Robotic systems and methods for piercing a sealed well plate

Abstract

A robotic system includes a gantry with multiple channels and a device fixed to each channel, a stage for a well plate, and a computer readable media storing instructions. In a first configuration, a controller positions the gantry over a first column of wells, a first device over a first well, a second device over a ledge of a first end of the well plate, and a third device over the ledge at a second end of the well plate. In a second configuration, the controller moves the devices in a Z‑direction, such that the first device punctures a cover of the well plate, and the second and third devices contact or are positioned above the ledge. In a third configuration, the controller moves the first device in the Z-direction, while the second and third devices remain in place to inhibit the well plate from lifting with the first device.

Description

Attorney Docket No. 00316-0041-00304ROBOTIC SYSTEMS AND METHODS FOR PIERCING A SEALED WELL PLATECROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 714,484, filed October 31 , 2024, the entirety of which is incorporated herein by reference.TECHNICAL FIELD

[0002] The present disclosure relates generally to systems and methods for automating access of one or more samples contained within a sealed well plate.BACKGROUND

[0003] Well plates are commonly used to hold a plurality of samples during processing. In some aspects, the well plate may be covered or sealed, for example, to prevent cross-contamination of samples contained within the well plate, to prevent contamination of the samples from external sources, or to prevent spilling. Accordingly, accessing individual samples, or other materials, within the well plate may require removal of the cover, thus increasing the risk of contamination and / or spillage of the contents within the well plate. Removal of the cover or seal may also add an extra step during the processing procedure and may be awkward to perform, particularly if automated sample processing systems are used. However, accessing individual samples contained within a well plate without removing the seal or cover may be challenging. As an example, if pipette tip is used to puncture a seal, the seal may stick to the pipette tip as the pipette tip is removed from the well plate, thus causing the well plate to move, which may cause spills, cross-contamination, or other issues.Attorney Docket No. 00316-0041-00304

[0004] The present disclosure is directed to addressing one or more of these above-referenced challenges. The background description provided herein is for the purpose of generally presenting context of the disclosure. Unless otherwise indicated herein, the materials described in this section are not prior art to the claims in this application and are not admitted to be prior art, or suggestions of the prior art, by inclusion in this section.SUMMARY OF THE DISCLOSURE

[0005] In summary, one aspect provides a robotic system comprising a movable gantry having a plurality of channels, a stage above which the gantry is configured to move, and one or more computer readable media storing instructions that are executable by one or more processors. The plurality of channels includes at least a first channel, a second channel, and a third channel. At least some of the plurality of channels are movable relative to one another along a length of the gantry.

[0006] A first device is fixed or is configured to be fixed to the first channel, a second device is fixed or is configured to be fixed to the second channel, and a third device is fixed or is configured to be fixed to the third channel. The stage is configured to receive a well plate having (i) a plurality of wells, (ii) an outer ledge that does not contain any wells, and (iii) a cover at least partially covering the plurality of wells. The one or more processors are operably coupled to a controller associated with the gantry.

[0007] When the well plate is received on the stage, the controller is configured to perform operations to, in a first configuration, position the gantry over a first column of wells of the well plate, position the first device over a first well of the first column of wells, position the second device over a portion of the ledge of a firstAttorney Docket No. 00316-0041-00304 end of the first column of wells, and position the third device over a portion of the ledge at a second end of the first column of wells.

[0008] In a second configuration, the controller moves the first device, the second device, and the third device in a Z-direction towards the well plate, such that the first device punctures the cover of the well plate above the first well, and such that the second device and the third device either contact the ledge or are positioned above the ledge.

[0009] In a third configuration, the controller moves the first device in the Z- direction away from the well plate, while the second device and the third device remain in place to inhibit the well plate from lifting in the Z-direction with the first device.

[0010] Any of the devices disclosed herein may include any of the following features, additionally or alternatively, in any combination. The first device may be a pipette. In the second configuration, the second device and the third device may not be in contact with the ledge and are positioned approximately 0.1 cm to approximately 0.5 cm above the ledge.

[0011] The first well may contain a liquid. The one or more computer readable media storing instructions that are executable by the one or more processors may further be configured to cause the controller to perform operations to, in a fourth configuration, reposition at least one of the gantry or the first device such that the device is positioned in a different location over the first well, move the first device in the Z-direction towards the well plate such that the first device punctures the cover of the well plate above the first well, and move the first device in the Z-direction away from the well plate. The fourth configuration may be performed a plurality of times.Attorney Docket No. 00316-0041-00304

[0012] In the second configuration, the first device may move in the Z- direction to a position within the first well above a surface of the liquid within the first well.

[0013] In the fourth configuration, the first device may move in the Z-direction to a position within the first well below the surface of the liquid within the first well.

[0014] The fourth configuration may be performed a plurality of times, and all but a last time the fourth configuration is performed, the first device may move in the Z-direction to a position within the first well above a surface of the liquid within the first well. The last time the fourth configuration is performed, the first device may move in the Z-direction to a position within the first well and below a surface of the liquid within the first well, and the liquid may be aspirated by the device.

[0015] The fourth configuration may be performed a plurality of times, and the second device and the third device may move in a Z-direction away from the well plate after the first device is moved in the Z-direction away from the well plate each time.

[0016] The one or more computer readable media storing instructions that are executable by the one or more processors may be further configured to cause the controller to perform operations to, in a fifth configuration, move the second device and the third device in a Z-direction away from the well plate.

[0017] The one or more computer readable media may be further configured to cause the controller to perform operations in the second configuration to cause the first device to inject a liquid into the first well after having been moved in the Z- direction towards the well plate.

[0018] The one or more computer readable media storing instructions that are executable by the one or more processors are further configured to cause theAttorney Docket No. 00316-0041-00304 controller to perform operations to, in a fourth configuration, move the second device and the third device in a Z-direction away from the well plate.

[0019] In another example, a method includes receiving a well plate in an automated robotic system. The well plate has (i) a plurality of wells, (ii) an outer ledge that does not contain any wells, and (iii) a cover at least partially covering the plurality of wells. The method may further include positioning a gantry over a first column of wells of the well plate, wherein the gantry includes a pipette operably connected thereto, a first device, and a second device, positioning the pipette over a first well of the first column of wells, positioning the first device over a portion of the ledge at a first end of the first column of wells, positioning the second device over a portion of the ledge at a second end of the first column of wells, moving the pipette, the first device, and the second device in a Z-direction towards the well plate, such that the pipette punctures the cover of the well plate above the first well, and such that the first device and the second device either contact the ledge or are positioned above the ledge, and moving the pipette in the Z-direction away from the well plate, while the first device and the second device remain in place to inhibit the well plate from lifting in the Z-direction with the pipette.

