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WO2025171185A1 - Inflatable sleeve pipette system and apparatus - Google Patents

Inflatable sleeve pipette system and apparatus

Info

Publication number
WO2025171185A1
WO2025171185A1 PCT/US2025/014871 US2025014871W WO2025171185A1 WO 2025171185 A1 WO2025171185 A1 WO 2025171185A1 US 2025014871 W US2025014871 W US 2025014871W WO 2025171185 A1 WO2025171185 A1 WO 2025171185A1
Authority
WO
WIPO (PCT)
Prior art keywords
pipette
fluid
sleeve
inflatable
manifold
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/014871
Other languages
French (fr)
Inventor
Maximilian SCHOMMER
Hannah Dearman SO
Talia WIDGER
Itzel HERNANDEZ
Allison TSAI
Gabriel ZWILLINGER
Cole NAGATA
Marina RING
Dalton LAZAROBY
Angie LEE
Scott Mackinlay
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Trilobio Inc
Original Assignee
Trilobio Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Trilobio Inc filed Critical Trilobio Inc
Publication of WO2025171185A1 publication Critical patent/WO2025171185A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065Multiple transfer devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/103General features of the devices using disposable tips

Definitions

  • aspects of the present disclosure relate to biological processing systems and apparatuses, for example, pipette apparatuses.
  • Biological laboratory processing requires many distinct processes to be performed on a variety of samples. These processes include transferring samples from one place to another, pipetting samples, covering samples with protective lids, and many others. Additionally, it is desirable to avoid spillage and cross-contamination of samples.
  • Pipettes can be useful tools for completing biological protocols because they can transfer precise volumes of fluid to carry out experiments. Many biological protocols can be conducted across many samples in parallel — in these cases, a pipette with multiple channels, called a multichannel pipette, can be used.
  • pipettes do not contaminate the fluid they are moving. As a result, pipettes typically use sterile disposable tips that are changed regularly in order to prevent undesired contamination. Ideally, pipettes should form an airtight seal with a pipette tip so that they can displace liquid accurately. If there is a leak between the pipette and the pipette tip, aspiration and dispensing functions may be lower than typical. To form this seal, most pipettes use a conical manifold designed to fit inside a conical tip. By applying a sufficient force along the length of the pipette tip, the cone of the tip is forced onto the cone of the pipette manifold. As the pipette tip expands slightly from the force, the airtight seal can be formed.
  • a conical manifold and conical tip can cause severe issues when used for a plurality of channels such as, for example, 96 or more channels.
  • the axial force that forms the airtight seal typically can be in the range of about 4 N to IO N per tip. Therefore, for a 96-channel pipette, such force would scale to about 384 N to about 960 N of force, which is high enough to crush most boxes of pipette tips.
  • many robots which can fit in a biology lab are not capable of producing forces nearly that high. For example, such robots in a biology lab setting typically can have a load rating of about 5 kg to about 10 kg, or about 50 N to about 100 N.
  • the cone mating method may cause an unevenness of force distribution over the different channels. Since the existing method of forming seals is based on the mating of cones, it is very sensitive to slight variations in the distance of the pipette manifold to the pipette tip. As a result, this sensitivity makes it extremely difficult to form reliable seals with all 96 channels.
  • FIGS. 1A and IB illustrate perspective views of a biological processing system, according to some aspects.
  • FIGS. 2A-2G illustrate cross-section views of pipette apparatuses, according to some aspects.
  • FIG. 3 illustrates a cross-section view of an ejection apparatus, according to some aspects.
  • FIG. 4 illustrates a method of using a pipette apparatus in a biological processing system, according to some aspects.
  • FIGS. 1A and IB illustrate perspective views of a biological processing system, referred to as system 100, according to some aspects.
  • System 100 can perform a particular function such as, for example, a pipetting process.
  • System 100 can include tools and devices to accomplish its function.
  • system 100 can include a robot arm 102, a pipette apparatus 104, a reservoir 106, and a sleeve pump 108.
  • system 100 can further include one or more sensors 110 and a controller 112.
  • robot arm 102 can be coupled to a chassis, such as an overhead support structure.
