Liquid dispensing device for filling plurality of containers

Abstract

A liquid dispensing device provides an input flow of liquid from a single inlet into an internal manifold, and distributes or divides the input flow from the manifold into a set of separate liquid loops that direct respective output flows to outlets from which controlled volumes of liquid can be dispensed into respective containers, such as pores of a perforated plate. The volume of liquid dispensed into one container may be different from the volume of liquid dispensed into another container. Each liquid circuit may include a valve that regulates liquid flow in the liquid circuit, which may be based on feedback from a flow rate sensor. If desired, two or more liquid dispensing devices may be stacked horizontally to provide additional unique liquid circuits and different liquids.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. patent application serial number 18 / 103,449, filed on January 30, 2023, entitled “LIQUID DISPENSING DEVICE FOR FILLING MULTIPLE CONTAINERS,” under 35 U.S.C. §§ 120, 363, and 365(c), the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present invention generally relates to dispensing a liquid from a source into a plurality of containers, such as into the wells of a multi-well plate.The apparatus for dispensing a liquid can be implemented in laboratory hardware, for example, can be automated. Background Art

[0004] Many methods involving the processing of liquids or liquid-borne materials benefit from the use of liquid handling systems configured for high-throughput processing and utilizing a high degree of automation, particularly systems configured to dispense or fill containers (such as the wells of a multiwell plate). Such processing may involve the parallel detection, measurement, or analysis of a large number of chemical or biological samples, or the synthesis of chemical or biological products from a large number of precursor materials. For dispensing operations, liquid handling systems have been developed that utilize electronic pipette heads or inkjet printer-type heads to dispense small amounts of liquid into the individual wells of a multiwell plate loaded onto such a system. Such known systems may also utilize robotics to load and unload multiwell plates into and from the system. Known systems may exhibit issues with performance, reliability, and high-throughput capabilities. For example, known systems may be overly sensitive to variable conditions that affect liquid flow (such as variable viscosity and clogging events), and may be mechanically complex and / or prone to leaks or other failures. Furthermore, known systems may not be able to perform liquid dispensing operations as quickly as desired and may not be able to perform chemical or biological syntheses or analyses on a sufficiently large scale given the number of samples involved. Furthermore, for systems that rely on the use of single-use (disposable) pipette tips, the additional cost and waste associated with frequent pipette tip replacement is undesirable in certain applications.

[0005] Therefore, further development of liquid dispensing devices, systems, and methods is needed. Summary of the Invention

[0006] To fully or partially meet the above needs, and / or other needs that may have been observed by those skilled in the art, the present disclosure provides methods, processes, systems, devices, instruments and / or apparatus as examples in the embodiments described below.

[0007] In some aspects of the present disclosure, the liquid dispensing device provides a liquid flow from a single inlet to an internal manifold and distributes the liquid from the manifold into a set of unique liquid circuits or channels, which guide the corresponding liquid flow to an outlet, from which controlled volumes of liquid can be distributed to corresponding containers, such as the holes of a multi-well plate, etc. The liquid circuits or channels are defined by corresponding liquid conduits (e.g., tubes, pipes, etc.) that are communicated with a common manifold. Each liquid circuit or channel includes a valve that regulates the liquid flow in the liquid circuit. If desired, two or more liquid dispensing devices can be stacked horizontally to provide additional unique liquid circuits and supply different liquids. The liquid dispensing device can be integrated with a larger system or device (e.g., a laboratory automation tool or instrument) that is configured for liquid distribution and any number of possible other liquid handling tasks (e.g., mixing, dilution, buffering, other types of liquid regulation, (bio) chemical reactions, (bio) chemical synthesis, chemical or enzyme cutting, hybridization, analytical separation and / or collection of sample components, purification, detection / measurement of analytes, etc.).

[0008] According to one embodiment, a liquid distribution device includes: a shell surrounding an interior of the device; a manifold, which is arranged inside the device and includes an inlet; a plurality of conduits, which are arranged inside the device and connected to the manifold and respectively include a plurality of horizontally spaced outlets; and a plurality of actively controllable valves respectively arranged in the conduits, which are configured to control the corresponding liquid flows through the conduits, wherein the liquid distribution device defines a common liquid input flow path in the manifold, and a plurality of liquid output flow paths extending from the manifold through the corresponding conduits and reaching the corresponding outlets.

[0009] In an embodiment, the liquid dispensing device includes one or more flow rate sensors configured to measure the flow rate in the common liquid input flow path and / or the flow rate in the output flow path. As an example, the measurement data generated by the flow rate sensors can be used to adjust the flow rate in one or more of the conduits and / or the volume dispensed from one or more of the conduits.

[0010] According to another embodiment, a liquid dispensing system comprises: a plurality of liquid dispensing devices according to any one of the embodiments disclosed herein, wherein the liquid dispensing devices are stacked horizontally such that outlets of the liquid dispensing devices are arranged in a two-dimensional array.

[0011] According to another embodiment, a liquid dispensing system includes: one or more liquid dispensing devices according to any of the embodiments disclosed herein; and a stage movable along one or more axes, which is configured to move multiple containers (e.g., multiwell plates) to and from the liquid dispensing device.

[0012] According to another embodiment, a method for dispensing liquid includes: providing a liquid dispensing device, which includes a manifold, a plurality of conduits, and a plurality of valves respectively arranged in the conduits, wherein the manifold includes an inlet and the plurality of conduits respectively include a plurality of outlets; providing a plurality of containers; selecting a selected container from the plurality of containers to receive the liquid; determining the volume of the liquid to be respectively dispensed into the selected containers, wherein the volume determined for at least one of the selected containers is different from the volume determined for at least another of the selected containers; allowing the liquid to flow through the inlet and the manifold and into the conduits; and dispensing the liquid from the corresponding outlets of the plurality of outlets into the selected containers according to the determined volume by controlling the valves.

[0013] According to another embodiment, a method for dispensing liquid includes: providing a liquid dispensing device, the liquid dispensing device including a manifold, a plurality of conduits, and a plurality of valves respectively arranged in the conduits, wherein the manifold includes an inlet and the plurality of conduits respectively include a plurality of outlets; dispensing liquid from one or more selected conduits of the plurality of conduits; measuring the corresponding flow rate of the liquid in the selected conduits; for each selected conduit, determining whether the measured flow rate deviates from a target flow rate or a target flow rate range set for the selected conduit; for each selected conduit in which the measured flow rate is determined to deviate from the target flow rate or the target flow rate range for the selected conduit, adjusting the valve operation of the valve in the selected conduit.

[0014] In an embodiment, the dispensing of the determined volume comprises controlling a valve based on one or more flow rates measured in the inlet and / or the manifold and / or the one or more conduits.

[0015] According to another embodiment, a non-transitory computer readable medium includes instructions stored thereon that, when executed on a processor, control or perform one or more of the selecting, flowing, and dispensing steps according to any of the methods disclosed herein.

[0016] According to another embodiment, a liquid dispensing system includes a non-transitory computer-readable storage medium.

[0017] Other devices, apparatus, systems, methods, features and advantages of the present invention will become apparent to those skilled in the art upon examination of the following drawings and detailed description. All such additional systems, methods, features and advantages are intended to be included within this description, be within the scope of the present invention, and be protected by the following claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The present invention may be better understood by reference to the following drawings. The components in the drawings are not necessarily drawn to scale, emphasis being placed on illustrating the principles of the present invention. In the drawings, like reference numerals denote corresponding parts in different views.

[0019] Figure 1is a schematic diagram of an example of a liquid dispensing device according to an embodiment of the present disclosure.

[0020] Figure 2 is a perspective view of an example of a multiwell plate that may be used with a liquid dispensing apparatus according to an embodiment of the present disclosure.

[0021] Figure 3 is a schematic diagram of an example of a liquid conduit (or a lower end portion of the conduit) and a liquid output component according to an embodiment of the present disclosure.

[0022] Figure 4 is a schematic diagram of a liquid dispensing system according to some embodiments of the present disclosure.

[0023] Figure 5 is a schematic diagram of an example of a system controller according to an embodiment of the present disclosure.

[0024] Figure 6 is a flowchart illustrating an example of a method of dispensing liquid according to an embodiment of the present disclosure.

[0025] Figure 7 is a flowchart illustrating another example of a method of dispensing liquid according to an embodiment of the present disclosure.

[0026] Unless specifically stated otherwise, all illustrations in the drawings are to be regarded as schematic diagrams. DETAILED DESCRIPTION

[0027] In this disclosure, all “aspects,” “examples,” “embodiments,” and “implementations” described are to be considered non-limiting and non-exclusive. Therefore, the fact that a particular “aspect,” “example,” “embodiment,” or “implementation” is explicitly described herein does not exclude other “aspects,” “examples,” “embodiments,” and “implementations” from the scope of this disclosure, even if not explicitly described. In this disclosure, the terms “aspects,” “examples,” “embodiments,” and “implementations” are used interchangeably and are considered to have interchangeable meanings.

[0028] In the present disclosure, when modifying a specified numerical value, the terms "substantially," "about," or "approximately" may be considered to include a value range of + / - 10% of the numerical value.

[0029] In this disclosure, the term "liquid" includes a single liquid phase component or a mixture or blend of two or more liquid phase components. Examples of liquids include, but are not limited to, solutions, suspensions, colloids, or emulsions. Liquids may contain or carry solid particles (e.g., inorganic particles, whole biological cells or dissolved cell components, etc.) and / or gas bubbles or vapor bubbles.

[0030] In this disclosure, the term "conduit" generally refers to any type of structure that encloses an internal space that defines a repeatable path for a fluid to flow from one point (e.g., the inlet of a conduit) to another point (e.g., the outlet of a conduit). A conduit generally includes one or more walls that define a pipe, tube, capillary, channel, manifold, chamber, etc. The cross-section (or cross-sectional flow area) of the inner hole or lumen of the conduit can have any shape, such as circular, elliptical, or polygonal. The conduit can be formed by any appropriate technology now known or later developed. The conduit can be formed from a variety of materials, such as fused quartz, glass, ceramic, polymer, and metal. In some embodiments, the material forming the conduit is optically transparent for purposes such as performing optical-based measurements or sample analysis, detecting or identifying substances flowing through the conduit, enabling a user to observe the flow and / or internal components in the conduit. Alternatively, the conduit can include an optically transparent window for this purpose.

[0031] In the present disclosure, the term "(bio)chemical compound" includes both chemical compounds and biological compounds.

[0032] The chemical compound can be, for example, a small molecule or a high molecular weight molecule (eg, a polymer, a carbohydrate, etc.).

[0033] Biological compounds can be, for example, biopolymers. Examples include, but are not limited to, nucleic acids (or polynucleotides). The term "nucleic acid" can refer to a biopolymer of any length consisting of nucleotides, such as more than about 2 bases, more than about 10 bases, more than about 100 bases, more than about 500 bases, more than 1000 bases, up to about 10,000 or more bases, such as deoxyribonucleotides or ribonucleotides, which can be produced enzymatically or synthetically and can hybridize with natural nucleic acids in a sequence-specific manner similar to two natural nucleic acids, such as can participate in Watson-Crick base pairing interactions. In addition to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), the term "nucleic acid" (or "polynucleotide") may include peptide nucleic acids (PNA), locked nucleic acids (LNA) and unstructured nucleic acids (UNA). The term "nucleic acid" can also be extended to non-natural nucleotides, such as dU and rT. Other examples include oligonucleotides (or "oligonucleotides"). The term "oligonucleotide" may refer to a biopolymer of nucleotides, which may be, for example, 10 to 300 or more nucleotides in length. Oligonucleotides may be synthetic or enzymatic. An oligonucleotide may contain ribonucleotide monomers (i.e., it may be an oligoribonucleotide) and / or deoxyribonucleotide monomers (i.e., it may be an oligodeoxyribonucleotide). An oligonucleotide may include modified nucleobases. Another example is a "gene," which may refer to a DNA segment (e.g., 10 2 -10 6base pairs (bp)). Another example is a "synthon," which may refer to a synthetic nucleic acid assembled in vitro from several shorter nucleic acids (e.g., oligonucleotides) according to a specific sequence or order. A synthon may include, for example, a chain assembled from 3 to 50 oligonucleotides. A synthon may be any sequence and, in some cases, may encode an amino acid sequence, i.e., a coding sequence. In other embodiments, a synthon may be a regulatory sequence, such as a promoter or enhancer. In certain cases, a synthon may encode a regulatory RNA. In some cases, a synthon may have a biological or structural function.