[0020] Any of the devices disclosed herein may include any of the following features, additionally or alternatively, in any combination. The method may further comprise transmitting, using one or more processors of the automated robotic system, one or more instructions to a controller that cause the controller to perform operations. The operations may include positioning the gantry over the first column of wells of the well plate; positioning the pipette over the first well of the first column of wells; positioning the first device over the portion of the ledge at the first end of the first column of wells; positioning the second device over the portion of the ledge atAttorney Docket No. 00316-0041-00304 the second end of the first column of wells; moving the pipette, the first device, and the second device in a Z-direction towards the well plate; and moving the pipette in the Z-direction away from the well plate.

[0021] The method may further include moving the first device and the second device in the Z-direction away from the well plate.

[0022] The method may further include repositioning at least one of the gantry or the pipette such that the pipette is positioned in a different location over the first well, moving the pipette in the Z-direction towards the well plate such that the first device punctures the cover of the well plate above the first well, and moving the pipette in the Z-direction away from the well plate.

[0023] The repositioning step, the moving the pipette in the Z-direction towards the well plate step, and the moving the pipette in the Z-direction away from the well plate step may be repeated multiple times either to form multiple openings in the cover above the well plate or to form a widened opening in the cover above the well plate. All but a last time the repeated steps are performed, the pipette may move in the Z-direction towards the well plate to a position within the first well above a surface of the liquid within the first well. The last time the repeated steps are performed, the pipette may move in the Z-direction towards the well plate to a position within the first well below the surface of the liquid within the first well and may aspirate the liquid within the first well before moving the pipette in the Z- direction away from the well plate.

[0024] Each time the pipette is moved in the Z-direction away from the well plate, the first device and the second device remain in place to inhibit the well plate from lifting in the Z-direction with the pipette. Each time the pipette is moved in the Z- direction away from the well plate, the first device and the second deviceAttorney Docket No. 00316-0041-00304 subsequently move in the Z-direction away from the well plate, and the first device and the second device also move in the Z-direction towards the well plate when the pipette is moved in the Z-direction towards the well plate.

[0025] Moving the first device and the second device in the Z-direction towards the well plate comprises positioning the first device and the second device approximately 0.1 cm to approximately 0.5 cm above the ledge.

[0026] The foregoing is a summary and thus may contain simplifications, generalizations, and omissions of detail; consequently, those skilled in the art will appreciate that the summary is illustrative only and is not intended to be in any way limiting.

[0027] For a better understanding of the embodiments, together with other and further features and advantages thereof, reference is made to the following description, taken in conjunction with the accompanying drawings. The scope of the invention will be pointed out in the appended claims.

[0028] The singular forms “a,” “an,” and “the” include plural reference unless the context dictates otherwise. The terms “approximately” and “about” refer to being nearly the same as a referenced number or value. As used herein, the terms “approximately” and “about” generally should be understood to encompass ± 10% of a specified amount or value. The use of the term “or” in the claims and specification is used to mean “and / or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or.” As used herein, the terms “comprises,” “comprising,” “including,” “having,” or other variations thereof, are intended to cover a non-exclusive inclusion such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements, but may includeAttorney Docket No. 00316-0041-00304 other elements not expressly listed or inherent to such a process, method, article, or apparatus. Additionally, the term “exemplary” is used herein in the sense of “example,” rather than “ideal.” In addition, the term “between” used in describing ranges of values is intended to include the minimum and maximum values described herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments and together with the description, serve to explain the principles of the disclosure.

[0030] FIG. 1 . depicts a top-down schematic view of an exemplary system, according to aspects of this disclosure.

[0031] FIG. 2 depicts a side view of the exemplary system of FIG. 1 , according to aspects of this disclosure.

[0032] FIG. 3 depicts a flow chart of an exemplary method, according to aspects of this disclosure.

[0033] FIGs. 4A-4D depict various stages of an exemplary method, according to aspects of this disclosure.

[0034] FIG. 5 depicts an exemplary system environment for executing the methods described herein, according to aspects of this disclosure.

[0035] FIG. 6 depicts an example computing system, according to aspects of this disclosure.

[0036] FIGs. 7A-7C each depict an exemplary device, according to aspects of this disclosure.Attorney Docket No. 00316-0041-00304DETAILED DESCRIPTION OF EMBODIMENTS

[0037] Aspects of the present disclosure are directed towards automated robotic systems and methods for accessing individual samples contained in wells of a sealed well plate. The embodiments discussed herein may assist in overcoming such challenges.

[0038] The subject matter of the present disclosure will now be described more fully hereinafter with reference to the accompanying drawings, which form a part hereof, and which show, by way of illustration, specific exemplary embodiments. An embodiment or implementation described herein as “exemplary” is not to be construed as preferred or advantageous, for example, over other embodiments or implementations; rather, it is intended to reflect or indicate that the embodiment(s) is / are “example” embodiment(s). Subject matter may be embodied in a variety of different forms and, therefore, covered or claimed subject matter is intended to be construed as not being limited to any exemplary embodiments set forth herein; exemplary embodiments are provided merely to be illustrative. Likewise, a reasonably broad scope for claimed or covered subject matter is intended. Among other things, for example, subject matter may be embodied as methods, devices, components, or systems. Accordingly, embodiments may, for example, take the form of hardware, software, firmware, or any combination thereof. The following detailed description is, therefore, not intended to be taken in a limiting sense.

[0039] Throughout the specification and claims, terms may have nuanced meanings suggested or implied in context beyond an explicitly stated meaning. Likewise, the phrase “in one embodiment” or “in some embodiments” as used herein does not necessarily refer to the same embodiment and the phrase “in another embodiment” as used herein does not necessarily refer to a different embodiment. ItAttorney Docket No. 00316-0041-00304 is intended, for example, that claimed subject matter include reasonable combinations of exemplary embodiments in whole or in part.

[0040] The terminology used below may be interpreted in its broadest reasonable manner, even though it is being used in conjunction with a detailed description of certain specific examples of the present disclosure. Indeed, certain terms may even be emphasized below; however, any terminology intended to be interpreted in any restricted manner will be overtly and specifically defined as such in this Detailed Description section.

[0041] FIG. 1 illustrates a top-down view of an exemplary system 100. FIG. 2 illustrates a side view of exemplary system 100. FIGs. 1 and 2 may be referred to interchangeably throughout the following description. For example, as shown in both FIGs. 1 and 2, system 100 may be an automated robotic liquid handler having a stage, or a base, 102 on which a well plate 104 may be positioned. During processing, a well plate 104 may be received on base 102. Well plate 104 may include a plurality of wells 106 arranged in a series of rows and columns. As shown in FIG. 1 , well plate 104 may include 96 individual wells 106. However, well plate 104 may include any number of wells 106 (e.g., six wells, 12 wells, 24 wells, 48 wells, 384 wells, etc.). The plurality of wells 106 may be referred to herein simply as “wells 106,” for example, when referring to two or more wells, or as “well 106” when referring to a single well. In an aspect, one or more features of exemplary system 100 (e.g., movements of the automated robotic liquid handler) may be controlled by computer instructions generated from a central controller, e.g., as described below with reference to FIGS. 5 and 6.