  • Robot arm 102 can be an articulable manipulator capable of movement in some or all directions. This configuration can allow robot arm 102 to move along a platform deck containing objects (e.g., biological samples) and access each object. Robot arm 102 can then move in a vertical direction (i.e., towards and away from the chassis) via an extension and retraction system internal to robot arm 102. In this way, robot arm 102 can reach any location on or within the volume of the chassis.
  • objects e.g., biological samples
  • the chassis may have a cuboid shape (e.g., cube, rectangular prism, trapezoidal prism, or the like) having a volume, such as a deck with an overhead and/or side support structure as described in PCT Appl. Publ. WO 2023/173038, which is incorporated by reference herein in its entirety.
  • a cuboid shape e.g., cube, rectangular prism, trapezoidal prism, or the like
  • a volume such as a deck with an overhead and/or side support structure as described in PCT Appl. Publ. WO 2023/173038, which is incorporated by reference herein in its entirety.
  • one or more modular tools may be located on (e.g., mounted to), within the volume of, or near the chassis supporting robot arm 102.
  • the chassis supporting robot arm 102 may contain a tool storage support containing tools not currently in use by robot arm 102.
  • robot arm 102 can be equipped with an electromagnetic tool changer as described in PCT Appl. Publ. WO 2024/220551, which is incorporated by reference herein in its entirety.
  • the electromagnetic tool changer can enable robot arm 102 to interact with modular tools located on, within the volume of, or near the chassis supporting robot arm 102.
  • robot arm 102 can place, insert, or otherwise connect the electromagnetic tool changer to a modular tool, in order to secure the modular tool.
  • robot arm 102 can be configured to remove and replace one of the modular tools from the chassis (e.g., from the tool storage support located thereon) with the use of the electromagnetic tool changer. Therefore, robot arm 102 can be configured to move a modular tool to a location on or within a biological processing environment.
  • each of the one or more pipette tips 114 can be sized and shaped to store up to about 20 pL of fluid. In some aspects, each of the one or more pipette tips 114 can be sized and shaped to store up to about 1 mL of fluid. In aspects in which the one or more pipette tips 114 is a plurality of pipette tips, the plurality of pipette tips can be arranged in an array of rows and columns. For example, in the example aspect shown in FIGS. 1 A and IB, the plurality of pipette tips can be arranged in an 8x12 array.
  • the multichannel pipette device can be time- and labor-efficient for laboratory experiments dealing with repetitive transfers of multiple volumes of fluid.
  • the multichannel pipette device of pipette apparatus 104 can have 96 pipette manifolds arranged in an array that matches the array of pipette tips 114.
  • the 96 pipette manifolds can be arranged in an 8x12 array.
  • a skilled artisan will recognize that other pipette manifold and tip sizes and shapes may instead be used.
  • robot arm 102 can be configured to move pipette apparatus 104 toward the one or more pipette tips 114. Once pipette apparatus 104 is inserted into pipette tips 114, pipette apparatus 104 can use one or more inflatable sleeves to pick up the one or more pipette tips 114. As a result, robot arm 102 may not apply any axial force to the one or more pipette tips 114. Therefore, in some aspects, robot arm 102 can insert or otherwise position pipette apparatus 104 into pipette tips 114 without applying an axial force to pipette tips 114 along the Z-axis (i.e., a zero-magnitude force).
  • robot arm 102 can apply a low-magnitude axial actuation force 116 to pipette tips 114 along a Z-axis parallel to a length of each one of pipette tips 114.
  • force 116 can be a magnitude of less than approximately 50 N.
  • robot arm 102 can be configured to apply a substantially equal distribution of force 116 across each of the one or more pipette tips 114.
  • pipette apparatus 104 can be configured to pick up and/or release one or more pipette tips 114.
  • pipette apparatus 104 can use one or more inflatable sleeves (described below with respect to FIGS. 2A-G) disposed on corresponding ones of pipette manifolds of pipette apparatus 104.
  • the inflatable sleeves located around the outer surfaces of the pipette manifolds can be inflated until they press against the corresponding inner surfaces of the pipette tips.