[0034] Figure 1 is a schematic diagram of an example of a liquid dispensing device 100 according to an embodiment. For description, Figure 1 A Cartesian coordinate system (XYZ) is included that is arbitrarily positioned relative to the diagram of liquid dispensing apparatus 100. The X-axis and Y-axis lie in a horizontal plane, which is considered to be any ground area or other surface (e.g., a bench, table, floor, etc.) supporting liquid dispensing apparatus 100 (or an apparatus of which it is a part). The Z-axis corresponds to the vertical direction. The dimensions of the X-axis, Y-axis, and Z-axis (e.g., dimensions associated with liquid dispensing apparatus 100 or any component thereof) are taken as length, depth, and height, respectively.

[0035] Liquid dispensing device 100 includes a housing 104 that surrounds the interior of the device. Housing 104 includes a top wall 108, a bottom wall 112, and one or more side walls 116 extending from top wall 108 to bottom wall 112. In an embodiment, top wall 108, bottom wall 112, and side walls 116 are adjacent to each other so as to completely surround the interior of the device except for the openings required for accommodating fluid components, electrical feedthroughs, etc. Liquid dispensing device 100 also includes a manifold (or common inlet conduit) 120 that is arranged inside the device. Manifold 120 includes a liquid inlet 124 that is arranged at one of top wall 108 (as shown) or side wall 116. Inlet 124 can be flush with or extend through the corresponding opening in top wall 108 (or side wall 116). Inlet 124 can include a suitable fluid connector, such as a Luer connector, a threaded connector, etc., or engage therewith to promote leak-free connection with a liquid input line (such as a pipeline). The liquid dispensing device 100 also includes a plurality of (outlet) conduits (or dispensing channels) 128 that are adjacent to the manifold 120 for fluid communication therewith. The conduits 128 terminate in respective liquid outlets 132 disposed at the bottom wall 112. The outlets 132 may be flush with or extend through respective openings in the bottom wall 112. With this configuration, the liquid dispensing device 100 defines a plurality of liquid flow paths that flow from the inlet 124 through the manifold 120 (the inlet 124 and the manifold 120 defining a common liquid inlet flow path) and into and through the conduits 128 to respective outlets 132 (the conduits 128 and the outlets 132 defining a plurality of liquid outlet flow paths branching from the common liquid inlet flow path). In the example shown, the conduits 128 (or at least the outlets 132) are arranged in a one-dimensional (1D) array along the X-axis or length of the liquid dispensing device 100. As used herein, the term "1D array" refers to a single row (or column) of conduits 128 (and corresponding outlets 132). A 1D array can follow a straight line along the X-axis or a curve in a net direction along the X-axis. Alternatively, the conduits 128 can be arranged in a two-dimensional (2D) array along the X-axis and the Y-axis. In other words, the conduits 128 can be arranged in one or more columns and one or more rows.

[0036] In a typical embodiment, the housing 104, manifold 120, and conduit 128 can be made of injection-molded plastic (e.g., an organic polymer or polymer blend). For example, the housing 104 can initially be provided in two halves that are adjoined (e.g., welded, glued, etc.) after the manifold 120, conduit 128, and any other internal components are joined. More generally, the aforementioned components can be made of plastic, metal, glass, or ceramic materials. Depending on their composition, the materials defining the inlet 124, conduit 128, and outlet 132 can be inherently chemically inert with respect to the liquid flowing through these components. Here, depending on the application of the liquid dispensing device 100, the term "chemically inert" can include the term "biocompatible" (or "bioinert") . Alternatively, as part of the manufacturing process, the inlet 124, conduit 128, and outlet 132 (or at least their inner surfaces) can be (bio)chemically passivated, for example, by applying a suitable coating (or film) or surface treatment / functionalization to render the conduit chemically inert and / or have a low absorption rate to the material. Coatings and surface treatments / functionalizations for such purposes are readily understood by those skilled in the art. For example, as will be appreciated by those skilled in the art, a "biocompatible" material, coating, or surface treatment / functionalization can effectively inhibit or prevent the migration of neutral molecules and / or ions from the inner surfaces of the inlet 124, conduit 128, and outlet 132 into the liquid flowing therethrough. Examples of chemically inert and / or biocompatible coatings can include, but are not limited to, members of the polyparaxylene family (e.g., polyparaxylene C), polyimides (PI), polyetherimides (PEI), members of the polyaryletherketone (PAEK) family (e.g., polyetherketone (PEK), polyetheretherketone (PEEK), polyetherketoneketone (PEKK), polyetheretherketoneketone (PEEKK), and polyetherketoneetherketoneketone (PEKEKK), and polymer blends containing one or more of the foregoing), and the like.

[0037] In a typical (but non-exclusive) embodiment, as shown, the manifold 120 is oriented horizontally, and the conduits 128 (or at least the outlets 132) are oriented vertically and parallel to each other. In other embodiments, the manifold and / or conduits 128 (and / or outlets 132) (all or part) can be oriented at an angle relative to the horizontal and vertical directions. In addition, the conduits 128 (or at least the outlets 132) are horizontally spaced apart from each other at a uniform distance (e.g., along the X-axis, or along a curve in the clear direction of the X-axis). In an embodiment, the spacing between the conduits 128 and / or outlets 132 (e.g., the horizontal distance between the center axes of the conduits 128 and / or outlets 132) is the same as the horizontal distance or spacing between the wells of the porous plate (or other type of container) that will receive the liquid dispensed volume (the liquid volume dispensed from the outlets 132). In other embodiments, one or more of the conduits 128 (or at least the outlets 132) can be unevenly spaced apart from adjacent conduits 128 (or outlets 132). In one example, the distance between the conduits 128 and / or the outlets 132 is in the range of 2 mm to 25 mm.

[0038] Figure 2 is a perspective view of an example of a multiwell plate 236. The multiwell plate 236 includes a support structure 240 and a two-dimensional (2D) array (i.e., rows and columns) of wells 244, which are typically integrally formed with the support structure 240. The multiwell plate 236 may also include a barcode 246 to facilitate identification and tracking of the multiwell plate 236. The 2D array may be a 2:3 rectangular array, such as Figure 2 96-well array (8 rows and 12 columns) shown. Figure 2Compared to the array shown, the number of holes in the 2D array can be more (e.g., 384, 1536, etc.) or less (e.g., 24, 54, etc.). As another option, the 2D array can be a square array, such as a 4x4 array of 16 holes or an 8x8 array of 64 holes, etc. In an embodiment, the multi-well plate 236 has a uniform spacing P between adjacent holes 244 in each row and each column of the array. For example, the spacing P can be taken as the distance between the centers of two adjacent holes 244 (i.e., the center-to-center distance). In an embodiment, the format of the multi-well plate 236, including the size and shape of the holes 244, is a standard format that conforms to a known standard, such as the multi-well plate standard of the American National Standards Institute / Society for Laboratory Automation and Screening (ANSI / SLAS) that is current at the time of filing this disclosure. For example, the spacing P can conform to the provisions of ANSI / SLAS 4-2004 (R2012): Microplates - Hole Positions. Thus, for an array of 96 wells 244, the pitch P may be 9.0 mm, for an array of 384 wells 244, the pitch P may be 4.5 mm, or for an array of 1536 wells 244, the pitch P may be 2.25 mm. When taking into account positional tolerances specified, for example, by ANSI / SLAS 4-2004 (e.g., + / - 0.7 mm for 96- and 384-well microplates, and + / - 0.5 mm for 1536-well microplates), the pitch P may be considered to be "substantially" equal to 9.0 mm, 4.5 mm, or 2.25 mm. As described above, the spacing between the conduits 128 and / or outlets 132 of the liquid dispensing device 100 should closely match the pitch P of the wells 244, particularly to avoid risks of cross-contamination, splashing, or spillage between adjacent wells 244.

[0039] The multiwell plate 236 is just one example of a group of liquid containers. In other embodiments, the wells 244 may be another type of liquid container and may be removable from the support structure 240. For example, the support structure 240 may be a rack, a frame, or the like, and the wells 244 may be vials, bottles, test tubes, or the like supported by the rack. These types of containers may be individually supported by the rack and, therefore, individually attachable to or detachable from the rack. Furthermore, such containers may be evenly spaced from one another in the manner just described with respect to the wells 244, or they may be unevenly spaced.

[0040] Return Reference Figure 1 In an embodiment, the housing 104 is shaped as a box having straight sides (i.e., a top wall 108, a bottom wall 112, and side walls 116). To minimize its overall footprint or form factor, the housing 104 can be sized just large enough to enclose the manifold 120, the conduit 132, and any other components disposed within the device. The minimal size of the housing 104 can also facilitate stacking multiple liquid dispensing devices 100 horizontally adjacent to each other, as shown below in conjunction with Figure 4As described above. If necessary, the minimized size can also facilitate regulating the temperature (and / or other operating conditions) inside the device. To this end, in the example shown, the housing 104 is shaped as a "thin" box (e.g., like a pizza box or a cereal box). In the context of the present disclosure, a "thin" box means that the maximum dimension of the housing 104 is its length (X direction) to accommodate the 1D (or 2D) array of conduits 132 and outlets 132, and the minimum dimension of the housing 104 is its depth (Y direction).

[0041] In the context of this disclosure, the terms "box" or "box-shaped" include a "generally" box-shaped housing 104. In other words, the sides of the housing 104 are not necessarily perfectly planar or have perfectly straight geometric shapes. In addition, features (e.g., wires, connectors, bosses, etc.) may protrude or be recessed from the outer surface of the sides of the housing 104. In all of these cases, the housing 104 is understood to be box-shaped.

[0042] The liquid dispensing device 100 further includes a plurality of valves 148, each disposed in the conduit 128, for individually controlling the flow of liquid through the conduit 128. The valves 148 can be configured to control the dispense volume (i.e., the total amount of liquid dispensed from the outlet 132 to the corresponding orifice 244 or other container), and the control can be based on flow time or flow rate.

[0043] In one embodiment, valve 148 is configured for on / off operation, for example, for switching between a (fully) open and a (fully) closed state. Generally, any type of on / off valve suitable for controlling liquid flow may be used, such as a solenoid valve. Valve 148 is individually controllable, i.e., controllable by a system controller (e.g., described below in conjunction with a controller) that is part of liquid dispensing device 100 or at least electrically connected to valve 148. Figure 4 and Figure 5The wells 244 are individually addressable (e.g., by the system controller 500 described herein). Thus, the corresponding wells 244 (in a given row or column aligned with the outlet 132) need not be filled with liquid at the same time. Instead, the wells 244 can be filled with liquid sequentially, or only a selected subset or group of wells 244 can be filled at a given time, while the remaining wells 244 are either unfilled or filled later. Furthermore, the amount of liquid dispensed into each well 244 is individually controlled by implementing a pulse / time approach. That is, the flow rate of liquid flowing into the conduit 128 (via the inlet 124 and the manifold 120) is maintained constant, and the amount of liquid dispensed into each well 244 is individually controlled by individually controlling the time period that the corresponding valve 148 is "open" or open (referred to herein as the "valve open duration"). In other words, by opening the corresponding valve 148 for different time periods (e.g., in the range of 10 ms to several hundred ms), different volumes (amounts or aliquots) of liquid can be dispensed into different wells 244. In such an embodiment, the flow of liquid into conduit 128 (flow rate, start and stop times of valve opening duration) can be controlled by a liquid moving device (not shown, but see FIG. 1 ) that delivers liquid to inlet 124. Figure 4 The dispense time of the outlet 132 (e.g., determined by a pulse / time method, etc.) may need to be controlled based on whether the orifice 244 moves relative to the outlet 132 during the dispense step and how the orifice 244 moves (e.g., stepwise or continuous).

[0044] Alternatively or additionally, the valve 148 can be configured to change (adjust) the liquid flow rate to values between and including fully open and fully closed states. In this case, if desired, the flow rate through the valve 148 can be individually controlled to enable different amounts of liquid to be dispensed into different holes 244. During such a dispensing operation, the operating time period of liquid flow through the conduit 128 can be maintained constant. To this end, in addition to the valve 148 configured for variable flow rate, one or more separate on / off valves (not separately shown) can be provided upstream of the variable flow rate valve 148 (e.g., in the conduit 128, manifold 120, or inlet 124). As an example, the valve 148 having a variable flow rate feature can be an active (i.e., controllable by a system controller) needle valve, in which the flow rate depends on the position of the needle relative to the valve seat, as will be understood by those skilled in the art. Such a needle valve may include an adjustable motion stop to enable the travel of the needle to be controlled / adjusted, for example, via a screw or spacer, such as an interchangeable spacer or a piezoelectric crystal that can be electronically adjusted to different sizes, thereby serving as a variable position stop for the needle's travel. Valve 148 may also be a proportional solenoid valve controlled by an analog signal. As another example, valve 148 may be a passive needle valve that is adjusted by screwing the valve into or out of its seat to vary the flow rate in the corresponding conduit 128. In this latter case, valve 148 itself may not be used to manage flow rate, but rather to act as a throttle for flow rate, and a separate valve (not separately shown) may be provided to manage the desired flow rate in the corresponding conduit 128. This latter case also allows calibration with a single flow rate sensor located, for example, at inlet 124, by opening one valve 148 at a time and then adjusting the valve 148 or generating the desired flow rate in the corresponding conduit 128. Another example of a variable flow rate valve is a peristaltic valve and actuator assembly. In all of these cases, the flow rate in the common inlet flow path through inlet 124 can be controlled by an upstream liquid moving device (not shown, but see Figure 4 The liquid moving device 410A-D) in the liquid moving device is changed.