[0042] Wells 106 are illustrated in FIG. 2 using broken lines, for example, to illustrate the presence and position of wells 106 on well plate 104 in a side view.Attorney Docket No. 00316-0041-00304Some of wells 106 may be visible from the side, for example, due to well plate 104 being translucent, transparent, or semi-transparent, although a well plate of any material may be used. A cover 105 may extend over one or more wells 106. Cover 105 may be comprised of, for example, a metallic foil or a plastic material. In some aspects, cover 105 may form a seal over each well 106. For example, cover 105 may be fixed to or otherwise create a seal with well plate 104 in a space defined between wells 106 and / or in a space defined around each well 106. In these aspects, cover 105 may seal each well 106. Cover 105 may be attached to well plate 104 in any suitable manner, e.g., heat-sealed, with adhesive, via friction fit or snap fit, etc.

[0043] Wells 106 may each have a same diameter A1 . Wells 106 may each be spaced equally apart from one another. For example, a first distance D1 may define a shortest distance between center points of two adjacent wells 106. First distance D1 may be the same between adjacent wells 106 in different rows and / or between adjacent wells 106 in different columns. A second distance D2 may define a shortest length of a column of wells, for example, as measured between the center points of a first and last well 106 in a same column.

[0044] A third distance D3 may be defined as a shortest distance between the center points of a first and last well 106 in a same row. A fourth distance D4 may be defined as a shortest distance between a center point of a well that is in the first row or a last row of the plurality of wells 196 and an outer edge 108 of well plate 104. A fifth distance D5 may be defined as a shortest distance between a center point of a well that is in the first column or a last column and outer edge 108 of well plate 104.

[0045] Described in further detail below, diameter A1 , distances D1 , D2, D3, D4, D5, and / or the overall dimensions (e.g., a length, a width, and / or a depth) of wellAttorney Docket No. 00316-0041-00304 plate 104 may be provided as inputs into a software configured to control one or more aspects of system 100. In some aspects, diameter A1 , distances D1 , D2, D3, D4, D5, and / or the overall dimensions of well plate 104 may be observed, calculated, or otherwise determined for each individual well plate 104 as it is being handled by the system. As an example, an imaging system may capture an image of well plate 104 prior to or during handling operations, and the diameter A1 , distances D1 , D2, D3, D4, D5, and / or the overall dimensions of well plate 104 may be determined by a central controller from the images. As another example, a measurement system may use any appropriate touch-free measurement system to directly determine the diameter A1 , distances D1 , D2, D3, D4, D5, and / or the overall dimensions of well plate 104. In other aspects, diameter A1 , distances D1 , D2, D3, D4, D5, and / or the overall dimensions (e.g., a length, a width, and / or a depth) of well plate 104 may be standard for all well plates used in the automated robotic system, and thus may be stored in memory in the system.

[0046] A ledge 110 of well plate 104 may be defined, for example, around a perimeter of wells 106. Ledge 110 may be a planar surface defined between an outer edge of each well 106 defining a perimeter of wells 106 and outer edge 108 of well plate 104. A first width W1 of ledge 110 may be defined as a shortest distance between outer edge 108 and an outer edge of a well in the first row or the last row of wells 106. A second width W2 of ledge 110 may be defined as a shortest distance between outer edge 108 and the outer edge of a well in the first column or the last column of wells 106. First width W1 and second width W2 may be a same dimension or may be a different dimension. As will be described in further detail below, ledge 110 may be used to provide a counter force to prevent well plate 105 from lifting from stage 102 when accessing wells 106.Attorney Docket No. 00316-0041-00304

[0047] A robotic gantry 112 having a plurality of moveable channels 114 may extend over stage 102 in a Y-direction. In these aspects, shown in greater detail in FIG. 2, gantry 112 may be elevated over stage 102. Although not shown, one or both ends of gantry 112 may be coupled to a support or rail. The support or rail may enable movement of gantry 112 relative to stage 102. In these aspects, gantry 112 may be movable in an X-direction over stage 102 and / or a Z-direction towards or away from stage 102. Each channel 114 may be independently movable relative to one another in both a Y-direction (e.g., along a length of gantry 112) and a Z- direction (e.g., towards or away from stage 102). For example, a first channel 114A may be independently movable between a second channel 114B and a third channel 1140. Movement of each of first channel 114A, second channel 114B, and third channel 114C is illustrated using arrows extending along a portion of a length of gantry 112 in FIGs. 1 and 2. In an aspect, movement of some or all of the channels 114, and / or any other controllable component of robotic gantry 112, may be governed by a controller that receives instructions from a computer, e.g., as further described herein in association with FIGS. 5 and 6.

[0048] In some aspects, gantry 112 may include eight independent channels 114 (as illustrated in FIG. 1 ). Alternatively, gantry 112 may include six channels 114 (as illustrated in FIG. 2). In further aspects, gantry 112 may include fewer or additional channels 114 arranged on a same Y-axis, as defined by gantry 112. Each channel 114 may have a same diameter A2. Although one channel (e.g., first channel 114A) is illustrated between second channel 114B and third channel 114C, additional channels (e.g., two or more channels) may be movably disposed between second channel 114B and third channel 114C. In some aspects, the number of channels 114 on gantry 112 may correspond to the number of rows of wells 106 onAttorney Docket No. 00316-0041-00304 well plate 104. Further, although gantry 112 is depicted in FIG. 1 as extending along the Y-axis and moving along the X-axis, gantry 112 may have any suitable orientation. For example, gantry 112 may extend along the X-axis and may be movable along the Y-axis.

[0049] In other aspects, gantry 112 may be stationary and stage 102 may be configured to move relative to gantry 112. For example, stage 102 may be configured to move in each of the X-, Y-, or Z-axes relative to gantry 112.

[0050] As will be described in further detail below, one or more channels 114 (e.g., first channel 114A) may be active to permit fluid to flow to or from each respective channel 114. For example, one or more active channels 114 (e.g., first channel 114A) may be configured to aspirate and / or inject a fluid (e.g., a liquid or gas). Two or more other channels 114 (e.g., second channel 114B and / or third channel 114C) may be inactive or configured to neither aspirate nor inject a fluid. Aspiration and / or injection of the fluid within first channel 114A may be controlled via one or more switches or buttons and / or inputs provided into the software of system 100. As will be described in further detail below, inactive channels 114 (e.g., second channel 114B and / or third channel 114C) may be configured to maintain a position of well plate 104 on stage 102 and / or prevent well plate 104 from being lifted off of stage 102. In some aspects, all channels 114 may be active, but fewer than all channels may actually aspirate or inject fluid during use.