  • the friction created by the inflatable sleeve pressing against the inner surface of the pipette tip secures the pipette tip to its corresponding pipette manifold. With such a connection, little to no Z-axis force between the pipette manifold and the corresponding pipette tip is needed.
  • the sleeve can remain inflated as long as the pipette tip is in use. When the pipette tip is to be discarded or otherwise removed, the inflatable sleeve around the outer surface of the corresponding pipette manifold can be deflated, thus releasing the pipette tip.
  • the one or more inflatable sleeves can be in fluid communication via one or more fluid channels to operate based on hydraulics or pneumatics. All of the one or more fluid channels can be connected fluidically to be actuated by a sleeve pump 108. Accordingly, the one or more inflatable sleeves can be configured to inflate and secure the one or more pipette tips 114 to pipette apparatus 104 and/or to deflate and release the one or more pipette tips 114 to pipette apparatus 104. In some aspects, multiple sleeve pumps 108 fluidically connected to one or a subset of inflatable sleeves via one or more fluid channels may be used to inflate one or some inflatable sleeves independently of other inflatable sleeves.
  • pipette apparatus 104 can be configured to move fluid through the one or more pipette tips 114.
  • pipette apparatus 104 can be used to accurately aspirate and dispense predetermined volumes of fluid such as, for example, liquid solutions, biological samples, cell cultures, chemical solutions, or the like.
  • Aspiration is the process of collecting fluid into the one or more pipette tips 114.
  • Dispensing is the process of releasing fluid out of the one or more pipette tips 114.
  • pipette apparatus 104 can use a mechanical force or one or more electric motors such as, for example, actuators 105, to aspirate and/or dispense fluid.
  • actuators 105 can be configured to drive one or more pistons of one or more sample channel pumps to create a pressure differential that moves a sample in a given direction through a corresponding one of pipette tips 114.
  • Actuators 105 can be mounted anywhere on pipette apparatus 104 that enables aspiration and dispensing action.
  • actuators 105 can be mounted on pipette apparatus 104 with fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like. In the example aspect shown in FIGS. 1 A and IB, actuators 105 can be mounted on the sides of pipette apparatus 104.
  • reservoir 106 can be configured to store a fluid 118.
  • reservoir 106 can be a container configured to store fluid 118.
  • Reservoir 106 can be located anywhere within or near system 100 that enables pipette apparatus 104 to receive fluid 118.
  • reservoir 106 can be located on, within the volume of, or near the chassis supporting robot arm 102.
  • reservoir 106 can be located remotely from the chassis supporting robot arm 102 but in fluid communication with pipette apparatus 104 through one or more channels such as tubing. In the example aspect shown in FIGS.
  • reservoir 106 can be mounted on pipette apparatus 104 with fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like.
  • fluid 118 can be a non-reactive fluid that does not interact with a sample in the event of a possible leak.
  • fluid 118 can be a non-biologically reactive fluid.
  • fluid 118 can be a liquid such as, for example, water or the like.
  • fluid 118 can be a gas such as, for example, air or the like.
  • sleeve pump 108 can be coupled to reservoir 106 and the one or more fluid channels of pipette apparatus 104.
  • sleeve pump 108 can be coupled to reservoir 106 and the one or more fluid channels of pipette apparatus 104 via a tubing 120.
  • Sleeve pump 108 can be located anywhere within or near system 100 that enables pipette apparatus 104 to receive fluid 118.
  • sleeve pump 108 can be located on, within the volume of, or near the chassis supporting robot arm 102.
  • sleeve pump 108 can be located remotely from the chassis supporting robot arm 102 but in fluid communication with pipette apparatus 104 through one or more channels such as tubing.
  • sleeve pump 108 can be mounted on pipette apparatus 104 with fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like.
  • fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like.
  • system 100 can be equipped with a plurality of reservoirs 106 and/or sleeve pumps 108 such that each of the reservoirs 106 and/or sleeve pumps 108 can be coupled to corresponding ones of or subsets of the one or more fluid channels of pipette apparatus 104.
  • sleeve pump 108 can be configured to supply fluid 118 from reservoir 106 to the one or more inflatable sleeves of pipette apparatus 104 via the one or more fluid channels.