[0045] Alternatively or additionally, the flow rate through the conduits 128 can be adjusted by providing different flow restrictions or resistances in the flow paths of the various conduits 128. As an example, the size of the orifice(s) of the outlet 132 can be adjusted, for example, between orifice filling operations. This can be achieved, for example, by configuring the outlet 132 to receive replaceable / interchangeable outlet components (e.g., nozzles, needles, pipette tips, etc.) having different orifice sizes (selectable by the user), thereby allowing the dispensing rate through the outlet 132 to be substantially varied when desired.

[0046] The liquid dispensing apparatus 100 may also include one or more flow rate sensors 152. For example, the liquid dispensing apparatus 100 may include multiple flow rate sensors 152, each disposed in (or on) the conduit 128, to significantly enhance control of the flow of liquid through the conduit 128, thereby enhancing control and accuracy of the total dispense volume, i.e., the total volume (amount) of liquid dispensed from each of the active outlets 132 (i.e., the outlets 132 used during a given dispensing operation) into the underlying container. As desired, the flow rate sensor 152 may be located in the conduit 128 upstream or downstream of the valve 148 (as shown), and / or in the manifold 120 or inlet 124. The flow rate sensor 152 may be positioned to communicate with a system controller (e.g., Figure 4 and Figure 5 The system controller 500 (shown in FIG. 1 ) communicates with the flow rate sensor 152 to provide an active feedback loop (i.e., closed-loop control) in each conduit 128. The total dispensed volume from each outlet 132 can be set or programmed, for example, by a user or the system controller (e.g., based on feedback data received from the flow rate sensor 152, data retrieved from a lookup table stored in memory, and / or data or instructions received from software). Examples of the type of flow rate sensor 152 used include, but are not limited to, ultrasonic-based sensors, thermal-based sensors, and capacitive sensors.

[0047] Feedback measurements from the flow rate sensor 152 can be used to make one or more types of adjustments to the liquid flow-related operating parameters of the liquid dispensing device 100, depending on whether the dispense volume is determined by the valve opening duration in the case of a constant flow rate, or by the flow rate in the case of a variable flow rate valve 148 or a variable flow rate liquid flow device upstream of the valve 148. The flow rate sensor feedback can be used to make adjustments in real time (dynamically) during a given dispensing operation. For example, the flow rate sensor 152 can be used to determine whether the flow rate in each conduit 128 is correct (e.g., whether the flow rate deviates from a preset value (set point) or other expected value, or whether it exceeds an acceptable tolerance range for the flow rate value). For any conduit 128, if the actual (measured) flow rate is determined to be incorrect, appropriate adjustments can be made (e.g., to the valve opening duration or the flow rate itself) as needed to ensure that the prescribed dispense volume for each conduit 128 (or at least its outlet 132) is achieved.

[0048] Similarly, assuming the flow rate in all operating conduits 128 is the same (e.g., according to a preset flow rate), the flow rates in the various conduits 128 can be compared to determine if the flow rate in one or more conduits 128 is different from the flow rate in the other conduits 128 and / or different from the expected or (pre)set flow rate. If necessary, the flow rate in one or more conduits 128 can be adjusted to ensure that the conduit 128 (or those conduits 128) dispenses the correct volume of liquid.

[0049] Flow rate sensor feedback can also be used to adjust the nature of corrections, compensations, or calibrations that improve the accuracy of subsequent dispensing operations. For example, during or after a test run in preparation for an actual dispensing operation, or during or after a given dispensing operation in preparation for the next dispensing operation, adjustments can be made based on measured flow rate data (e.g., to correct or compensate for inaccuracies determined in one or more conduits 128 (or outlets 132)). As an example of a condition that may require correction, the flow rate through a given conduit 128 may vary based on the number of other conduits 128 in operation (i.e., the number of valves 148 open in the other conduits 128), based on different back pressures experienced by the conduits 128, or other factors, and the magnitude of the variation may depend on which conduit 128 is being evaluated for such conditions. Furthermore, the flow rate may vary for each conduit 128 (or at least its outlet 132) regardless of how many or which conduits 128 are in operation simultaneously.

[0050] The flow rate sensor 152 may also be used to verify that the valve actuation is functioning properly, such as by detecting a malfunctioning (eg, stuck or leaking) valve 148 , or for detecting a clogged conduit 128 or outlet 132 .

[0051] Feedback from the flow rate sensor 152 can also be used in a test run of the liquid dispensing apparatus 100 to determine whether the raw flow rate measurement data output from the flow rate sensor is accurate or inaccurate (due to a number of factors associated with the flow rate sensor 152 itself, such as noise, drift, structural wear, fouling, etc.). If the raw flow rate measurement data is determined to be inaccurate, the system controller can make corrections to the raw data (e.g., calculated offset values, scaling factors, etc.).

[0052] In some embodiments, a dispensed volume of liquid container (e.g., as described above with reference to Figure 2 The holes of the porous plate) are movable relative to the liquid distribution device 100 and thus relative to the outlet 132 (for example, see below for Figure 4As an example, the liquid container can be moved in a stepwise (indexed) manner (e.g., moving, receiving a dispensed volume in a column or row, moving, receiving an additional dispensed volume in the next column or row), etc.). In this case, the timing of the iterative movement of the liquid container can be coordinated or synchronized with the timing of the dispense (e.g., can be controlled by valve 148, which can be assisted by feedback from flow rate sensor 152), and valve / flow rate control (e.g., adjustment, calibration, etc.) can be performed as described above and elsewhere in this document. As another example, the liquid container can be moved in a continuous manner. In this case, the dispense time can be coordinated or synchronized with the position of the liquid container relative to the outlet 132. For example, the operation of valve 148 can be controlled (e.g., the start and stop time of the valve opening condition, or the on / off state of valve 148, which can be assisted by feedback from flow rate sensor 152) to adjust the flow rate between outlets 132 as needed to ensure that the dispense time only occurs within the time window when the outlet 132 is aligned with the liquid container, thereby ensuring the correct total dispense volume in each liquid container and avoiding spillage or splashing of the dispensed liquid.

[0053] In another embodiment, a single flow rate sensor 152 can be located upstream of the conduits 128, such as at the inlet 124 or manifold 120, to measure the flow rate of the common inlet flow. With this configuration, the flow rate in a single conduit 128 can be measured while the other conduits 128 (or a subset of the other conduits 128) are closed (deactivated). This flow rate measurement can be performed for each conduit 128 provided.

[0054] Liquid dispensing device 100 may also include a temperature control device 156 configured to heat and / or cool the liquid in conduits 128. Like other active components of liquid dispensing device 100, temperature control device 156 may be in electrical communication with the system controller, thereby being controllable by the system controller. In one embodiment, temperature control device 156 is or includes a heating device. The heating device may include one or more heating elements disposed within the device, configured (e.g., sized, shaped, positioned) to transfer thermal energy to the liquid in conduits 128 via thermal conduction and / or thermal convection. By way of example, the heating element(s) may be mounted to the interior surface of one or more of top wall 108, bottom wall 112, and side walls 116. Alternatively, each heating element may be mounted directly on the exterior surface of conduits 128. In the illustrated example, a strip-shaped heating element is positioned along the length (X-axis) of the interior surface of at least one side wall 116, ensuring (substantially) uniform thermal energy transfer to each conduit 128. Also in the illustrated example, the heating element is positioned near outlet 132, enhancing the ability to regulate the liquid temperature at the point of dispensing. This configuration may be advantageous, for example, to ensure that the concentrated solution does not crystallize, thereby preventing undesirable clogging of the outlet 132, and / or to control the viscosity of the liquid, etc. Generally, as will be appreciated by those skilled in the art, any type of heating element may be used. As a non-exclusive example, the heating element may be a resistive (Joule or Ohm) heating element.

[0055] Additionally or alternatively, the temperature control device 156 is or includes a cooling device configured to cool the liquid in the conduit 128. A non-exclusive example of a cooling device is a thermoelectric cooling device, such as a Peltier cooling device or the like.

[0056] The temperature control device 156 may also include one or more temperature sensors configured to measure the temperature of the liquid in the conduit 128. Figure 1 , a temperature control device 156 is used to schematically represent such a temperature sensor and a heating and / or cooling element. The temperature sensor can also be placed in communication with the system controller to provide closed-loop control of the heating and / or cooling element. In this way, the liquid temperature can be maintained within a desired range, which can be a narrow range and can be adjusted for different dispensing operations based on the composition of the dispensed liquid. Generally, as will be appreciated by those skilled in the art, any type of temperature sensor can be used. Examples of temperature sensors include, but are not limited to, resistance temperature detectors (RTDs), thermocouples, thermistors, and infrared (IR) based sensors.

[0057] The liquid dispensing device 100 may also include one or more locally located electronically based control circuit modules 160 that communicate with the active (electronically controlled) components (e.g., valve 148, flow rate sensor 152, temperature control device 156) provided with the liquid dispensing device 100 via a suitable communication link 164, in particular to provide closed-loop control of the various liquid channels described herein. The control circuit modules 160 may be locally located, i.e., they are disposed at the liquid dispensing device 100, such as on or in the housing 104. As will be appreciated by those skilled in the art, the control circuit modules 160 may include any combination of hardware or firmware components (e.g., microelectronic chips, integrated circuits (ICs), and solid-state circuit components (e.g., resistors, capacitors, inductors, etc.) mounted on a rigid circuit board or flexible circuit substrate) suitable for implementing control and monitoring of the active components. The control circuit modules 60 may be configured to implement all system control functions required to operate the liquid dispensing device 100 and / or may communicate with a more remotely located system controller that is part of a larger system or device that includes the liquid dispensing device. The communication link 164 can be a rigid or flexible circuit whose wiring is configured as a bus, ribbon, cable, etc. Alternatively, one or more communication links 164 can be wireless (e.g., a link involving the transmission (transmission and / or reception) of radio frequency (RF) signals propagating through the air). Generally, any electrical interconnection technology can be used. One or more electrical connectors or feedthroughs 168 can be mounted at one or more corresponding openings in the housing 104 (e.g., the top wall 108 or the side wall 116 as shown) to provide communication with electrical components disposed within the device (e.g., power supply, data transmission, control signal transmission, etc.). Alternatively or additionally, the control circuit module 160 can be or include an RF transceiver component that serves as a wireless interface for sending signals to and / or receiving signals from a remote server or network.

[0058] As will be apparent from this description, the primary function of the liquid dispensing device 100 is to take a single liquid input stream and distribute it to a plurality of separate liquid channels (embodied as unique liquid output circuits or conduits 128), wherein the conditions of each output stream can be uniquely controlled (e.g., with respect to on / off state, dispensed volume, flow rate, temperature, etc.). Compared to previously known devices (such as inkjet printer heads and pipette heads, etc.), the liquid dispensing device 100 can be adapted to dispense a wide range of different liquids in significantly larger volumes and is much less sensitive to varying conditions such as viscosity. The mechanical layout of the liquid dispensing device 100 allows for integration into a larger (typically automated) system or apparatus, which is typically used as a filling device for well plates or other containers. The liquid dispensing device 100 is capable of performing a wide range of tasks, either alone or in conjunction with a larger system of which it is part, ranging from simply adding individual liquids to wells to more complex procedures involving, for example, mixing, dilution, buffering, solvation, emulsification, precipitation, gelation, other types of liquid conditioning, (bio)chemical reactions, (bio)chemical synthesis or assembly, lysis, chemical or enzymatic cleavage, hybridization, denaturation, labeling (e.g., with dyes, fluorophores, etc.), distillation, fractionation, filtration, analytical separation and / or collection of sample components, purification, detection / measurement of analytes, etc. Another application is the preparation of well plates for cell culture with varying amounts of material in each designed experiment.

[0059] One specific application of the liquid dispensing device 100 is microscale DNA / RNA synthesis. In current state-of-the-art synthesis tools, the mechanical complexity and opportunities for leakage are substantial and substantial. The liquid dispensing device 100 can be used for oligonucleotide production related to DNA / RNA synthesis, but at a scale sufficient to synthesize sufficient amounts of DNA / RNA to directly provide for applications such as CRISPR / CAS9 (clustered regularly interspaced short palindromic repeats / CRISPR-associated protein 9) gene editing.