[0051] In some aspects, additional channels 114 may be inoperable, or inactive. For example, channel(s) 114 disposed between first channel 114A and second channel 114B or third channel 1140 may be inactive (e.g., not configured to permit fluid to or from each respective channel), but may prevent first channel 114A from abutting second channel 114B or third channel 114C during operation. In theseAttorney Docket No. 00316-0041-00304 aspects, the additional inactive channels 114, if included, may prevent access to one or more wells 106 of well plate 104.

[0052] One or more channels 114 may be configured to removably or permanently receive a device attached thereto. As examples, suitable devices may include one or more of a pipette, a tip, a rod, or a combination thereof. Exemplary devices are shown and described below with respect to FIGs. 7A-7D. The devices fixed to the channels may be the same type of device or may be different types of devices, and may be formed of the same or different materials. As shown in more detail in FIG. 2, a device such as a tip, or a pipette, may be fixed (either removably or permanently) to one or more channels 114. For example, a first pipette 116A may be fixed to first channel 114A, a second pipette 116B may be fixed to second channel 114B, and a third pipette 116C may be fixed to third channel 114C. Additional pipettes may be fixed to additional channels 114. Each pipette 116A, 116B, 1160 may extend from each respective channel 114A, 114B, 114C in a Z- direction. In other words, each pipette 116A, 116B, 116C may extend towards stage 102 and, thus, towards well plate 104 on stage 102.

[0053] A user may manually attach or couple each pipette 116A, 116B, 116C to respective channels 114A, 114B, 114C. Additionally or alternatively, each pipette 116A, 116B, 116 may be attached to respective channels 114A, 114B, 114 robotically (e.g., without intervention by the user). For example, system 100 may be configured to pick up, or attach, pipettes 116A, 116B, 116C to respective channels 114A, 114B, 1140. Additional pipettes 116A, 116B, 1160 may be stored within operational reach of the robotic gantry 112. In these aspects, system 100 may be capable of being reconfigured based on, e.g., a size of well plate 104, the number of wells 106 to be accessed on plate 104, etc. For example, during use, one or more ofAttorney Docket No. 00316-0041-00304 pipettes 116A, 116B, 116C may be replaced or removed from their respective channels 114A, 114B, 114C. Additionally or alternatively, pipettes 116A, 116B, 116C may be attached to other channels 114. In this respect, automated liquid handling gantries may be reprogrammed and reconfigured to function as described herein without needing to construct new hardware to achieve the novel methods and systems described herein. This advantageously saves money in hardware investments and time.

[0054] First pipette 116A may be a liquid handling pipette, or a fluidic pipette. Although a single liquid handling pipette (i.e. , first pipette 116A) is shown in FIGs. 2 and 4A-4C, multiple liquid handling pipettes may be utilized with system 100. For example, multiple liquid handling pipettes may be attached to multiple channels, e.g., if multiple wells 106 in well plate 104 are to be accessed at once. The additional liquid handling pipettes may have any or all of the same characteristics of first pipette 116A, as described below. For example, first pipette 116A may be fixed to an active channel 114A and may be configured to aspirate or inject a fluid. In these aspects, first pipette 116A may have a lumen 118 for aspirating or injecting the fluid. Lumen 118 is shown in broken lines, for example, to illustrate lumen 118 as being disposed within first pipette 116A. In some aspects, a portion of first pipette 116A may be tapered. For example, first pipette 116A may taper towards a point 120. Point 120 may include an opening 122 of lumen 118. First pipette 116A may be a piercing tip (e.g., a pipette having one or more fins or features to facilitate the creation of puncture openings) or may not be a piercing tip.

[0055] Second pipette 116B and third pipette 1160 shown in FIG. 2 may be referred to as teaching pipettes. In some aspects, second pipette 116B and / or third pipette 116C may be formed similarly to first pipette 116A. For example, secondAttorney Docket No. 00316-0041-00304 pipette 116B and / or third pipette 116C may include a lumen and / or taper towards a point 124. However, second pipette 116B and / or third pipette 116C may be configured to neither aspirate nor inject a fluid. In other aspects, second pipette 116B and / or third pipette 116C may be formed differently compared to first pipette 116A. For example, second pipette 116A and / or third pipette 116C may be a solid or hollow rod, as shown. Second pipette 116A and / or third pipette 116C may be pointed (as shown), rounded, flat, or blunted at an end oriented closest to well plate 104.

[0056] FIGs. 7A-7C illustrate alternative exemplary pipettes configured for use with system 100. For exemplary, the pipettes described in FIGs. 7A-7C may be used as second pipette 116A and / or third pipette 116C of FIGs. 2 and 4A-4D. For example, FIG. 7A illustrates an exemplary pipette 216 having a rounded tip 224. FIG. 7B illustrates an exemplary pipette 316 having a flat or blunted tip 324. FIG. 7C illustrates an exemplary pipette 416 having a “T” shaped tip 424. For example, tip 424 may extend in the Y- and / or X-directions (FIG. 2, 4A-4D), or may be crossshaped and may extend in both Y- and X-directions. Such a configuration of tip 424 may increase the contact surface area of tip 424 with well plate 104, for example, without covering one of the wells.

[0057] Referring back to FIG. 2, a length of second pipette 116A and third pipette 116C may be approximately equal to a length of first pipette 116A, although the length may also be different compared to a length of first pipette 116A.

[0058] Because second pipette 116B and third pipette 116C do not function to aspirate or inject fluid, they may each be attached to a channel that is inactive. Alternatively, they may be attached to active channels that are simply not used for the flow of fluid during processing of well plate 104.Attorney Docket No. 00316-0041-00304

[0059] First, second, and third pipettes may be formed of the same material or may be formed from different materials compared to one another. For example, they may be formed of metal, plastic, glass, or a combination thereof.

[0060] During use, first pipette 116A may be configured to puncture cover 105 to access at least one well 106. In these aspects, a user may not need to interact with cover 105, for example, to access the at least one well 106, and the remaining wells of well plate 104 may remain sealed or undisturbed. Further, a robotic system may not need to be developed to perform removal of cover 105, if the embodiments described herein are part of a larger, automated sample handling system. Second pipette 116B and third pipette 116C may be configured to maintain a position of well plate 104, particularly along the Z-axis. In some aspects, this may be achieved by exerting a downward pressure on the well plate 104, by touching the well plate 104 without exerting a downward pressure on the well plate 104, or by hovering just over the well plate 104, while the first pipette 116A is actuated. For example, second pipette 116B and third pipette 116C (and thus, second channel 114B and third channel 114C, respectively) may be positioned over ledge 110 (e.g., on one or both sides of well plate 104). In some aspects, a position of second pipette 116B and third pipette 116C on one or both sides of well plate 104 may be dictated, at least in part, by diameter A1 of channels 114. For example, third pipette 116C may be positioned over ledge 110 such that tip 124 of third pipette 116C contacts ledge 110 when / if well plate 104 lifts from stage 102. However, third channel 114C (coupled to third pipette 116C) may be positioned along gantry 112 such that first pipette 116A is still capable of accessing a well 106 arranged along the perimeter of plurality of wells 106. Accordingly, a smallest distance defined on the Y-axis, as measured between a center point of well 106 arranged along the perimeter of wellsAttorney Docket No. 00316-0041-00304106 and a center point of second channel 114B or third channel 114C may not be less than diameter A2 of channels 114. This may permit random access by first pipette 116A to wells 106. FIG. 3 illustrates a flow chart of an exemplary method 200. FIGs. 4A-4D illustrate system 100 of FIGs. 1 and 2 at various stages during use. FIG. 3 and FIGs. 4A-4D may be referred to interchangeably throughout the following description. In particular, FIGs. 4A-4D may be used to illustrate one or more steps of method 200.

