the substrate as the second liquid.

10. The liquid dispensing system of claim 8 , comprising a stage configured to move the substrate orientation device between the first liquid dispensing device and the second liquid dispensing device.

11. (a) operating the substrate orientation device to move the substrate to a first liquid dispensing position while the substrate is supported by the substrate orientation device; (b) moving the substrate orienting device to the first liquid dispensing device; (c) dispensing a first liquid onto the substrate at the first liquid dispensing device while the substrate is at the first liquid dispensing position; (d) moving the substrate orienting device from the first liquid dispensing device to the second liquid dispensing device; (e) operating the substrate orienting device to move the substrate to a second liquid dispensing location oriented at an angle relative to the first liquid dispensing location; (f) dispensing a second liquid onto the substrate at the second liquid dispensing device while the substrate is at the second liquid dispensing position; The liquid dispensing system of claim 8 , comprising a controller configured to control operations including:

12. The liquid dispensing system of claim 11 , wherein the operations are performed without removing the substrate from the substrate orienting device between any two of steps (a)-(f).

13. moving the frame relative to the base; moving the substrate orienting device to and from the liquid dispensing device; moving the frame relative to the base to move the substrate orienting device to and from the liquid dispensing device; moving the frame relative to the base and moving the substrate orienting device to and from the liquid dispensing device, wherein the substrate remains supported by the frame between the movement of the frame and the movement of the substrate orienting device; The liquid dispensing system of claim 4 , comprising a controller configured to control operations including one of:

14. depositing a droplet onto the substrate while supported by the frame; depositing an array of droplets onto an array of corresponding locations on the substrate while supported by the frame; applying a bulk liquid to the substrate while supported by the frame; depositing droplets onto the substrate while supported by the frame and applying bulk liquid to the substrate while supported by the frame; depositing droplets onto the substrate while supported by the frame and applying bulk liquid to the substrate while supported by the frame, the substrate remaining supported by the frame between the deposition of the droplets and the application of the bulk liquid; The liquid dispensing system of claim 4 , comprising a controller configured to control operations including at least one of:

15. moving the frame to a loading position where the substrate can be loaded onto the frame; moving the frame to an open flow cell position in which the frame, or at least the substrate while supported by the frame, is parallel to a flow cell; moving the frame to a closed flow cell position in which the substrate, while supported by the frame, at least partially closes a flow cell; The liquid dispensing system of claim 4 , comprising a controller configured to control operations including at least one of:

16. 1. A method for dispensing a liquid onto a substrate, comprising: providing a substrate orienting device comprising a base and a frame configured to support the substrate; Mounting the substrate on the frame; moving the frame relative to the base to a first position in which the frame is substantially parallel to the base; moving the frame relative to the base to a second position in which the frame is oriented at an angle relative to the base; dispensing a liquid onto the substrate before or after moving the frame to the first position and the second position; A method comprising:

17. 17. The method of claim 16, wherein the dispensing the liquids comprises dispensing a first liquid onto the substrate and dispensing a second liquid onto the substrate.

18. 18. The method of claim 17, wherein the first liquid is dispensed by a first liquid dispensing device and the second liquid is dispensed by a second liquid dispensing device.

19. The dispensing of the first liquid occurs while the substrate is at a first liquid dispensing location and the substrate orienting device is at the first liquid dispensing device, and the method further comprises: moving the substrate orientation device from the first liquid dispensing device to the second liquid dispensing device; moving the substrate to a second liquid dispensing position by moving the frame, wherein the dispensing of the second liquid occurs while the substrate is at the second liquid dispensing position and the substrate orienting device is at the second liquid dispensing device; 20. The method of claim 18, further comprising:

20. 20. The method of claim 19, wherein the moving of the substrate orienting device occurs between the dispensing of the first liquid and the dispensing of the second liquid, and occurs without removing the substrate from the frame.

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