[0060] In various embodiments, a liquid dispensing apparatus 100 comprising a 1D or 2D array of conduits 128 and corresponding outlets 132 can be operated in conjunction with a movable multiwell plate or other type of container array (e.g., movable through the underside of the liquid dispensing apparatus 100) to deliver a (possibly unique) volume of liquid to one or more selected columns of wells in the multiwell plate (e.g., Figure 2 As many as twelve eight-column wells of the multiwell plate 236 shown in ; see also Figure 4 In some embodiments, a set of liquid dispensing devices 100 (such as Figure 1The liquid dispensing devices 100 shown in the figure, etc.) can be stacked together (e.g., horizontally or side by side) to provide a greater number of liquid dispensing points, from which liquid volumes can be delivered simultaneously or sequentially (in terms of a single well or a predetermined group of wells) as needed, and each liquid dispensing device 100 (or one or more liquid dispensing devices 100) supplies different liquids as needed. In this way, a variety of procedures can be implemented, such as adding two or more different liquids from two or more corresponding liquid dispensing devices 100 to the same well or other container (e.g., dispensing a sample solution from one liquid dispensing device 100 and then adding a reagent to the sample solution in the same well or other container from another liquid dispensing device 100, etc.). Such groups or stacks of liquid dispensing devices 100 can also work in conjunction with a movable multi-well plate or other type of container array. For each liquid dispensing device 100, the delivery of a single type of liquid and the physical spacing between the liquid dispensing points prevent cross-contamination between the liquid channels of the liquid dispensing device 100.

[0061] In some embodiments, the liquid dispensing device 100 (or stack of liquid dispensing devices 100) remains stationary while the multiwell plate (or other type of container array) can be moved relative to the liquid dispensing device 100. By eliminating the components required to drive and control the movement of the liquid dispensing device 100 itself, the liquid dispensing device 100 is simpler and more reliable than known methods (such as robotically movable inkjet printheads and pipetting heads, etc.). In addition, the plate filling productivity can be very fast compared to known methods (such as pipetting from one container to another, etc.). By eliminating the pipette tip filling and moving process, the plate filling productivity of laboratory automation tools can be greatly improved. In addition, the need for frequent replacement of pipette tips is eliminated, thereby reducing waste.

[0062] As an example, the inner diameter of the conduit 128 is in the range of 500 μm to 5000 μm. The inner diameter of the outlet 132 can be (substantially) the same as or smaller than the inner diameter of the conduit 128. The flow rate through the conduit 128 can be in the range of 5 mL / min to 500 mL / min. The volume of liquid dispensed by each conduit 128 (during one iteration) can be in the range of 10 μL to 1000 μL. More generally, the volume of liquid dispensed is effectively limited only by the volume (size) of the orifice 244 or other container used.

[0063] Figure 3FIG2 is a schematic diagram of an example of one of the conduits 128 (or the lower end portion of the conduit 128) and a liquid output component 372 according to an embodiment. The liquid output component 372 is attached to the conduit 128 at the outlet 132. To this end, the outlet 132 may include an engagement portion 376 that serves as a fitting or adapter, i.e., configured to attach to or mate with a complementary engagement portion 380 of the output component 372. Alternatively, as shown, a separate fitting or adapter 384 may be provided to fluidically interconnect the outlet 132 and the output component 372. In this case, the fitting 384 may include an engagement portion 388 that is configured to attach to or mate with the complementary engagement portion 376 of the outlet 132, and another engagement portion 392 that is configured to attach to or mate with the complementary engagement portion 380 of the output component 372. The engagement portions 376, 380, 388, 392 may have any configuration suitable for creating a robust fluid coupling, such as screw-type threads, Luer-type fittings, etc. The type of output component 372 coupled to the outlet 132 of the conduit 208 depends on the embodiment. Examples of the output component 372 include, but are not limited to, a pipette tip, a needle (possibly configured to pierce a septum), a nozzle, or a component having an orifice of a different size (e.g., inner diameter) than the outlet 132. Providing a fitting or adapter, either integral with the outlet 132 or attached to the outlet 132, enables different types and / or sizes of output components 372 to be used with each conduit 128, thereby increasing the flexibility of use of the liquid dispensing device 100. By way of example, different output components 372 can be used to provide different flow rates at the point of dispensing, or to accommodate different sizes and / or types of orifices or other containers.

[0064] Figure 4 is a schematic diagram of a liquid dispensing system 400 according to some embodiments. The liquid dispensing system 400 includes one or more liquid dispensing devices, each of which can be configured as disclosed herein, for example, as described above and Figure 1 (or another Figure 3 ) shown in the liquid dispensing device 100. For example, Figure 4 Four liquid dispensing devices 100A, 100B, 100C, and 100D are shown, but fewer or more than four may be provided. Each liquid dispensing device 100A-D includes a respective liquid inlet 124A-D, a set (e.g., eight, see Figure 1 ) Liquid outlet 132A-D and above combined Figure 1 (or another Figure 3 ) other components described above. The liquid distribution system 400 may also include one or more porous plates 236, as described above in conjunction with Figure 2Thus, in the example shown, the porous plate 236 has a 2D array of holes 244A, 244B, 244C, 244D, ..., and 244L. Specifically, Figure 4 , 12 columns of wells (244A, 244B, 244C, 244D, ..., and 244L) are spaced apart along the X-axis, and 8 rows of wells are spaced apart along the Y-axis (orthogonal to the plane of the drawing). The liquid dispensing system 400 may include an optical reader (not shown) for reading any barcode 246 ( Figure 2 ).

[0065] In an embodiment, as shown, the liquid dispensing devices 100A-D are stacked or arranged horizontally in a linear (1D) array, resulting in the outlets 132A-D being arranged in a 2D array. In an embodiment, the liquid dispensing devices 100A-D are stacked in a tightly packed configuration. Thus, except for one set of outlets 132A-D of each liquid dispensing device 100A-D in a horizontal direction (e.g., Figure 4 In addition to being evenly spaced from one another along the Y-axis (optionally), each set of outlets 132A-D of each liquid dispensing device 100A-D may also be spaced apart from each other along the Y-axis (optionally), each set of outlets 132A-D of each liquid dispensing device 100A-D may also be spaced apart from each other along the Y-axis (optionally). Figure 4 The corresponding adjacent outlets 132A-D are evenly spaced apart. Figure 2 As described above, the horizontal spacing between adjacent outlets 132A-D along two horizontal directions (X-axis and Y-axis) can be (substantially) equal to the spacing P of the holes 244A-L of the 2D array of the porous plate 236. This configuration facilitates alignment of the selected outlet group 132A-D (i.e., the outlets 132A-D of the selected liquid dispensing device 100A-D) with the selected hole group 244A-L. The liquid dispensing system 400 may include a fixture (e.g., a frame, a container, etc.; not specifically shown) on which the liquid dispensing devices 100A-D are mounted. The fixture can be configured to organize the liquid dispensing devices 100A-D into a linear array so that the outlets 132A-D are aligned in the direction of travel of the porous plate. To this end, the housing 104 ( Figure 1 ) can provide consistent spacing between the outlets 132A-D and at least one side of the housing 104.

[0066] In another embodiment, the liquid dispensing system 400 may include twelve liquid dispensing devices 100, such that all of the wells 244A-L of the 2D array can be aligned with the corresponding outlets 132 of the twelve liquid dispensing devices 100 at the same time. More generally, the number of liquid dispensing devices 100 provided can match the number of rows or columns of the provided container array. Furthermore, as previously described, each liquid dispensing device 100A-D can itself include the outlets 132 of the 2D array, in which case only one liquid dispensing device 100A-D, or only a few liquid dispensing devices 100A-D, may be required to supply liquid to the wells 244A-L during a given operation.

[0067] The liquid dispensing system 400 also includes one or more liquid reservoirs (e.g., bottles, vials, bags, etc.) and one or more liquid moving devices in fluid communication with the liquid inlets 124A-D via suitable liquid lines (e.g., conduits, pipes, etc.). In this example, the liquid dispensing system 400 includes four liquid reservoirs 406A-D and four liquid moving devices (or liquid flow devices) 410A-D configured to flow liquid from the respective liquid reservoirs 406A-D to the respective liquid inlets 124A-D. Fewer or more than four liquid reservoirs 406A-D and four liquid moving devices 410A-D may be provided.

[0068] Depending on the embodiment or application, different reservoirs 406A-D may contain the same liquid or different liquids. For example, one reservoir 406A-D may supply a solution containing a sample to be measured or analyzed, while another reservoir 406A-D may supply a different sample solution, or a reagent (e.g., for reacting with, deprotecting, cleaving, hybridizing, denaturing, or synthesizing a (bio)chemical compound), a buffer, a diluent, a solvent, an emulsifier, a label or other type of additive, or two different reagents, a cell culture medium, etc.

[0069] In general, the liquid moving devices 410A-D may be devices configured to establish a flow of liquid from the reservoirs 406A-D to the respective inlets 124A-D (i.e., to generate a force effective to move the liquid through the appropriate liquid lines). Figure 4, liquid moving devices 410A-D are depicted as being separate from reservoirs 406A-D, but depending on the embodiment, liquid moving devices 410A-D may be located at or integrated with reservoirs 406A-D. Additionally, depending on the embodiment, liquid moving devices 410A-D may be positioned upstream of reservoirs 406A-B rather than downstream. Furthermore, liquid moving devices 410A-D and / or reservoirs 406A-D may be positioned within the device of the corresponding liquid dispensing device 100A-D. As an example, liquid moving devices 410A-D may be separate pumps (or pumping units) or separate liquid channels of a single pump. Various types of pumps may be used, such as reciprocating pumps (e.g., syringe or piston pumps), impeller pumps, peristaltic pumps, etc. Liquid moving devices 410A-D may be configured to provide a variable liquid flow rate or fluid pressure that can be set / adjusted by a user, a system controller, or software. Additionally or alternatively, the liquid moving devices 410A-D can be configured to provide a constant liquid flow rate or fluid pressure that is selectively varied by a flow regulating device external to or internal to the liquid dispensing device 100A-D. As another example, the liquid moving devices 410A-D can be configured as a controllable pressure source (with or without a moving pumping element) that applies fluid pressure (e.g., using a suitable gas such as air, helium, nitrogen, argon, etc.) to the reservoirs 406A-D (e.g., to a movable boundary such as a diaphragm, etc.) or to a liquid line connecting the reservoirs 406A-D to the internal flow path of the liquid dispensing device 100A-D. In this case, the internal pressures of the reservoirs 406A-D can be individually controlled to manage flow rates, for example, to ensure consistent dispensing times between different liquid dispensing devices 100A-D. In a similar example, the reservoirs 406A-D can be configured to move liquid in response to a gas overpressure generated in the reservoirs 406A-D by the liquid moving devices 410A-D as a pressure source. As another example, the liquid moving devices 410 can be implemented by an arrangement of the reservoirs 406A-B and associated liquid outlet lines in communication with the inlets 124A-D of the liquid dispensing devices 100A-D that enables gravity to act as a motive force for delivering liquid, as in the manner of an IV bag.

[0070] The liquid dispensing system 400 also includes a hardware transport system (or subsystem) configured to move one or more components of the liquid dispensing system 400 relative to other components (which themselves may be movable or stationary). In this example, the hardware transport system is or includes a container (e.g., plate) transport system (or subsystem) 414 that is configured to move one or more multiwell plates 236 (or other types of liquid containers) relative to the liquid dispensing apparatus 100A-D. Figure 4, the container transport system 414 is depicted by a movable stage 418 that is mechanically coupled to a drive or robot 422 via a drive linkage 426 (e.g., a belt and pulley, a chain and gears, a screw and worm gear, etc.). The movable stage 418 is configured to securely support one or more porous plates 236 during movement. The movable stage 418 can be configured as a conveyor that is driven to move the porous plates 236 along the X-axis in a step-by-step or continuous manner (i.e., similar to an assembly line configuration). More generally, the movable stage 418 can represent one or more stages / carriages that can be moved along one or more axes (e.g., an X-axis, a Y-axis, and a Z-axis) as needed to move the porous plates 236 to and from the liquid dispensing apparatus 100A-D, including moving them into proper fluid alignment with selected outlets 132A-132D of the liquid dispensing apparatus 100A-D. As used herein, the term "fluid alignment" refers to the position of a given aperture 244A-L relative to a corresponding outlet 132A-132D (or vice versa) at which a desired volume of liquid can be successfully dispensed from the outlet 132A-132D into the aperture 244A-L without loss (or any noticeable loss) of the dispensed liquid (e.g., due to spillage or splashing). Thus, in a typical example, a given aperture 244A-L is fluidly aligned with a corresponding outlet 132A-132D when the aperture 244A-L is directly below (and typically very close to) the outlet 132A-132D.