[0061] In a first, optional step 202 of method 200, a user may input information, such as use parameters, into a software. The use parameters may include, for example, one or more dimensions or types of well plate 102, a volume of fluid to be aspirated from and / or injected into one or more wells of well plate 102, a speed and / or a distance at which pipettes 116A, 116B, 116C may travel in the Z- direction (whether the same or different), a speed at which gantry 112 may travel in the X-direction (or Y-direction, depending on orientation of gantry 112 relative to tray 104), a speed at which channels 114 may travel in the Y-direction (or X-direction, depending on orientation of gantry 112 relative to tray 104), identification of a specific well 106 or specific set of wells 106 to be used with method 200, etc. For example, a user may execute method 200 on one or more wells 106 of well plate 104.

[0062] In other aspects, step 202 may not need to be performed and may be omitted from method 200. For example, it may be that well plate 104 may have a unique identifier, such as a barcode, two-dimensional barcode (e.g., QR code, data matrix, etc.), etc., and well plate 104 may be scanned when it is positioned on stage 102. Information may be automatically conveyed to the controller of system 100 upon scanning of the identifier. In other aspects, the same parameters may apply toAttorney Docket No. 00316-0041-00304 all well plates 104 used in the system, and thus the parameters may be predetermined and may not change based on the individual well plate being processed according to method 200.

[0063] In a second step 204, the well plate 104 may be moved into position. In some aspects, a user may move well plate 104 into position, for example, on stage 102. In other aspects, e.g., in an automated system, well plate 104 may be moved into position by one or more other robotic components, and a user may not be needed to perform step 204. In this step, stage 102 may receive well plate 104.

[0064] In a third step 206, pipettes 116A, 116B, 116C may travel to a position over well plate 104, as shown in FIG. 4A. In this step, gantry 112 may be positioned over a first column of wells 106 of well plate 104. In particular, first pipette 116A may travel to a position over a well of the plurality of wells 106. Each of second pipette 116B and third pipette 116C may travel to a position over ledge 110, for example, on either side of well plate 104. Second pipette 116B may be positioned over a portion of ledge 110 at a first end of the column of wells 106 over which gantry 112 is positioned, and third pipette 116C may be positioned over a portion of ledge 110 at a second end of the column of wells 106 over which gantry 112 is positioned. Accordingly, second pipette 116B and third pipette 116C may be positioned over opposed ends of a column of wells 106, and first pipette 116A may be positioned over a well in that column. While one first pipette 116A is depicted in the figures as being positioned over a well 106, multiple first pipettes 116A may be posited over multiple wells 106 in a column, and may perform the steps of method 200 at substantially the same time, e.g., to decrease processing time. Further, although this description references the positioning of gantry 112 and pipettes 116 relative to columns, depending on the relative orientation of gantry 112 and well plateAttorney Docket No. 00316-0041-00304104, gantry 112 and pipettes 116 may alternatively be positioned over rows. Thus, for the purposes of this disclosure, columns and rows will be referred to interchangeably.

[0065] In a fourth step 208, one or more of pipettes 116A, 116B, 116C may travel down towards well plate 104. For example, one or more of pipettes 116A, 116B, 116C may travel in a Z-direction, toward well plate 104. In some aspects, pipettes 116A, 116B, 116C may travel in the Z-direction at different speeds, or they may travel at the same speed. In some instances, first pipette 116A may travel faster towards well plate 104 as compared to second pipette 116B and third pipette 116C, or vice versa.

[0066] In a fifth step 210, first pipette 116A may puncture cover 105 of well plate 104, as shown in FIG. 4B. For example, first pipette 116A may travel a greater distance in the Z-direction towards well plate 104 compared to second pipette 116B and third pipette 116C, such that first pipette 116A travels through cover 105 and at least partially into well 106, while second pipette 116B and third pipette 116C stop just above ledge 110 or contact ledge 110, without breaking a plane of cover 105. In some aspects, first pipette 116A may travel in the Z-direction at a faster speed than second pipette 116B and third pipette 116C so as to facilitate puncturing of cover105, although in other aspects, pipettes 116A, 116B, 116C may travel at the same speed. Second pipette 116B and third pipette 116C may travel a lesser distance in the Z-direction such that, for example, respective points 124 of each of second pipette 116B and third pipette 116C are touching, or abutting, ledge 110, or such that respective points 124 are positioned just above ledge 110 of well plate 104. In other words, respective points 124 of second pipette 116B and third pipette 116C may not touch or abut ledge 110 in fifth step 210. For example, second pipette 116B and thirdAttorney Docket No. 00316-0041-00304 pipette 116C may stop about approximately 0.5 cm or less away from ledge 110, e.g., approximately 0.4 cm or less, approximately 0.3 cm or less, approximately 0.2 cm or less, approximately 0.1 cm or less, approximately 0.5 cm, approximately 0.4 cm, approximately 0.3 cm, approximately 0.2 cm, approximately 0.1 cm, from 0 cm to approximately 0.5 cm, from approximately 0.1 cm to approximately 0.5 cm, approximately 0.1 cm to approximately 0.4 cm, approximately 0.2 cm to approximately 0.4 cm, etc. In some aspects, having second pipette 116B and third pipette 116C stop just shy of ledge 110 and not contact ledge 110 when moving downward in a Z-direction may inhibit wear and tear on pipettes 116B, 116C.

[0067] In some aspects, first pipette 116A, second pipette 116B, and third pipette 116C may move simultaneously in a Z-direction, while in other aspects, second pipette 116B and third pipette 116C may move together before or after first pipette 116A. In still other aspects, the three pipettes 116 may move downwards one after another.

[0068] In an optional sixth step 212, first pipette 116A may aspirate a fluid contained within well 106 and / or inject a fluid into well 106.