  • sleeve pump 108 can be a two-way pump configured to supply and withdraw fluid 118 at each of the one or more fluid channels.
  • sleeve pump 108 can be a one-way pump configured to supply the fluid to each of the one or more fluid channels.
  • the one or more fluid channels and/or the pipette apparatus 104 can be fitted with a release valve to allow fluid to flow in the opposite direction from the pumped direction.
  • sleeve pump 108 can be a hydraulic pump. In aspects in which fluid 118 is a gas, sleeve pump 108 can be a pneumatic pump.
  • system 100 can be equipped with a plurality of sleeve pumps 108 to ensure stable and consistent flow of fluid 118 through all or selected ones of the one or more fluid channels of pipette apparatus 104.
  • sensor 110 can be coupled to some or each of the one or more inflatable sleeves of pipette apparatus 104.
  • sensor 110 includes a plurality of sensors.
  • Sensor 110 can be configured to detect at least one of a pressure or volume of fluid 118 in some or each of the one or more inflatable sleeves of pipette apparatus 104.
  • controller 112 can be coupled to sensor 110 and sleeve pump 108. Controller 112 can be configured to send a signal to sleeve pump 108 to adjust an amount of fluid 118 in all, some, or each of the one or more inflatable sleeves of pipette apparatus 104. The signal to adjust can be based on at least one of the pressure or volume of fluid 118 detected by sensor 110. In some aspects, controller 112 may be controlled by instructions transmitted from a central processing system, as described in PCT Appl. Publ. WO 2023/173038, which is incorporated by reference herein in its entirety.
  • system 100 can offer numerous advantages for biological processing procedures.
  • pipette apparatus 104 can pick up and eject one or more pipette tips 114 reliably.
  • system 100 can pick up all 96 pipette tips 114 with over 99% reliability and can eject all 96 pipette tips 114 with over 99% reliability by respectively inflating and deflating the inflatable sleeve between each pipette manifold and its corresponding pipette tip.
  • pipette apparatus 104 also can aspirate about 1 pL to about 20 pL of fluid across all 96 pipette tips 114 with a coefficient of variance of less than about 5%.
  • system 100 can perform thousands of experiment cycles reliably without components wearing down.
  • system 100 can be inexpensive to repair and maintain.
  • system 100 can be less expensive to manufacture than present commercial systems.
  • pipette apparatus 104 can be sized and shaped such that pipette apparatus 104 does not interfere with other use cases of robot arm 102.
  • FIGS. 2A-2G illustrate cross-section views of a pipette apparatus 203 and pipette apparatus 204, according to some aspects.
  • FIGS. 2A-F illustrate example aspects of pipette apparatus 203 that can include a single pipette device having a single pipette manifold configured to interact with a single pipette tip.
  • FIG. 2G illustrates an example aspect of pipette apparatus 204 that can include a multichannel pipette device having an array of pipette manifolds configured to interact with corresponding ones of pipette tips arranged in an array.
  • pipette apparatus 204 as shown in FIG. 2G can be a cross-section of pipette apparatus 104 as shown in FIGS. 1A and IB.
  • pipette apparatus 204 can include a plurality of pipette apparatuses 203 arranged in an array.
  • FIG. 2 A illustrates a cross-section view of a pipette apparatus 203, according to some aspects.
  • pipette apparatus 203 can be a single pipette device configured to interact with a pipette tip 214.
  • pipette apparatus 203 can include a pipette manifold 222, a sample channel 224, a sample channel pump 226, an inflatable sleeve 228, and a fluid channel 230.
  • sample channel 224 can be disposed within pipette manifold 222.
  • Sample channel 224 can be called an “aspiration and dispensing channel.”
  • sample channel 224 can be configured to carry air or the like.
  • sample channel pump 226 can be coupled to the sample channel 224.
  • Sample channel pump 226 can be configured to create a pressure differential that moves a sample in a given direction through the pipette tip 214.
  • inflatable sleeve 228 can be disposed over and/or around the pipette manifold 222.
  • Inflatable sleeve 228 can be made from a flexible material such as, for example, at least one of an elastic material, a rubber material, or a latex material.
  • Inflatable sleeve 228 can be configured to deform and stretch within certain parameters without breaking.