[0071] The platform 418, robot 422 and drive link 426 schematically represent any combination of components that can be used to move the multiwell plate 236 (or other type of container support) along a desired number of different axes (in a desired number of different directions) in an automatic (robotic) manner, such as those skilled in the art will appreciate, typically provided in laboratory automation tools. Thus, for example, the platform 418 can be, for example, a carriage that translates along a certain axis on a linear guide, which can be supported on another platform (or carriage), which translates along another axis on another linear guide, which can in turn be supported on yet another platform (or carriage), which translates along yet another axis on yet another linear guide. The robot 442 includes one or more motors (e.g., precision bidirectional stepper motors) that drive the platform 418, local motion control circuitry as needed, and possible position sensors (e.g., encoders) that track the movement or position of the platform 418. The drive linkage 426 includes components (eg, screws, belts, chains, etc.) that mechanically couple the motion generated by the motors of the robot 442 to the motion of the stage 418 .

[0072] In particular, as described above, the stage 418 can be moved to one or more positions in which selected wells 244A-L are fluidically aligned with the outlets 132A-132D of the liquid dispensing devices 100A-D. In the example shown, the first four columns of wells 244A-D are aligned with the outlets 132A-132D of the 2D array. In some embodiments, two or more reservoirs 406A-D contain different liquids, and thus two or more liquid dispensing devices 100A-D are configured to deliver different liquids to the selected wells 244A-L. In other embodiments, the reservoirs 406A-D contain the same liquid, and the multiple liquid dispensing devices 100A-D can be primarily used for high-throughput filling operations.

[0073] As an example of a method or procedure, the liquid dispensing apparatus 100A-D can deliver (simultaneously or sequentially) controlled volumes of the same or different liquids to two or more columns of the first four columns of wells 244A-D. If the total number of outlets 132A-132D is less than the total number of wells 244A-L (e.g., if the total number of liquid dispensing apparatuses 100A-D is less than the total number of wells 244A-L), the dispensing process can be repeated in conjunction with the translation stage 418 / multiwell plate 236. For example, in the illustrated embodiment where four liquid dispensing apparatuses 100A-D are provided, the stage 418 / multiwell plate 236 can first be moved to a first position in which the first four columns of wells 244A-D are fluidically aligned with the corresponding outlets 132A-132D of the liquid dispensing apparatuses 100A-D. The desired volume of liquid is then dispensed into the selected wells 244A-D. Next, the stage 418 / multiwell plate 236 can be moved to a second position in which the next four columns of wells (i.e., 244E-H, Figure 4 The desired volume of liquid is then dispensed into the selected wells (244E-H). Next, the stage 418 / multiwell plate 236 can be moved to a third position where the next four columns of wells (i.e., 244I-K, Figure 4 132D. The desired volume of liquid is then dispensed into the selected wells (244I-L). In this way, all wells 244A-L (or all selected wells in the entire array of wells 244A-L) can be filled with liquid, and up to four different liquids can be delivered from the corresponding liquid dispensing apparatus 100A-D, if desired. More generally, any number of different liquids can be dispensed into the wells 244A-L, depending on the number of liquid dispensing apparatuses 100A-D provided.

[0074] As another example, two or more of the liquid dispensing devices 100A-D can (sequentially) deliver controlled volumes of different liquids to wells in the same column (e.g., one of the wells 244A, 244B, 244C, or 244D). In this way, two or more liquids can be mixed in the same well for a specific application task (e.g., cell culture, mixing, dilution, reaction, labeling, pH adjustment, synthesis, etc.). This combined operation involves moving the multi-well plate 236 (e.g., along the X-axis, such as Figure 4 The stage 418 (as indicated by the double-headed arrows in FIG. 4 ) can be moved into alignment with two or more sets of outlets 132A-132D of the liquid dispensing apparatuses 100A-D to enable dispensing of two or more liquids in two or more corresponding steps. For example, the stage 418 can be operated to move the first array of wells 244A into alignment with the outlets 132A of the first liquid dispensing apparatus 100A. The first liquid dispensing apparatus 100A can then be operated to deliver a controlled volume of the first liquid from the first reservoir 406A into the first array of wells 244A. The stage 418 can then be operated to move the first array of wells 244A into alignment with the outlets 132B of the second liquid dispensing apparatus 100B. The second liquid dispensing apparatus 100B can then be operated to deliver a controlled volume of the second liquid from the second reservoir 406B into the first array of wells 244A, thereby mixing the first and second liquids in the first array of wells 244A.

[0075] In all of the above examples, the process can be repeated for other columns of wells 244A-L, depending on the method being implemented, by moving the multi-well plate 236 in a stepwise (indexed movement or start / stop) or continuous manner as needed in coordination with the components responsible for controlling the dispensing of liquid from the outlets 132A-132D. In all of the above examples, if desired, each liquid dispensing device 100A-D can be controlled or programmed to dispense different volumes of liquid (or even zero volume of liquid) from its different outlets 132A-132D into corresponding wells of a given column of wells 244A, 244B, 244C, or 244D, as described above in conjunction with Figure 1 As stated.

[0076] The liquid dispensing system 400 also includes a system controller (or controller or computing device) 500. The system controller 500 may schematically represent one or more modules (or units or components) configured to control, monitor and / or time various functional aspects of the liquid dispensing system 400, such as, for example, liquid input flow to and output flow from the liquid dispensing apparatuses 100A-D, temperatures in the liquid dispensing apparatuses 100A-D, tracking and movement of the stage 418 and plate 236 or other containers supported thereon, preparation, conditioning, processing, measurement and / or analysis of liquid before and / or after dispensing, addressing, identification, etc. For all of these purposes, the system controller 500 may communicate with one or more components of the liquid dispensing system 400, either wired or wirelessly (e.g., Figure 4 ), and may include any suitable combination of hardware, firmware, software, etc. (including one or more electronically based processors and memories), as understood by those skilled in the art. For example, the system controller 500 may include a non-transitory (or tangible) computer-readable medium including non-transitory instructions for executing any of the methods disclosed herein. Figure 5 Another example of the system controller 500 is described.

[0077] Depending on the embodiment, the liquid dispensing system 400 may also be part of (or at least operate in conjunction with) a larger system that includes various other components necessary for proper operation that are not specifically shown but would be understood by those skilled in the art, such as in the fields of high-throughput liquid handling and sample detection or analysis. Examples of such other components may include, but are not limited to, a humidity control device configured to minimize evaporation of liquid from within the liquid dispensing device 100A-D; one or more analytical instruments for analyzing the liquid before or after dispensing the liquid into the container array or plate 236 (e.g., a solid phase extraction (SPE) instrument, a liquid chromatography (LC) instrument, an electrophoresis instrument, a mass spectrometer (MS), an ion mobility spectrometer (IMS), a UV / visible / infrared spectrometer, an atomic emission spectrometer (AES) or an optical emission spectrometer (OES) instrument, a microscope, or other measurement or imaging instrument based on visible light, fluorescence, phosphorescence, luminescence, or absorbance); a container (or plate) handling system that may, for example, include a one or more devices for gripping / manipulating containers or plates (e.g., robotic gripper elements or other end effectors) to load them onto the stage 418 (e.g., from storage racks, coolers, incubators, etc.) and to remove them from the stage 418 (e.g., for transport to an analytical instrument, a reaction or synthesis station, etc.); a position sensor (e.g., an optical encoder, a relay switch, etc.) for detecting the position of a container or plate and / or its presence at a particular location; a liquid sensor for detecting the presence of liquid in a well 244 or other container and / or measuring the volume of liquid therein; an optical reader for reading a bar code or other marking that uniquely identifies the container, container holder, or multiwell plate 236 being used; and the like.

[0078] Figure 5 is a schematic diagram of an example of a system controller 500 according to an embodiment. As described above, the system controller 500 can schematically represent one or more modules, control units, components, etc., which are configured to control, monitor, analyze and / or time the operation of various devices or components that may be provided in the liquid dispensing system 400 (or, additionally, a larger system of which the liquid dispensing system 400 is a part or with which the liquid dispensing system 400 operates), as well as control or perform one or more steps of any method disclosed herein (e.g., steps related to flow measurement and control, etc.). In addition Figure 1 and Figure 4In addition to those shown, these devices may also include, for example, sample preparation / conditioning devices, analytical instruments, voltage sources, timing controllers, clocks, frequency / waveform generators, processors, logic circuits, memories, databases, etc. One or more modules of the system controller 500 may be or be embodied in, for example, a computer workstation, a desktop computer, a laptop computer, a portable computer, a tablet computer, a handheld computer, a mobile computing device, a personal digital assistant (PDA), a smartphone, etc. As will be understood by those skilled in the art, one or more modules of the system controller 500 may communicate with one or more other modules via one or more buses or other types of communication lines or wireless links.

[0079] In the illustrated embodiment, the system controller 500 includes one or more electronic-based processors 502, which can represent a main electronic processor that provides overall control, as well as one or more electronic processors configured for dedicated control operations or specific signal processing tasks (e.g., a graphics processing unit or GPU, a digital signal processor or DSP, an application-specific integrated circuit or ASIC, a field-programmable gate array or FPGA, etc.). The system controller 500 also includes one or more memories 504 (volatile and / or non-volatile types, such as RAM and / or ROM) for storing data and / or software. For example, the stored data can be organized in one or more databases or lookup tables. The system controller 500 can also include one or more device drivers 506 for controlling one or more types of user interface devices and providing an interface between the user interface devices and components of the system controller 500 that communicate with the user interface devices. Such user interface devices can include user input devices 508 (e.g., a keyboard, keypad, touch screen, mouse, joystick, trackball, etc.) and user output devices 510 (e.g., a display screen, printer, visual indicators or alarms, audible indicators or alarms, etc.). In various implementations, the system controller 500 may be considered to include, or at least be in communication with, one or more of the user input device 508 and / or the user output device 510 .

[0080] The system controller 500 may also include one or more types of computer programs or software 512 contained in memory and / or on one or more types of non-transitory (or tangible) computer-readable media 514. The computer-readable media 514 may also represent one or more devices of the system controller 500 that are configured to receive and read (and optionally write to) the computer-readable media 514. The computer programs or software 512 may include non-transitory instructions (e.g., logic instructions) for controlling or performing various operations of the liquid dispensing system 400 (or additionally, a larger system of which the liquid dispensing system 400 is a part or operates with), such as flow measurement and control, etc. The computer programs or software 512 may include system software and application software. The system software may include an operating system (e.g., Microsoft Windows) for controlling and managing various functions of the system controller 500, including the interaction between hardware and application software. Operating system). Specifically, the operating system can provide a graphical user interface (GUI) that can be displayed via user output device 510, and the user can interact with the GUI by using user input device 508. The application software can include software configured to control or execute various operations of the liquid dispensing system 400 and / or some or all steps of any method disclosed herein.

[0081] The system controller 500 may also include a controller configured to control the liquid moving devices 410A-D ( Figure 4 ) and a liquid moving device controller (or control module) 516 configured to control the operation of each liquid dispensing device 100A-D ( Figure 4 ) of valve 148( Figure 1 ) is controlled by a valve controller (or control module) 518. The liquid moving device controller 516 and the valve controller 518 can coordinate or synchronize the operation of the liquid moving devices 410A-D and the valve 148 as needed to control the flow of liquid through the common liquid input channel (inlet 124, manifold 120) and the individual liquid output channels (conduit 128, outlet 132), including the on / off state, flow rate, and dispense volume of each liquid dispensing device 100A-D. The control provided by the liquid moving device controller 516 and / or the valve controller 518 can be based at least in part on the flow rate sensor 152 ( Figure 1 ) receives the feedback measurement signal. The system controller 500 may also include a temperature control device controller (or control module) 520, which is configured to control the temperature control device 156 ( Figure 1, if provided), and in particular its heating and / or cooling elements, the control can be based at least in part on feedback measurement signals received from one or more temperature sensors as described above. The operation of the temperature control device controller 520 can be appropriately coordinated or synchronized with the operation of the liquid moving devices 410A-D and / or valve 148.

[0082] The system controller 500 may also include one or more sensor interfaces 522 configured to receive and process signals from one or more sensors provided with the liquid dispensing apparatus 100 or the liquid dispensing system 400 (e.g., flow rate sensor 152, temperature sensor of the temperature control device 156, etc.). Figure 1 , if provided), etc.) to receive feedback (e.g., measurement) signals. For example, the sensor interface 522 may be embodied in a separate firmware module or other electronic circuitry that is part of the microcontroller of the system controller 500. The sensor interface 522 may communicate with controllers of the system controller 500 (e.g., liquid moving device controller 516, valve controller 518, temperature control device controller 520, etc.) as needed to effectively control (e.g., set, adjust, record data, etc.) various operating parameters of the liquid dispensing device 100 or liquid dispensing system 400, such as the total liquid volume dispensed and / or liquid flow rate, liquid temperature, etc. The firmware or other electronic circuitry embodying such a controller may also be provided with the same microcontroller that includes the sensor interface 522, or may be provided as separate hardware from the system controller 500.