[0069] In a seventh step 214, first pipette 116A may travel upward, for example, away from well plate 104. In other words, first pipette 116A may travel in a Z-direction, away from well plate 104, as illustrated in FIG. 40. With first pipette 116A raised above well plate 104, an opening 130 may be defined in cover 105. In some aspects, for example, due to the tapered portion of first pipette 116A, the distance that first pipette 116A travels in the Z-direction into well 106 may determine a diameter, or width, of an opening 130 of cover 130. A maximum diameter of opening 130 may be approximately equal to a maximum diameter of first pipette 116A.Attorney Docket No. 00316-0041-00304

[0070] As first pipette 116A moves in a Z-direction away from well plate 104, second pipette 116B and third pipette 116C may remain in pace either touching or hovering above ledge 110. As first pipette moves in a Z-direction, there may be friction between cover 105, which was just pierced by first pipette 116A, and first pipette 116A. In some aspects, e.g., if fluid was aspirated out of the well 106 by first pipette 116A, a vacuum may be created within well 106. The friction between first pipette 116A withdrawing from well 106 and cover 105, or the vacuum created within well 106, may ordinarily cause well plate 104 to lift up with first pipette 116A off of stage 102. The presence of second pipette 116B and third pipette 116C hovering above or contacting ledge 110 may inhibit well plate 104 from lifting off stage 102, or from moving too far away from stage 102, as first pipette 116A travels upward, relative to well plate 104. For example, as first pipette 116A translates away from well plate 104, a frictional force may be generated between a surface of first pipette 116A and cover 105. The frictional force may result in well plate 104 lifting from stage 102, e.g., without the use of second pipette 116B and third pipette 116C. Accordingly, second pipette 116B and third pipette 116C may inhibit splashing or spillage of the contents of well 106 by inhibiting movement of well plate 104 in the Z- direction.

[0071] In some aspects, steps 206-214 may be repeated one or more times. Repetition of steps 206-214 may result in opening 130 being widened, or becoming elongated. For example, when step 206 is repeated after step 214, pipette 116A may translate in the X-direction to a new position above well plate 104. The new position may be slightly offset from the first position, but first pipette 116A may still be located over the same well 106 on well plate 104. When step 208 is repeated, pipette 116A may travel in the Z-direction, towards well plate 104, as discussed above, but in theAttorney Docket No. 00316-0041-00304 new X-position. When step 208 is repeated, first pipette 116A may, once again, puncture cover 105 of well plate 104. The additional puncture of cover 105 may be offset from the previous puncture of cover 105. For example, the additional puncture may be within a same well 106, and, in some aspects, may at least partially overlap with the previous (or initial) puncture of cover 105 or may be adjacent to the initial puncture. Accordingly, opening 130 may be elongated and / or a second opening may be generated within the same well 106.

[0072] In some aspects, optional step 212 of aspirating fluid within well 106 may not be performed during the first puncture, and may be instead performed during a subsequent puncture of the same well 106. The additional subsequent puncture may prevent a vacuum from being created within well 106 when optional step 212 (e.g., aspiration and / or injection of the fluid within well 106) is executed. Additionally or alternatively, the additional puncture may decrease an area of cover 105 that comes in contact with first pipette 116A, thereby assisting in decreasing a frictional force between first pipette 116A and cover 105. Decreasing a frictional force between first pipette 116A and cover 105 may also assist in preventing well plate 104 from being lifted off of stage 102.

[0073] In some aspects, a plurality (e.g., two, three, or more) of non-puncture steps 210, 214 may be performed before an aspirating step 212 is performed. For example, a first opening 130 may be made with a first puncture of first pipette 116A through cover 105, and then a second puncture with first pipette 116A located above, below, or laterally adjacent to the first puncture may enlarge first opening 103. In some aspects, a third puncture may subsequently be made on an opposite side of first opening 103 from the second puncture to further enlarge the first opening 103. Or, the first, second, and third punctures may be made sequentially in a sameAttorney Docket No. 00316-0041-00304 direction (e.g., above the first puncture and then above the second puncture). Additional, e.g., fourth or more punctures, may also be made to even further enlarge first opening 103. In some aspects, after first pipette 116A is moved downward one, two, three, or more times to puncture cover 105 and create a plurality of openings 103, or an enlarged opening 103, first pipette 116A may then enter well 106 in order to aspirate some or all of the contents of well 106, or to inject fluid (as in step 212, described above).

[0074] In some aspects, if one or more punctures are made (steps 206-210) before fluid is aspirated or injected (step 212), pipette 116A may travel towards well plate 104 in a Z-direction (step 208) a shorter distance during the puncture step 210, as compared to the aspiration step 212. For example, when puncturing cover 105, first pipette 116A may move downward towards well plate 104 in a Z-direction far enough to puncture cover 105, but shallow enough so as to stop moving in a Z- direction above the contents of well 106 so as to not disturb the contents of well 106. When moving towards well plate 104 in a Z-direction to aspirate fluid within well 106, first pipette 116A may move downward towards well plate 104 in a Z-direction far enough to stop moving in a Z-direction below a surface of the contents of well 106 and above the bottom of well 106. Thus, when aspirating or injecting fluid from or within well 106, an end tip of first pipette 116A may be submerged in the contents of well 106. In other aspects, for example, if step 212 includes injection of a fluid into well 106, or in embodiments in which cover 105 may only be punctured and step 212 may not be performed, first pipette 116A may travel in a Z-direction towards well plate 104 during step 206 a same distance each time.

[0075] While only one first pipette 116A is shown in the figures for simplification, a plurality of first pipettes 116A may be included on gantry 112, suchAttorney Docket No. 00316-0041-00304 that a plurality of wells 106 are accessed at the same time, each by a respective first pipette 116A. In some aspects, the relative positions of first pipettes 116A may be adjustable or may be fixed relative to one another.

[0076] In an eighth step 216, second pipette 116B and third pipette 116C may travel in a Z-direction upwards, away from well plate 104, as shown in FIG. 4D, after first pipette 116A has traveled away from well plate 104. Second pipette 116B and third pipette 116C may travel upwards, in the Z-direction, for example at a same or different speed as compared to first pipette 116A. Although FIG. 3 depicts the option of performing step 206 after step 214, in some aspects, step 216 may also occur prior to step 206, such that the arrow in FIG. 3 may extend from step 216 to step 206. In this way, second and third pipettes 116B, 116C may also travel upwards, in a Z-direction, prior to repositioning of the pipettes over well plate 102. In some aspects, steps 206-216 may be repeated two or more times, for example, to access two or more wells 106 of well plate 104, as described above in reference to the repetition of the steps 206-214. For example, instead of just first pipette 116A travelling away from well plate 114 (step 216) and then back towards well plate 114 (step 208), pipettes 116A, 116B, and 116C may all travel away from well plate 104 and then back down towards plate 104 repeatedly. In some aspects, each of pipettes 116A, 116B, and 116C may reposition over well plate 104 (step 206), or second pipettes 116B, 1160, respectively, may remain in a same position over ledge 110 of well plate 104, and only first pipette 116A is repositioned to a new position over well plate 104.