  • fluid channel 230 can be configured to carry fluid 118. Accordingly, fluid channel 230 can form at least a portion of a fluidic path between reservoir 106 and inflatable sleeve 228.
  • fluid channel 230 can be disposed within pipette manifold 222.
  • fluid channel 230 can be disposed adjacent to sample channel 224 within pipette manifold 222 and fluid channel 230 can have an outlet 231 disposed on a surface of pipette manifold 222 inside inflatable sleeve 228.
  • fluid channel 230 can be disposed outside of pipette manifold 222.
  • fluid channel 230 can be disposed adjacent to pipette manifold 222 and can be directly connected to inflatable sleeve 228.
  • FIG. 2B illustrates a cross-section view of pipette manifold 222 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2B shows inflatable sleeve 228 in a deflated state 236 in which there is no or little fluid present in inflatable sleeve 228.
  • inflatable sleeve 228 can be sealed to pipette manifold 222 by at least one of an adhesive material 232 or a compression device 234.
  • adhesive material 232 can be at least one of a sealing fluid, a glue, an epoxy, an oil, a grease, or the like.
  • compression device 234 can be one or more of a compression fitting (as represented by compression device 234a), a retention fitting (as represented by compression device 234b), or a retention screw (as represented by compression device 234c), or the like.
  • Adhering and/or mechanically fixing inflatable sleeve 228 to pipette manifold 222 can prevent leaks of fluid.
  • compression fitting of compression device 234a can be mechanically attached to manifold base 223 of pipette manifold 222 using fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like.
  • Compression fitting of compression device 234a can provide compression to inflatable sleeve 228 in order to prevent leaks near the manifold base 223.
  • compression devices 234a-234c also can prevent the inflatable sleeve 228 from rubbing against pipette tip 214 during insertion and ejection. In this manner, compression devices 234a-234c can prevent unwanted wear on inflatable sleeve 228.
  • compression devices 234a-234c also can enable alignment of pipette tip 214 with pipette manifold 222.
  • robot arm 102 can move pipette apparatus 203 toward pipette tip 214 such that pipette manifold 222 inserts into pipette tip 214.
  • Sleeve pump 108 can be set to a low or no pressure so that inflatable sleeve 228 remains in deflated state 236 and does not rub against pipette tip 214 during the insertion process.
  • sensor 210 can detect at least one of a pressure or volume of fluid in inflatable sleeve 228.
  • controller 212 can compare the detected value of a pressure or volume against a threshold value to determine whether pressure or volume is too high in inflatable sleeve 228 for the insertion process. In response to the comparison, controller 212 can send a signal to sleeve pump 108 to reduce an amount of fluid in inflatable sleeve 228, thereby establishing deflated state 236.
  • FIG. 2C illustrates a cross-section view of pipette manifold 222 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2C shows inflatable sleeve 228 in an inflated state 238 in which fluid 218 is present in inflatable sleeve 228.
  • inflatable sleeve 228 can be configured to fill with fluid 218 supplied from fluid channel 230 to secure pipette manifold 222 to pipette tip 214 when pipette manifold 222 is inserted into pipette tip 214.
  • inflatable sleeve 228 can receive fluid 218 from outlet 231 of fluid channel 230.
  • Sleeve pump 108 can increase a pressure or volume of fluid 218 in fluid channel 230 to inflate inflatable sleeve 228. As inflatable sleeve 228 inflates, inflatable sleeve 228 can come into contact with pipette tip 214.
  • inflatable sleeve 228 can be configured to secure pipette manifold 222 to pipette tip 214 via static friction.
  • a seal can be formed between inflatable sleeve 228 and pipette tip 214.
  • the seal can be airtight such that air does not escape from or enter into pipette tip 214.
  • sensor 210 can detect at least one of a pressure or volume of fluid 218 in inflatable sleeve 228.
  • controller 212 can compare the detected value of a pressure or volume against a threshold value to determine whether pressure or volume is too low in inflatable sleeve 228 for a pipette tip securing process. In response to the comparison, controller 212 can send a signal to sleeve pump 108 to increase an amount of fluid in inflatable sleeve 228, thereby establishing inflated state 238.