[0083] The system controller 500 may also include a container stage controller (or control module) 524 that is configured to control the operation of the container transport system 414, particularly the operation of the robot 422, thereby controlling the movement of the container stage 418 (particularly when supporting multiwell plates 236 or other types of liquid containers), including pre-programmed routes to and from selected outlets 132A-D of the liquid dispensing devices 100A-D. The operation of the container stage controller 524 can be coordinated or synchronized with the operation of the liquid moving devices 410A-D and / or the valve 148, depending on the requirements of the given method being implemented.

[0084] The system controller 500 may also include a sample / container tracker (or tracking module) 526. The sample / container tracker 526 may be configured to, for example, track (at various stages of the implemented method) the position of a container support 236 (e.g., a multiwell plate), the address or location of each container (e.g., well) 244A-L of a given container support 236, a condition indicating whether a given container 244A-L has been used (e.g., filled with liquid), identification or information regarding liquids and other materials dispensed into a given container or well 244A-L, etc. The operation of the sample / container tracker 526 may be coordinated or synchronized with the operation of other modules of the system controller 500 and / or components of the liquid dispensing system 400, as desired.

[0085] As described elsewhere herein, in some embodiments, the liquid dispensing system 400 can be part of (or at least operate in conjunction with) a larger system that includes one or more analytical instruments configured to measure or detect one or more properties or characteristics of a volume of liquid dispensed by the liquid dispensing system 400 into a container (e.g., a well of a multiwell plate 236), or to otherwise analyze the volume of liquid. In such embodiments, the system controller 500 can also include a data acquisition / signal conditioning module (DAQ) 528 configured to receive and process appropriate measurement signals output by the analytical instrument (e.g., from its appropriate detector). The DAQ 528 and / or other modules of the system controller 500 can also be configured to format the acquired data for presentation in graphical form via a GUI (e.g., a chromatogram, a mass spectrogram, an electropherogram, a sample image, a contour plot or "heat map" displaying 3D data, etc.). The operation of the DAQ 528 can be coordinated or synchronized with the operation of one or more modules of the liquid dispensing system 400 as needed. For example, the container transport system 414 can be configured to transport the multiwell plate 236 (or other container) from the liquid dispensing system 400 to one or more analytical instruments.

[0086] As understood by those skilled in the art and as desired, any of the above modules 516-528 may be embodied in hardware, firmware or software, or some combination of hardware, firmware and / or software.

[0087] It should be understood that Figure 4 and Figure 5 A high-level schematic diagram of an example of a system controller 500 and related components consistent with the present disclosure is provided. Other components may be included as needed for the actual implementation, which are not shown but will be understood by those skilled in the art. It is also understood that the system controller 500 is Figure 4 and Figure 5The various functional blocks and signal chains are arbitrarily positioned for illustrative purposes only and are not intended to be limiting in any way. Those skilled in the art will appreciate that, in practice, the functionality of the system controller 500 may be implemented in a variety of ways, not necessarily in the same manner. Figure 4 and Figure 5 The invention is carried out in the exact manner shown and described herein.

[0088] Figure 6 600 is a flowchart illustrating an example of a method for dispensing liquid according to an embodiment of the present disclosure. According to the method, a liquid dispensing device as described herein is provided (step 602). Therefore, the liquid dispensing device may include a manifold, a plurality of conduits, and a plurality of valves respectively arranged in the conduits, the manifold including an inlet, and the plurality of conduits respectively including a plurality of outlets. A plurality of containers as described herein are also provided (step 604). One or more containers (selected containers) are selected to receive the liquid (step 606). The volume (or amount, aliquot, etc.) of the liquid to be distributed to the selected containers is determined (step 608). According to one aspect of the method, the volume determined for at least one of the selected containers is different from the volume determined for at least one other container in the selected containers. The liquid is caused to flow through the inlet and manifold (i.e., a liquid flow is established) and enter each conduit (step 610). Then, the determined volume of liquid is distributed from the corresponding outlet in the plurality of outlets to the selected container by controlling the valve (step 612) and possible other components of the liquid dispensing device as described herein. As will be appreciated by those skilled in the art, one or more steps of the method (e.g., selecting a container, determining the volume to be dispensed, flowing the liquid (including flow conditions such as flow rate, temperature, etc.), and dispensing the determined volume) may be initiated or controlled by user input or by the system controller 500 based on data received from a sensor or stored in memory, or based on programmed instructions provided by software.

[0089] Figure 6 The order of steps 602-612 shown may be a typical example. However, it should be understood that the order of one or more steps in steps 602-612 may be changed, and some steps in steps 602-652 may be performed simultaneously.

[0090] In embodiments, flow chart 600 may represent a liquid dispensing device or system, or a portion of a liquid dispensing device or system, configured to perform steps 602-612. To this end, a controller (e.g., a processor, memory, and other components as understood by those skilled in the art) may be provided. Figure 4 and Figure 5The controller 500 shown in FIG. 5 controls the execution of one or more steps in steps 602-612, for example, by controlling the components of the liquid dispensing device or system involved in executing one or more steps in steps 602-612.

[0091] Figure 7 700 is a flowchart illustrating another example of a method for dispensing liquid according to an embodiment of the present disclosure. According to the method, a liquid dispensing device as described herein is provided (step 702). Thus, the liquid dispensing device may include a manifold, a plurality of conduits, and a plurality of valves respectively disposed in the conduits, the manifold including an inlet, and the plurality of conduits each including a plurality of outlets. Liquid is dispensed from one or more selected conduits of the plurality of conduits (step 704). The corresponding flow rate of the liquid in the selected conduits is measured (step 706). For each selected conduit, it is determined whether the measured flow rate deviates from the target flow rate or target flow rate range set for the selected conduit (step 708). For each selected conduit in which the measured flow rate is determined to deviate from the target flow rate or target flow rate range for the selected conduit, the valve operation of the valve in the selected conduit is adjusted (step 710). Generally, the valve operation determines the volume of liquid dispensed from the conduit / outlet associated with the valve, thereby determining the volume of liquid dispensed into the container below. In addition, the operation of the valve depends on whether the valve is operated according to a variable valve opening duration with a constant flow rate, or whether the valve itself is configured to vary the flow rate. Thus, examples of such valve operations include, but are not limited to, the duration of time that the valve is open (valve open duration), particularly in the case of a constant flow rate; or in the case of a variable flow rate valve, the flow rate set by the valve.

[0092] Figure 7 The order of steps 702-710 shown may be a typical example. However, it should be understood that the order of one or more steps in steps 702-710 may be changed, and some steps in steps 702-710 may be performed simultaneously.

[0093] In embodiments, flowchart 700 may represent a liquid dispensing device or system, or a portion of a liquid dispensing device or system, configured to perform steps 702-710. To this end, a controller (e.g., a processor, memory, and other components as understood by those skilled in the art) may be provided. Figure 4 and Figure 5 ) to control the execution of one or more of steps 702-710, for example, by controlling components of the liquid dispensing device or system involved in executing one or more of steps 702-750.

[0094] Example – Dispense Volume Adjustment Process

[0095] This example is based on the case of the liquid dispensing device described herein, each of which is configured with an unadjustable flow rate and a flow rate sensor (e.g. Figure 1 As shown), this limits the change of valve opening duration to be the only form of dispensing volume adjustment. This dispensing volume correction process can be used to correct the flow rate of subsequent batches as needed, or can be performed continuously for closed-loop operation.

[0096] 1) Time data is recorded by various device components at a frequency that depends on the device, but all data is referenced to an established time standard. For example, one component may record at 10 Hz, or ten times per second, and record relative to a standard clock time, while another component may record at 1000 Hz, or one thousand times per second. Both recordings are relative to a standard time (i.e., hh:mm:ss.ms), establishing the time points for each component to compare data between components.

[0097] 2) Device control system (such as Figure 4 and Figure 5 The system controller (shown) defines valve state data for each point in time, whether the valve is open or closed. The control system provides a valve actuation signal to each dispensing valve, which opens each valve until the signal goes out, closing the valve. This process delivers the dispensed fluid.

[0098] 3) Valve opening duration The valve opening timing is controlled by the device control system according to the valve flow rate table, which is designed to operate when using different numbers of nozzles (i.e. Figure 1 and Figure 4 The table is compiled to account for different flow rates when the nozzle is open (e.g., the outlet 132 shown), because the flow rate of one open nozzle will be slightly greater than the flow rate of the same nozzle when all nozzles are open. The valve open duration is calculated based on a combination of the desired dispense volume and the valve flow rate data from the table for a specific nozzle configuration, for example, based on the following relationship: ((valve flow rate in mL / s) × (valve open duration in s)) / (dispense volume in mL).

[0099] 4) Raw flow rate data is collected from the flow rate sensor that measures the dispensed fluid and is recorded by the device control system at each nozzle in time. The data record also identifies the device and nozzle location. Flow rate data is typically recorded continuously, and unneeded data is ignored. However, data logging can be activated only when needed.

[0100] 5) Dispense samples were initiated by the control system in a predetermined pattern designed to evaluate flow rates in various dispense nozzle configurations. Two such nozzle configurations were tested: one with only one nozzle flowing and one with all nozzles flowing. Additional test configurations can improve data quality, and there are no restrictions on the dispense patterns used for data collection. Examples include testing each nozzle individually rather than just one, testing groups of nozzles rather than just one or all, etc. Once the data is acquired, approximate flow rates can be calculated for all nozzle configurations, and the additional data reduces the relative error in the calculated flow rate values.

[0101] 6) Data analysis process for allocation volume adjustment

[0102] a. Valve Open Duration: For any dispense cycle, subtract the first valve open time point from the first valve closed time point to find the valve open duration, which is the time used to deliver a given volume of fluid. This is: Dispense Volume = Flow Rate x Valve Open Duration. Note that adjusting the valve open duration results in a change in the actual dispense volume.

[0103] b. Flow Duration Determination: After selecting the relevant raw flow rate data for the dispense cycle to be evaluated, the data is compared to predetermined thresholds to determine the flow start and flow stop time points. The flow start time point is subtracted from the flow stop time point to obtain the flow duration data point. The threshold value is greater than the highest value expected in normally noisy data when the valve is closed.

[0104] c. Flow Rate Zero Correction: For a subset of pre-dispense flow rate data points, the raw flow rate data with the valve closed is averaged to generate a zero offset value. The zero offset value is subtracted from the raw flow rate data between the flow start and flow stop time points to generate the corrected flow rate data.

[0105] d. Flow Rate and Volume Calculation (Average Method): During the dispense process, average the corrected flow rate data between the flow start and flow stop time points to produce the average flow rate. If necessary, multiply the average flow rate by the flow duration to produce the measured flow volume data point. Repeat this process for all nozzle configurations being evaluated.

[0106] e. Dispense Volume Adjustment: For each nozzle configuration, compare the average flow rate data to the flow rate set point according to the following formula: Corrected flow rate set point = average flow rate x correction factor, where correction factor = actual flow rate / measured flow rate. Enter the corrected flow rate set point into the valve flow rate table to override the set point that produced the incorrect dispense volume.

[0107] Exemplary embodiments

[0108] Exemplary embodiments provided in accordance with the presently disclosed subject matter include, but are not limited to, the following:

[0109] 1. A liquid dispensing device, comprising: a housing surrounding an interior of the device; a manifold disposed within the device and including an inlet; a plurality of conduits disposed within the device and in communication with the manifold, each including a plurality of outlets; and a plurality of actively controllable valves disposed in the conduits, each configured to control a corresponding liquid flow through the conduits, wherein the liquid dispensing device defines a common liquid input flow path in the manifold, and a plurality of liquid output flow paths extending from the manifold through the corresponding conduits and to the corresponding outlets.

[0110] 2. The liquid dispensing device according to embodiment 1, wherein the housing is box-shaped.

[0111] 3. The liquid dispensing device of embodiment 1 or 2, wherein the outlets are horizontally spaced apart from each other by a distance selected from the group consisting of: a distance in the range of 2 mm to 25 mm; a distance of 9.0 mm; a distance of 4.5 mm; a distance of 2.25 mm.

[0112] 4. The liquid dispensing device of any preceding embodiment, wherein the valve is configured for on / off flow control, variable flow rate control, or on / off flow control and variable flow rate control.