[0077] In a final step 218, well plate 104 may be removed from stage 102. In some aspects, removal of well plate 104 may be performed automatically by one or more components within a larger robotic system, or may be performed by a user,Attorney Docket No. 00316-0041-00304 such as a laboratory technician. Method 200 may be repeated, for example, with a new well plate 104.

[0078] Referring now to FIG. 5, an exemplary system environment 500 for executing the methods and processes described herein is provided. System environment 500 may include a control system 52, a controller 54, and a robotic gantry 56 (e.g., of the type described in this disclosure). Control system 52 may correspond to a central unit responsible for managing and coordinating the overall operation of the robotic gantry 56 and its associated components. In some aspects, the control system 52 may act as the main interface for users or operators, allowing them to input commands, set parameters, and monitor the status of the system. Control system 52 may process these commands and generate specific instructions that are then sent to controller 54. Control system 52 may include software that runs on a computer or a dedicated hardware unit.

[0079] The movements of the robotic gantry 56 may be governed by a controller 54. In the context of this application, a controller 54 may refer to any electronic device that manages the movement of the robotic gantry 56, e.g., by processing input signals (e.g., from an associated computer or control system 52), executing controlling algorithms, and sending output signals to drive one or more actuators and / or motors associated with the robotic gantry 56. By monitoring and adjusting based on the received instructions, the controller 54 ensures precise and coordinated movements of the robotic gantry 56 for various tasks.

[0080] In an aspect, the controller 54 may be integrally or operatively coupled to the robotic gantry 56 and may receive input signals and / or transmit output signals using wired or wireless means. For example, in a wired setup, input signals may be transmitted through physical cables, such as Ethernet or serial cables,Attorney Docket No. 00316-0041-00304 connecting the computer or control system 52 to the controller 54 and / or the controller 54 to one or more motors or actuators of the robotic gantry 56. In a wireless setup, input may be transmitted via wireless communication technologies, such as Wi-Fi , Bluetooth, or radio frequency (RF),

[0081] In general, any process discussed in this disclosure that is understood to be computer-implementable may be performed by one or more processors of a computer system, such as system environment 500, as described above. A process or process step performed by one or more processors may also be referred to as an operation. The one or more processors may be configured to perform such processes by having access to instructions (e.g., software or computer-readable code) that, when executed by the one or more processors, cause the one or more processors to perform the processes. The instructions may be stored in a memory of the computer server. A processor may be a central processing unit (CPU), a graphics processing unit (GPU), or any suitable types of processing unit.

[0082] A computer system, such as system environment 500, may include one or more computing devices. If the one or more processors of the computer system are implemented as a plurality of processors, the plurality of processors may be included in a single computing device or distributed among a plurality of computing devices. If a system environment comprises a plurality of computing devices, the memory of the computer system may include the respective memory of each computing device of the plurality of computing devices.

[0083] FIG. 6 is a simplified functional block diagram of a computer system 600 that may be configured as a computing device for executing the processes described herein, according to exemplary embodiments of the present disclosure. InAttorney Docket No. 00316-0041-00304 various embodiments, any of the systems herein may be an assembly of hardware including, for example, a data communication interface 620 for packet data communication. The platform also may include a central processing unit (“CPU”) 602, in the form of one or more processors, for executing program instructions. The platform may include an internal communication bus 608, and a storage unit 606 (such as ROM, HDD, SDD, etc.) that may store data on a computer readable medium 622, although the system 600 may receive programming and data via network communications via electronic network 625 (e.g., voice, video, audio, images, or any other data over the electronic network 625). The system 600 may also have a memory 604 (such as RAM) storing instructions 624 for executing techniques presented herein, although the instructions 624 may be stored temporarily or permanently within other modules of system 600 (e.g., processor 602 and / or computer readable medium 622). The system 600 also may include input and output ports 612 and / or a display 610 to connect with input and output devices such as keyboards, mice, touchscreens, monitors, displays, etc. The various system functions may be implemented in a distributed fashion on a number of similar platforms, to distribute the processing load. Alternatively, the systems may be implemented by appropriate programming of one computer hardware platform.

[0084] Program aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of executable code and / or associated data that is carried on or embodied in a type of machine-readable medium. “Storage” type media include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non-transitory storage at any time for the software programming. All or portions ofAttorney Docket No. 00316-0041-00304 the software may at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer of the mobile communication network into the computer platform of a server and / or from a server to the mobile device. Thus, another type of media that may bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links, or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

[0085] It should be appreciated that in the above description of exemplary embodiments, various features of the embodiments are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that a claimed embodiment requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the Detailed Description are hereby expressly incorporated into this Detailed Description, with each claim standing on its own as a separate embodiment.Attorney Docket No. 00316-0041-00304

[0086] Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the present disclosure, and form different embodiments, as would be understood by those skilled in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

[0087] Furthermore, some of the embodiments are described herein as a method or combination of elements of a method that can be implemented by a processor of a computer system or by other means of carrying out the function. Thus, a processor with the necessary instructions for carrying out such a method or element of a method forms a means for carrying out the method or element of a method. Furthermore, an element described herein of an apparatus embodiment is an example of a means for carrying out the function performed by the element for the purpose of carrying out the function.

[0088] In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the present disclosure may be practiced without these specific details. In other instances, well-known methods, structures, and techniques have not been shown in detail in order not to obscure an understanding of this description.

[0089] Similarly, it is to be noticed that the term coupled, when used in the claims, should not be interpreted as being limited to direct connections only. Thus, the scope of the expression a device A coupled to a device B should not be limited to devices or systems wherein an output of device A is directly connected to an input of device B. It means that there exists a path between an output of A and an input of B which may be a path including other devices or means. "Coupled" may mean thatAttorney Docket No. 00316-0041-00304 two or more elements are either in direct physical or electrical contact, or that two or more elements are not in direct contact with each other but yet still co-operate or interact with each other.

[0090] Thus, while there has been described what are believed to be the preferred embodiments of the present disclosure, those skilled in the art will recognize that other and further modifications may be made thereto without departing from the spirit of the present disclosure, and it is intended to claim all such changes and modifications as falling within the scope of the present disclosure. For example, any formulas given above are merely representative of procedures that may be used. Functionality may be added or deleted from the block diagrams and operations may be interchanged among functional blocks. Steps may be added or deleted to methods described within the scope of the present disclosure.

[0091] The above disclosed subject matter is to be considered illustrative, and not restrictive, and the appended claims are intended to cover all such modifications, enhancements, and other implementations, which fall within the true spirit and scope of the present disclosure. Thus, to the maximum extent allowed by law, the scope of the present disclosure is to be determined by the broadest permissible interpretation of the following claims and their equivalents, and shall not be restricted or limited by the foregoing detailed description. While various implementations of the disclosure have been described, it will be apparent to those of ordinary skill in the art that many more implementations and implementations are possible within the scope of the disclosure. Accordingly, the disclosure is not to be restricted except in light of the attached claims and their equivalents.