  • robot arm 102 can move pipette apparatus 203 holding pipette tip 214 to a target area and can insert pipette tip 214 into a sample for transfer.
  • FIG. 2D illustrates a cross-section view of pipette manifold 222 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2D shows inflatable sleeve 228 in an inflated state 238 in which fluid 218 is present in inflatable sleeve 228 without being inserted into a corresponding pipette tip.
  • inflatable sleeve 228 can be fitted with a stop 240.
  • Stop 240 can be located at a distance around the inflatable sleeve.
  • stop 240 can be sized, shaped, and positioned to prevent inflatable sleeve 228 from expanding beyond a given point when no pipette tip is present.
  • stop 240 can be a barrier that is configured to be fastened to pipette apparatus 203 adjacent to and around pipette manifold 222 and inflatable sleeve 228.
  • Stop 240 can be positioned at a distance from pipette manifold 222 and inflatable sleeve 228 that allows a wall of a pipette tip, such as pipette tip 214, to be inserted between inflatable sleeve 228 and stop 240.
  • FIG. 2E illustrates a cross-section view of sample channel pump 226 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2E shows sample channel pump 226 performing an aspiration process of a sample 242.
  • sample channel pump 226 can be coupled to sample channel 224.
  • Sample channel pump 226 can be configured to create a pressure differential that moves a sample in a given direction through pipette tip 214.
  • the pressure differential can move sample 242 into pipette tip 214 in aspiration direction 244.
  • sample channel pump 226 can include a pressure chamber 246, a piston 252, and a sealing apparatus 254.
  • pressure chamber 246 can be a hollow cavity disposed within pipette apparatus 203.
  • Pressure chamber 246 can include a first end 248 coupled to the sample channel 224 and a second end 250.
  • Pressure chamber 246 can be configured to hold piston 252 and a volume of air or the like.
  • piston 252 can be disposed within pressure chamber 246. Piston 252 can be configured to create, through movement of piston 252 relative to pressure chamber 246 and the chamber walls created by pipette apparatus 203, the pressure differential that moves sample 242 in the given direction through pipette tip 214.
  • sealing apparatus 254 can be disposed at second end 250 of pressure chamber 246. Sealing apparatus 254 can secure piston 252 to pressure chamber 246. In some aspects, sealing apparatus 254 can be a mechanical seal such as, for example, an O-ring. A skilled artisan would recognize that sealing apparatus 254 can alternatively be placed on an end of piston 252 within pressure chamber 246 near first end 248.
  • FIG. 2F illustrates a cross-section view of sample channel pump 226 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2F shows sample channel pump 226 performing a dispensing process of a sample.
  • sample channel pump 226 can be configured to create a pressure differential that moves a sample in a given direction through the pipette tip 214.
  • the pressure differential can move sample 242 out from pipette tip 214 in dispensing direction 245.
  • robot arm 102 can move pipette apparatus 203 to a target area while pipette tip 214 carries sample 242.
  • an actuator 105 can move piston 252 to push out sample 242 from pipette tip 214.
  • piston 252 can move in dispensing direction 245 to decrease a volume of air present in pressure chamber 246.
  • a pressure of the air increases and sample 242 can flow out from pipette tip 214 in dispensing direction 245.
  • robot arm 102 can use pipette apparatus 203 to dispense sample 242 at a target area within the biological processing environment.
  • FIG. 2G illustrates a cross-section view of a pipette apparatus 204, according to some aspects.
  • pipette apparatus 204 can be a multichannel pipette device having an array of pipette manifolds 222 configured to interact with corresponding ones of pipette tips 214 arranged in an array.
  • pipette apparatus 204 as shown in FIG. 2G can be a cross-section of pipette apparatus 104 as shown in FIGS. 1 A and IB.
  • pipette apparatus 204 can be a cross-section of pipette apparatus 104
  • pipette apparatus 204 is depicted as a cross-section of a row of 8 pipette apparatuses 203. Accordingly, the discussion of components of pipette apparatus 203 described with reference to FIGS. 2A-2F applies to the discussion of components of pipette apparatus 204 and reference numerals are not repeated on FIG. 2G for clarity.