[0113] 5. The liquid dispensing device according to any one of the preceding embodiments, comprising one or more flow rate sensors respectively arranged at the conduit or the manifold or both the conduit and the manifold.

[0114] 6. The liquid dispensing device of embodiment 5, comprising a controller configured to control the valve based on output signals received from the one or more flow rate sensors.

[0115] 7. A liquid dispensing device according to embodiment 6, wherein the valve operation of the valve determines the dispensing volume of the liquid dispensed from the corresponding outlet for each liquid output flow path; and the controller is configured to control the valve operation to control the dispensing volume of the liquid dispensed from the outlet respectively.

[0116] 8. The liquid dispensing device of embodiment 7, wherein the valve operation comprises one of: a duration of time during which the corresponding valve is open; a flow rate set by the corresponding valve.

[0117] 9. A liquid dispensing device according to embodiment 7, wherein the controller is configured to: determine whether the dispensed volume is equal to the target volume or target volume range set for the corresponding outlet based on the output signal received from one or more flow rate sensors; and for any dispensed volume determined to be not equal to the target volume set for the corresponding outlet or outside the target volume range, adjust the valve operation of the corresponding valve to achieve the target volume or target volume range.

[0118] 10. A liquid dispensing device according to any one of the preceding embodiments, comprising a controller configured to control the following steps: selecting a selected outlet from which liquid is dispensed; determining the volume of liquid to be dispensed from the selected outlets; causing the liquid to flow through the inlet and the manifold and into the conduit; and dispensing the liquid from the corresponding selected outlet according to the determined volume through the control valve.

[0119] 11. A liquid dispensing device according to any one of the preceding embodiments, comprising a controller configured to control the following steps: selecting a selected container from a plurality of containers; determining the volume of liquid to be respectively dispensed into the selected containers; allowing the liquid to flow through the inlet and the manifold and into the conduit; and dispensing the liquid from the corresponding outlet of the plurality of outlets into the selected container according to the determined volume through the control valve.

[0120] 12. A liquid dispensing device according to any one of the preceding embodiments, comprising a controller configured to control the following steps: dispensing liquid from one or more selected conduits among a plurality of conduits; measuring the corresponding flow rate of the liquid in the selected conduits; for each selected conduit, determining whether the measured flow rate deviates from a target flow rate or a target flow rate range set for the selected conduit; and for each selected conduit in which the measured flow rate is determined to deviate from the target flow rate or the target flow rate range, adjusting the valve operation of the valve in the selected conduit.

[0121] 13. The liquid dispensing device of embodiment 12, wherein the valve operation comprises one of: a duration of time during which the corresponding valve is open; a flow rate set by the corresponding valve.

[0122] 14. The liquid dispensing device of any preceding embodiment, comprising a temperature control device configured to heat and / or cool the liquid in the conduit.

[0123] 15. The liquid dispensing device of embodiment 14, comprising a temperature sensor in communication with the temperature control device and configured to measure the temperature of the liquid in the conduit.

[0124] 16. The liquid dispensing device of embodiment 15, comprising a controller configured to control the temperature based on an output signal received from the temperature sensor.

[0125] 17. The liquid dispensing device of any preceding embodiment, comprising a plurality of fluid fittings, each of the plurality of fluid fittings being attached to or integral with the outlet and configured to engage with a corresponding fluid outlet component.

[0126] 18. The liquid dispensing device of any preceding embodiment, comprising a controller configured to control the valve.

[0127] 19. The liquid dispensing device of embodiment 18, wherein the controller is disposed on the housing or within the device.

[0128] 20. The liquid dispensing device of any preceding embodiment, comprising a reservoir in communication with the inlet and a fluid movement device configured to move liquid from the reservoir to the inlet.

[0129] 21. The liquid dispensing device of embodiment 20, wherein the fluid moving device comprises a pump.

[0130] 22. The liquid dispensing device of embodiment 20, wherein the fluid moving device comprises a pressure source configured to pressurize the reservoir to a controlled internal pressure.

[0131] 23. The liquid dispensing device of any one of embodiments 1-19, comprising a reservoir and a tube fluidly interconnecting the reservoir and the inlet, wherein the reservoir and the tube are configured to flow the liquid by gravity feed.

[0132] 24. A liquid dispensing system comprising a plurality of the liquid dispensing devices according to any one of the preceding embodiments, wherein the liquid dispensing devices are stacked horizontally such that the outlets of the liquid dispensing devices are arranged in a two-dimensional array.

[0133] 25. The liquid dispensing system of embodiment 24, wherein, for each liquid dispensing device, at least one outlet of the liquid dispensing device is aligned with corresponding outlets of other liquid dispensing devices along a straight line or a curve.

[0134] 26. The liquid dispensing system of embodiment 24 or 25, wherein the outlet of each liquid dispensing device is horizontally spaced apart by a uniform distance from the corresponding outlet of an adjacent one of the liquid dispensing devices.

[0135] 27. The liquid dispensing system of embodiment 24 or 25, wherein one or more outlets of the liquid dispensing device are horizontally spaced apart from outlets of adjacent ones of the liquid dispensing devices by uneven distances.

[0136] 28. The liquid dispensing system according to any one of embodiments 24-27, comprising a plurality of liquid reservoirs respectively connected to the inlet of the liquid dispensing device.

[0137] 29. The liquid dispensing system of embodiment 28, wherein the reservoirs are configured to be independently pressurized to separate internal pressures.

[0138] 30. The liquid dispensing system according to any one of embodiments 24-29 comprises a controller configured to control the following steps: selecting two or more selected liquid dispensing devices from the plurality of liquid dispensing devices; supplying two or more liquids to the corresponding inlets of the selected liquid dispensing devices; and dispensing the two or more liquids from the corresponding outlets of the selected liquid dispensing devices into one or more containers by controlling the valves of the selected liquid dispensing devices.

[0139] 31. A liquid dispensing system comprising: the liquid dispensing apparatus of any preceding embodiment; and a stage movable along one or more axes and configured to move a plurality of containers to and from the liquid dispensing apparatus.

[0140] 32. The liquid dispensing system of embodiment 31, wherein the outlets are horizontally spaced apart from one another at a uniform center-to-center outlet distance, and the outlet distance is equal to the spacing that the containers are spaced apart from one another.

[0141] 33. The liquid dispensing system of embodiment 31 or 32, wherein the controller is configured to control the station to move the plurality of containers to a dispensing position prior to dispensing, in which a selected container is positioned below a corresponding outlet.

[0142] 34. The liquid dispensing system of embodiment 33, wherein the controller is configured to move the plurality of containers along two or more axes.

[0143] 35. A method for dispensing liquid, the method comprising: providing a liquid dispensing device, the liquid dispensing device comprising a manifold, a plurality of conduits and a plurality of valves respectively arranged in the conduits, wherein the manifold comprises an inlet and the plurality of conduits respectively comprise a plurality of outlets; providing a plurality of containers; selecting a selected container from the plurality of containers to receive the liquid; determining the volume of the liquid to be respectively dispensed into the selected containers, wherein the volume determined for at least one of the selected containers is different from the volume determined for at least another of the selected containers; allowing the liquid to flow through the inlet and the manifold and into the conduits; and dispensing the liquid from the corresponding outlet of the plurality of outlets into the selected container according to the determined volume by controlling the valve.

[0144] 36. The method of embodiment 35, comprising, prior to dispensing, moving the plurality of containers to a dispensing position in which a selected container is positioned below a corresponding outlet.

[0145] 37. A method according to embodiment 36, wherein a plurality of containers are arranged in a two-dimensional array, the dispensing position is a first dispensing position, and the selected container is a first selected container in a first column of the array, and the method further comprises: after dispensing into the first selected container, moving the plurality of containers to a second dispensing position, in which the containers in the second column of the array are aligned with corresponding outlets of the plurality of outlets; and dispensing an additional determined volume of liquid from corresponding outlets of the plurality of outlets into the selected container in the second column.

[0146] 38. The method of any one of embodiments 35-37, wherein the container is a well of a multiwell plate.

[0147] 39. The method of any one of embodiments 35-38, wherein the valve is switchable between open and closed states, and the step of allocating comprises controlling the respective durations of time that the valve is in the open state.

[0148] 40. The method of any one of embodiments 35-38, wherein the valve is configured for a variable flow rate, and the step of dispensing comprises controlling a corresponding flow rate set by the valve.

[0149] 41. The method of any one of embodiments 35-40, comprising controlling the flow rate of the liquid by controlling the internal pressure of a reservoir in communication with the inlet.

[0150] 42. The method of any one of embodiments 35-41, wherein the step of dispensing comprises controlling the valve based on a corresponding flow rate sensed in the conduit.

[0151] 43. The method of any one of embodiments 35-42, comprising controlling the temperature of the liquid in the conduit while flowing the liquid.

[0152] 44. The method of embodiment 43, comprising controlling the temperature of the liquid based on a temperature sensed within the device of the liquid dispensing device.

[0153] 45. A method according to any one of embodiments 35-44, wherein: the liquid dispensing device is one of a plurality of liquid dispensing devices, each liquid dispensing device including a manifold, a plurality of conduits and a plurality of valves respectively arranged in the conduits, wherein each manifold includes an inlet and the conduits of each manifold include corresponding outlets; and the liquid dispensing devices are stacked horizontally so that the outlets of the liquid dispensing devices are arranged in a two-dimensional array.

[0154] 46. The method according to embodiment 45 comprises: selecting two or more selected liquid dispensing devices from a plurality of liquid dispensing devices; and supplying two or more liquids to the corresponding inlets of the selected liquid dispensing devices, wherein: the selecting step comprises selecting a selected container of the selected liquid dispensing device to receive the liquid; the determining step comprises determining the volume of the liquid to be respectively dispensed into the selected containers of the selected liquid dispensing device; and the dispensing step comprises dispensing the two or more liquids from the respective outlets of the selected liquid dispensing device into the selected containers according to the determined volume by controlling the valves of the selected liquid dispensing device.

[0155] 47. The method of embodiment 46, wherein at least one of the two or more liquids has a different composition than the remaining liquids of the two or more liquids.

[0156] 48. A method according to embodiment 46 or 47, wherein the plurality of liquid dispensing devices include at least a first liquid dispensing device and a second liquid dispensing device, and the dispensing step includes simultaneously dispensing a first liquid from the first liquid dispensing device and dispensing a second liquid from the second liquid dispensing device.

[0157] 49. A method according to embodiment 46 or 47, wherein the plurality of liquid dispensing devices include at least a first liquid dispensing device and a second liquid dispensing device, and the dispensing step includes sequentially dispensing the first liquid from the first liquid dispensing device and dispensing the second liquid from the second liquid dispensing device.

[0158] 50. A method according to any one of embodiments 46-49, wherein the plurality of liquid dispensing devices include at least a first liquid dispensing device and a second liquid dispensing device, the plurality of containers are arranged in a two-dimensional array, and the dispensing step includes: dispensing the first liquid from the first liquid dispensing device to one or more selected containers in a first column of the array; and dispensing the second liquid from the second liquid dispensing device to one or more selected containers in a second column of the array.

[0159] 51. A method according to any one of embodiments 46-49, wherein the multiple liquid dispensing devices include at least a first liquid dispensing device and a second liquid dispensing device, the multiple containers are arranged in a two-dimensional array, and the dispensing step includes: dispensing the first liquid from the first liquid dispensing device to one or more selected containers in a selected column in the array; and dispensing the second liquid from the second liquid dispensing device to one or more selected containers in the same selected column.

[0160] 52. The method of embodiment 51, comprising: prior to dispensing the first liquid, aligning the selected column with an outlet of a first liquid dispensing device; and prior to dispensing the second liquid, moving the plurality of containers to align the selected column with an outlet of a second liquid dispensing device.

[0161] 53. The method of embodiment 35, comprising one or more features of embodiments 1-34.

[0162] 54. A method for distributing liquid, the method comprising: providing a liquid distributing device, the liquid distributing device comprising a manifold, a plurality of conduits and a plurality of valves respectively arranged in the conduits, wherein the manifold comprises an inlet and the plurality of conduits respectively comprise a plurality of outlets; distributing liquid from one or more selected conduits among the plurality of conduits; measuring the corresponding flow rate of the liquid in the selected conduits; for each selected conduit, determining whether the measured flow rate deviates from a target flow rate or a target flow rate range set for the selected conduit; for each selected conduit in which the measured flow rate is determined to deviate from the target flow rate or the target flow rate range for the selected conduit, adjusting the valve operation of the valve in the selected conduit.

[0163] 55. The method of embodiment 54, wherein the valve operation comprises one of: a duration of time that the corresponding valve is open; a flow rate set by the corresponding valve.

[0164] 56. The method of embodiment 54, comprising one or more features of embodiments 1-52.