Claims

Attorney Docket No. 00316-0041-00304WHAT IS CLAIMED IS:1 . A robotic system, comprising: a movable gantry having a plurality of channels, wherein the plurality of channels includes at least a first channel, a second channel, and a third channel, wherein at least some of the plurality of channels are movable relative to one another along a length of the gantry, wherein a first device is fixed or is configured to be fixed to the first channel, a second device is fixed or is configured to be fixed to the second channel, and a third device is fixed or is configured to be fixed to the third channel; a stage above which the gantry is configured to move, wherein the stage is configured to receive a well plate having (i) a plurality of wells, (ii) an outer ledge that does not contain any wells, and (iii) a cover at least partially covering the plurality of wells; and one or more computer readable media storing instructions that are executable by one or more processors, wherein the one or more processors are operably coupled to a controller associated with the gantry, and when the well plate is received on the stage, cause the controller to perform operations to: in a first configuration: position the gantry over a first column of wells of the well plate, position the first device over a first well of the first column of wells, position the second device over a portion of the ledge at a first end of the first column of wells, andAttorney Docket No. 00316-0041-00304 position the third device over a portion of the ledge at a second end of the first column of wells; in a second configuration: move the first device, the second device, and the third device in a Z-direction towards the well plate, such that the first device punctures the cover of the well plate above the first well, and such that the second device and the third device either contact the ledge or are positioned above the ledge; and in a third configuration: move the first device in the Z-direction away from the well plate, while the second device and the third device remain in place to inhibit the well plate from lifting in the Z-direction with the first device.

2. The robotic system of claim 1 , wherein the first device is a pipette.

3. The robotic system of claim 1 , wherein, in the second configuration, the second device and the third device are not in contact with the ledge and are positioned approximately 0.1 cm to approximately 0.5 cm above the ledge.

4. The robotic system of claim 1 , wherein the first well contains a liquid, and wherein the one or more computer readable media storing instructions that are executable by the one or more processors are further configured to cause the controller to perform operations to: in a fourth configuration:Attorney Docket No. 00316-0041-00304 reposition at least one of the gantry or the first device such that the first device is positioned in a different location over the first well, move the first device in the Z-direction towards the well plate such that the first device punctures the cover of the well plate above the first well, and move the first device in the Z-direction away from the well plate.

5. The robotic system of claim 4, wherein the fourth configuration is performed a plurality of times.

6. The robotic system of claim 4, wherein in the second configuration, the first device is moved in the Z-direction to a position within the first well above a surface of the liquid within the first well.

7. The robotic system of claim 6, wherein in the fourth configuration, the first device is moved in the Z-direction to a position within the first well below the surface of the liquid within the first well.

8. The robotic system of claim 4, wherein the fourth configuration is performed a plurality of times, and wherein all but a last time the fourth configuration is performed, the first device is moved in the Z-direction to a position within the first well above a surface of the liquid within the first well.

9. The robotic system of claim 8, wherein the last time the fourth configuration is performed, the first device is moved in the Z-direction to a positionAttorney Docket No. 00316-0041-00304 within the first well and below a surface of the liquid within the first well, and the liquid is aspirated by the device.

10. The robotic system of claim 4, wherein the fourth configuration is performed a plurality of times, and wherein the second device and the third device are moved in a Z-direction away from the well plate after the first device is moved in the Z-direction away from the well plate each time.11 . The robotic system of claim 4, wherein the one or more computer readable media storing instructions that are executable by the one or more processors are further configured to cause the controller to perform operations to: in a fifth configuration: move the second device and the third device in a Z-direction away from the well plate.

12. The robotic system of claim 1 , wherein the one or more computer readable media storing instructions that are executable by the one or more processors are further configured to cause the controller to perform operations in the second configuration to: cause the first device to inject a liquid into the first well after having been moved in the Z-direction towards the well plate.

13. The robotic system of claim 1 , wherein the one or more computer readable media storing instructions that are executable by the one or more processors are further configured to cause the controller to perform operations to:Attorney Docket No. 00316-0041-00304 in a fourth configuration: move the second device and the third device in a Z-direction away from the well plate.

14. A method comprising: receiving a well plate in an automated robotic system, wherein the well plate has (i) a plurality of wells, (ii) an outer ledge that does not contain any wells, and (iii) a cover at least partially covering the plurality of wells; positioning a gantry over a first column of wells of the well plate, wherein the gantry includes a pipette operably connected thereto, a first device, and a second device; positioning the pipette over a first well of the first column of wells; positioning the first device over a portion of the ledge at a first end of the first column of wells; positioning the second device over a portion of the ledge at a second end of the first column of wells; moving the pipette, the first device, and the second device in a Z-direction towards the well plate, such that the pipette punctures the cover of the well plate above the first well, and such that the first device and the second device either contact the ledge or are positioned above the ledge; and moving the pipette in the Z-direction away from the well plate, while the first device and the second device remain in place to inhibit the well plate from lifting in the Z-direction with the pipette.

15. The method of claim 14, further comprising:Attorney Docket No. 00316-0041-00304 transmitting, using one or more processors of the automated robotic system, one or more instructions to a controller that cause the controller to perform the positioning steps and the moving steps.

16. The method of claim 14, further comprising: moving the first device and the second device in the Z-direction away from the well plate.

17. The method of claim 14, further comprising: repositioning at least one of the gantry or the pipette such that the pipette is positioned in a different location over the first well; moving the pipette in the Z-direction towards the well plate such that the first device punctures the cover of the well plate above the first well; and moving the pipette in the Z-direction away from the well plate.

18. The method of claim 17, in which the repositioning step, the moving the pipette in the Z-direction towards the well plate step, and the moving the pipette in the Z-direction away from the well plate step are repeated multiple times either to form multiple openings in the cover above the well plate or to form a widened opening in the cover above the well plate, and wherein all but a last time the repeated steps are performed, the pipette is moved in the Z-direction towards the well plate to a position within the first well above a surface of the liquid within the first well, and wherein the last time the repeated steps are performed, the pipette is moved in the Z-direction towards the well plate to a position within the first well belowAttorney Docket No. 00316-0041-00304 the surface of the liquid within the first well and aspirates the liquid within the first well before moving the pipette in the Z-direction away from the well plate.

19. The method of claim 17, wherein each time the pipette is moved in the Z- direction away from the well plate, the first device and the second device remain in place to inhibit the well plate from lifting in the Z-direction with the pipette.

20. The method of claim 19, wherein each time the pipette is moved in the Z- direction away from the well plate, the first device and the second device subsequently move in the Z-direction away from the well plate, and the first device and the second device also move in the Z-direction towards the well plate when the pipette is moved in the Z-direction towards the well plate.21 . The method of claim 14, wherein the moving the first device and the second device in the Z-direction towards the well plate comprises positioning the first device and the second device approximately 0.1 cm to approximately 0.5 cm above the ledge.

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