  • pipette apparatus 204 can include one or more pipette manifolds 222, one or more sample channels 224, one or more sample channel pumps 226, one or more inflatable sleeves 228, and one or more fluid channels 230 (depicted by reference to pipette apparatuses 203, shown in FIGS. 2A-F).
  • each of the one or more pipette manifolds 222 can be sized and shaped to receive a corresponding pipette tip 214.
  • each of the one or more sample channels 224 can be disposed within a corresponding one of the one or more pipette manifolds 222.
  • one or more sample channel pumps 226 can be coupled to the one or more sample channels 224.
  • the one or more sample channel pumps 226 can be configured to create a pressure differential that moves a sample 242 in a given direction through the corresponding pipette tip 214.
  • at least one of the one or more sample channel pumps 226 can include a pressure chamber 246, a piston 252, and a sealing apparatus 254.
  • pressure chamber 246 can include a first end 248 coupled to a corresponding one of the one or more sample channels 224 and a second end 250.
  • piston 252 can be disposed within pressure chamber 246.
  • each of the one or more inflatable sleeves 228 can be disposed over a corresponding one of the one or more pipette manifolds 222.
  • Each of the one or more inflatable sleeves 228 can be made from a flexible material.
  • each of the one or more inflatable sleeves 228 can be individual components.
  • each of the one or more inflatable sleeves 228 can be protrusions from a continuous overlay component that fits across all of pipette manifolds 222.
  • each of the one or more inflatable sleeves 228 is sealed to a corresponding one of the one or more pipette manifolds 222 by at least one of an adhesive material 232 or a compression device 234.
  • each of the one or more inflatable sleeves 228 is configured to fill with fluid 218 supplied from the one or more fluid channels 230 to secure the corresponding one of the one or more pipette manifolds 222 to the corresponding pipette tip 214 when the corresponding one of the one or more pipette manifolds 222 is inserted into the corresponding pipette tip 214. Accordingly, each of the one or more inflatable sleeves 228 is configured to secure the corresponding one of the one or more pipette manifolds 222 to the corresponding pipette tip 214 via static friction.
  • each of one or more stops 240 can be located at a distance around corresponding ones of the one or more inflatable sleeves 228.
  • Each stop 240 can be sized, shaped, and positioned to prevent the corresponding inflatable sleeve 228 from expanding beyond a given point when no pipette tip is present.
  • each of the sample channel pumps 226 can be coupled to a corresponding one of the one or more sample channels 224.
  • each of the one or more fluid channels 230 forms at least a portion of a fluidic path between reservoir 106 and a corresponding one of the one or more inflatable sleeves 228.
  • sleeve pump 108 can be configured to supply fluid 118 from reservoir 106 to each of the one or more inflatable sleeves 228 via a corresponding one of the one or more fluid channels 230.
  • Pipette tip 214 may be ejected via gravity or an ejection apparatus.
  • FIG. 3 illustrates a cross-section view of an ejection apparatus 356 on pipette apparatus 304, according to some aspects.
  • pipette apparatus 304 can be a multichannel pipette device having a plurality of pipette manifolds 322.
  • pipette apparatus 304 as shown in FIG. 3 can be a cross-section of pipette apparatus 104 as shown in FIGS. 1A and IB.
  • ejection apparatus 356 can also be used with a single-pipette device such as, for example, pipette apparatus 203 as shown in and described with reference to FIGS. 2A-2F.
  • ejection apparatus 356 can be mounted anywhere on pipette apparatus 304 that enables ejection of pipette tips 314.
  • ejection apparatus 356 can be mounted on pipette apparatus 304 with fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like.
  • ejection apparatus 356 can be mounted inside pipette apparatus 304. While FIG. 3 shows a crosssection of ejection apparatus 356, a skilled artisan would understand that ejection apparatus 356 can be a single plate that surrounds multiple or all of pipette manifolds 322. Alternatively, each pipette manifold 322 may be fitted with its own independent ejection apparatus 356.
  • ejection apparatus 356 can be configured to eject pipette tips 314 disposed on corresponding ones of pipette manifolds 322.
  • Ejection apparatus 356 can have an ejector surface 359.