[0165] 57. A non-transitory computer-readable medium comprising instructions stored thereon, which, when executed on a processor, control or perform one or more steps of any one of embodiments 35-56.

[0166] 58. A liquid dispensing system comprising the non-transitory computer readable storage medium of embodiment 57.

[0167] It should 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 of the foregoing. The software may reside in a software memory (not shown) in a suitable electronic processing component or system, such as a processor. Figure 4 and Figure 5The system controller 500 schematically depicted in FIG. 5 may include an ordered list of executable instructions for implementing logical functions (i.e., "logic" may be implemented in digital form (such as digital circuits or source code, etc.) or in analog form (such as analog sources such as analog electricity, sound or video signals). The instructions may be executed within a processing module that includes, 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. In addition, the schematics depict a logical partitioning of functions with physical (hardware and / or software) implementations that are not limited by the architecture or physical layout of the functions. The system examples described herein may be implemented in various configurations and operated as hardware / software components in a single hardware / software unit, or as separate hardware / software units.

[0168] Executable instructions may be implemented as a computer program product having instructions stored therein, which, when executed by a processing module (e.g., Figure 4 and Figure 5 When the system controller 500 (schematically depicted in FIG) is executed, these instructions instruct the electronic system to execute the instructions. The computer program product can be selectively embodied in any non-transient computer-readable storage medium for use by or in combination with an instruction execution system, device or equipment, such as a system based on an electronic computer, a system containing a processor, or other systems that can selectively obtain instructions from the instruction execution system, device, or equipment and execute instructions. In the context of the present disclosure, a computer-readable storage medium is any non-transient device that can store a program for use by or in combination with an instruction execution system, device or equipment. A non-transient computer-readable storage medium can be, for example, an electronic, magnetic, optical, electromagnetic, infrared or semiconductor system, device or equipment. A non-exhaustive list of more specific examples of non-transitory computer-readable media includes: an electrical connector having one or more wires (electronic); a portable computer disk (magnetic); random access memory (electronic); read-only memory (electronic); erasable programmable read-only memory, such as flash memory, etc. (electronic); optical disk storage, such as CD-ROM, CD-R, CD-RW (optical); and digital versatile disk storage, i.e., DVD (optical). Note that the non-transitory computer-readable storage medium may even be paper or other suitable medium on which the program is printed, as the program may be captured electronically, for example, by optical scanning of the paper or other medium, and then compiled, interpreted, or otherwise processed in an appropriate manner, if necessary, and then stored in computer memory or machine storage.

[0169] It should also be understood that the terms "signal communication" or "electrical communication" as used herein refer to the ability of two or more systems, devices, components, modules, or submodules to communicate with each other via signals propagating over some type of signal path. The signal can be a communication, power, data, or energy signal that can transfer information, power, or energy from a first system, device, component, module, or submodule to a second system, device, component, module, or submodule along a signal path between a first and a second system, device, component, module, or submodule. The signal path can include physical, electrical, magnetic, electromagnetic, electrochemical, optical, wired, or wireless connections. The signal path can also include additional systems, devices, components, modules, or submodules between the first and second systems, devices, components, modules, or submodules.

[0170] More generally, terms such as "in communication" and "in communication with..." (e.g., a first component is "in communication with" a second component) are used herein to refer to a structural, functional, mechanical, electrical, signal, optical, magnetic, electromagnetic, ionic, or fluid relationship between two or more components or elements. Thus, the fact that one component is referred to as being in communication with a second component does not exclude the possibility of other components being operatively associated or engaged between and / or with the first and second components.

[0171] It will be appreciated that various aspects or details of the invention may be modified without departing from the scope of the invention. Furthermore, the foregoing description is intended to be illustrative only and not restrictive - the invention being defined by the claims.

Claims

1. A liquid dispensing device, comprising: a housing that surrounds the interior of the device; a manifold disposed within the device and comprising an inlet; a plurality of conduits disposed within the device and in communication with the manifold, each conduit comprising a plurality of outlets; and a plurality of actively controllable valves, each disposed in the conduit, the valves being configured to control a corresponding flow of liquid through the conduit, The liquid distribution device defines a common liquid input flow path in the manifold, and a plurality of liquid output flow paths extending from the manifold through respective conduits and to respective outlets. 2 . The liquid dispensing device of claim 1 , comprising one or more flow rate sensors disposed at the conduit or at the manifold or at both the conduit and the manifold. 3 . The liquid dispensing apparatus of claim 2 , comprising a controller configured to control the valve based on output signals received from the one or more flow rate sensors.

4. The liquid dispensing device according to claim 3, wherein: For each liquid output flow path, valve operation of the valve determines a dispensed volume of liquid dispensed from the corresponding outlet; as well as The controller is configured to control the operation of the valves to control the dispensing volumes of the liquids dispensed from the respective outlets.

5. The liquid dispensing device according to claim 4, wherein: The valve operation includes one of the following: the duration of the corresponding valve opening; The flow rate is set by the corresponding valve.

6. The liquid dispensing device according to claim 4, wherein: The controller is configured to: determining, based on the output signals received from one or more of the flow rate sensors, whether the dispense volume is equal to a target volume or target volume range set for a corresponding outlet; as well as For any dispense volume determined to be not equal to the target volume set for the corresponding outlet or outside the target volume range, valve operation of the corresponding valve is adjusted to achieve the target volume or the target volume range.

7. The liquid dispensing device according to claim 1, comprising a controller configured to control the following steps: selecting a selected outlet and dispensing liquid from the selected outlet; determining the volumes of liquids dispensed from the respective selected outlets; allowing a liquid to flow through the inlet and the manifold and into the conduit; and Liquid is dispensed according to a determined volume from the corresponding selected outlet by controlling the valve.

8. The liquid dispensing device of claim 1 , comprising a controller configured to control the following steps: dispensing liquid from one or more selected ones of the plurality of conduits; measuring a corresponding flow rate of the liquid in the selected conduit; for each selected conduit, determining whether the measured flow rate deviates from a target flow rate or target flow rate range set for the selected conduit; For each selected conduit in which the measured flow rate is determined to deviate from the target flow rate or the target flow rate range, valve operation of the valve in the selected conduit is adjusted.

9. The liquid dispensing device of claim 1 , comprising at least one of the following features: a fluid reservoir in communication with the inlet, and a fluid moving device configured to move fluid from the reservoir to the inlet; a liquid reservoir in communication with the inlet, and a fluid moving device configured to cause liquid to flow from the liquid reservoir to the inlet, wherein The fluid moving device includes a pump; a fluid reservoir in communication with the inlet, and a fluid moving device configured to cause fluid to flow from the reservoir to the inlet, wherein the fluid moving device includes a pressure source configured to pressurize the reservoir to a controlled internal pressure; A reservoir and a tube fluidly interconnecting the reservoir and the inlet, wherein the reservoir and the tube are configured to flow liquid via gravity feed.

10. A liquid dispensing system comprising a plurality of liquid dispensing devices according to claim 1, wherein: The liquid dispensing devices are stacked horizontally so that the outlets of the liquid dispensing devices are arranged in a two-dimensional array, and the liquid dispensing system further comprises at least one of the following features: wherein, for each liquid dispensing device, at least one outlet of the liquid dispensing device is aligned with corresponding outlets of other liquid dispensing devices along a straight line or a curve; wherein the outlet of each liquid dispensing device is horizontally spaced apart from the corresponding outlet of an adjacent liquid dispensing device in the liquid dispensing device by a uniform distance; wherein one or more outlets of the liquid dispensing device are horizontally spaced apart from adjacent liquid dispensing devices in the liquid dispensing device at uneven distances; comprising a plurality of liquid reservoirs respectively in communication with the inlets of the liquid dispensing device; A plurality of liquid reservoirs are included that are respectively in communication with the inlet of the liquid dispensing device, wherein the liquid reservoirs are configured to be independently pressurized to separate internal pressures.

11. A liquid dispensing system comprising: a plurality of liquid dispensing devices according to claim 1, wherein the liquid dispensing devices are stacked horizontally such that the outlets of the liquid dispensing devices are arranged in a two-dimensional array; and The controller is configured to control the following steps: selecting two or more selected liquid dispensing devices from the plurality of liquid dispensing devices; supplying two or more liquids to corresponding inlets of the selected liquid dispensing device; and By controlling the valve of the selected liquid dispensing device, amounts of two or more liquids are dispensed from corresponding outlets of the selected liquid dispensing device into one or more containers.

12. A liquid dispensing system comprising: The liquid dispensing device according to claim 1; and A stage is movable along one or more axes and configured to move a plurality of containers to and from the liquid dispensing apparatus.

13. A method for dispensing a liquid, the method comprising: Providing a liquid distribution device comprising a manifold, a plurality of conduits, and a plurality of valves respectively disposed in the conduits, wherein the manifold comprises an inlet, and the plurality of conduits respectively comprise a plurality of outlets; Provide multiple containers; selecting a selected container from the plurality of containers to receive the liquid; determining volumes of liquid to be dispensed into the respective selected containers, wherein the volume determined for at least one of the selected containers is different from the volume determined for at least another of the selected containers; flowing a liquid through the inlet and the manifold and into the conduit; and By controlling the valve, liquid is dispensed from a corresponding outlet of the plurality of outlets into the selected container according to the determined volume.

14. The method according to claim 13, wherein The plurality of containers are arranged in a two-dimensional array, the dispense position is a first dispense position, and the selected container is a first selected container of a first column of the array, and the method further comprises: After the step of dispensing into the first selected container, moving the plurality of containers to a second dispensing position in which containers of a second column of the array are aligned with corresponding ones of the plurality of outlets; and An additional determined volume of liquid is dispensed from corresponding ones of the plurality of outlets into selected containers of the second column.

15. The method of claim 13, wherein: The liquid distribution device is one of a plurality of liquid distribution devices, each liquid distribution device comprising a manifold, a plurality of conduits, and a plurality of valves respectively disposed in the conduits, wherein each manifold comprises an inlet, and the conduits of each manifold comprise a plurality of corresponding outlets; and The liquid dispensing devices are stacked horizontally such that the outlets of the liquid dispensing devices are arranged in a two-dimensional array.

16. The method according to claim 15, comprising: selecting two or more selected liquid dispensing devices from the plurality of liquid dispensing devices; and supplying two or more liquids to respective inlets of the selected liquid dispensing device, wherein: The step of selecting includes selecting a selected container of the selected liquid dispensing device to receive the liquid; The step of determining includes determining volumes of liquid to be dispensed into the selected containers of the selected liquid dispensing devices, respectively; and The step of dispensing includes dispensing the two or more liquids from respective outlets of the selected liquid dispensing device into the selected container according to the determined volumes by controlling the valve of the selected liquid dispensing device.

17. The method according to claim 16, wherein The plurality of liquid dispensing devices include at least a first liquid dispensing device and a second liquid dispensing device, and further include one or more of the following features: The step of dispensing includes simultaneously dispensing a first liquid from the first liquid dispensing device and a second liquid from the second liquid dispensing device; The step of dispensing includes sequentially dispensing a first liquid from the first liquid dispensing device and dispensing a second liquid from the second liquid dispensing device; The plurality of containers are arranged in a two-dimensional array, and the step of dispensing comprises: dispensing a first liquid from the first liquid dispensing device into one or more selected containers in a first column of the array; and dispensing a second liquid from the second liquid dispensing device into one or more selected containers in a second column of the array; The plurality of containers are arranged in a two-dimensional array, and the step of dispensing comprises: dispensing a first liquid from the first liquid dispensing device into one or more selected containers in a selected column of the array; and dispensing a second liquid from the second liquid dispensing device into one or more of the selected containers in the same selected column.

18. The method according to claim 13, comprising: prior to dispensing a first liquid, aligning the selected column with the outlet of the first liquid dispensing device; and Prior to dispensing the second liquid, the plurality of containers are moved to align the selected column with the outlet of the second liquid dispensing device.

19. A method for dispensing a liquid, the method comprising: Providing a liquid distribution device comprising a manifold, a plurality of conduits, and a plurality of valves respectively disposed in the conduits, wherein the manifold comprises an inlet, and the plurality of conduits respectively comprise a plurality of outlets; dispensing liquid from one or more selected ones of the plurality of conduits; measuring a corresponding flow rate of the liquid in the selected conduit; for each selected conduit, determining whether the measured flow rate deviates from a target flow rate or target flow rate range set for the selected conduit; For each selected conduit in which the measured flow rate is determined to deviate from the target flow rate or the target flow rate range for the selected conduit, valve operation of the valve in the selected conduit is adjusted.

20. The method according to claim 19, wherein The valve operation includes one of the following: the duration of the corresponding valve opening; The flow rate is set by the corresponding valve.

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