  • ejection apparatus 356 can be positioned at a location where ejector surface 359 would not contact pipette tips 314.
  • actuators 105 can move ejection apparatus 356 in ejection direction 357.
  • actuators 105 can continue moving ejector surface 359 in ejection direction 357 until pipette tips 314 separate from the corresponding pipette manifolds 322.
  • ejector surface 359 can be a substantially uniform surface that ejects most or all pipette tips 314 at once.
  • ejector surface 359 can have a stairstep surface to eject a few pipette tips 314 at a time as ejector surface 359 moves further in the ejection direction 357 to minimize ejection forces.
  • ejector surface 359 can be higher in the middle of the apparatus than on the edges.
  • actuator 105 can move ejection apparatus 356 opposite to ejection direction 357 to return ejection apparatus 356 to its rest state.
  • ejection apparatus 356 can include a spring-loaded mechanism 358.
  • Spring-loaded mechanism 358 can be secured in place relative to pipette apparatus 104 and configured to have a rest state that keeps ejector surface 359 away from pipette tips 314.
  • spring-loaded mechanism 358 is compressed.
  • the spring- loaded mechanism 358 can return to its uncompressed state, causing ejection surface 359 to move in a direction opposite to direction 357 and reset back to the rest state.
  • the movement of ejection apparatus 356 is independent of the movement of pistons 252. In other aspects, the movement of ejection apparatus 356 is coupled to the movement of pistons 252. In such aspects, the distance in direction 357 traveled by ejection apparatus 356 in order to eject pipette tips 314 can be a further extension of a distance traveled when pistons 252 perform a dispensing action.
  • robot arm 102 can use pipette apparatus 304 to dispense a sample at a target area within the biological processing environment. Once the pipette tips 314 are empty, the pipette tips 314 can be ready for disposal.
  • Actuators 105 can move ejection surface 359 in the ejection direction 357 to eject pipette tips 314 from the corresponding ones of pipette manifolds 322. In this configuration, system 100 can use ejection apparatus 356 to dispose of pipette tips 314 that have been used and/or contaminated.
  • FIG. 4 illustrates a method 460 of using a pipette apparatus (e.g., pipette apparatus 203 as shown in and described with reference to FIGS. 2A-2F) in a biological processing system (e.g., system 100 as shown in and described with reference to FIGS. 1A and IB), according to some aspects.
  • a pipette apparatus e.g., pipette apparatus 203 as shown in and described with reference to FIGS. 2A-2F
  • a biological processing system e.g., system 100 as shown in and described with reference to FIGS. 1A and IB
  • a pipette manifold e.g., pipette manifold 222 as shown in and described with reference to FIGS. 2A-2F
  • a pipette tip e.g., pipette manifold 214 as shown in and described with reference to FIGS. 2A-2F
  • the pipette manifold can have an inflatable sleeve (e.g., inflatable sleeve 228 as shown in and described with reference to FIGS. 2A-2F) disposed thereon.
  • a fluid e.g., fluid 118 as shown in and described with reference to FIGS. 1A and IB
  • a reservoir e.g., reservoir 106 as shown in and described with reference to FIGS. 1 A and IB
  • a pump e.g., sleeve pump 108 as shown in and described with reference to FIGS. 1 A and IB
  • a fluid channel e.g., fluid channel 230 as shown in and described with reference to FIGS. 2A-2F
  • the inflatable sleeve can be filled with an amount of fluid via the fluid channel.
  • the pipette manifold can be secured to the pipette tip via static friction created by the filling.
  • method 460 can further include moving a piston (e.g., piston 252 as shown in and described with reference to FIGS. 2E-2F) in a first direction (e.g., aspiration direction 244 as shown in and described with reference to FIG. 2E) to aspirate a sample (e.g., sample 242 as shown in and described with reference to FIGS. 2E-2F) into the pipette tip, the piston disposed within a pressure chamber (e.g., pressure chamber 246 as shown in and described with reference to FIGS. 2E-2F) coupled to the sample channel.
  • a piston e.g., piston 252 as shown in and described with reference to FIGS. 2E-2F
  • a first direction e.g., aspiration direction 244 as shown in and described with reference to FIG. 2E
  • a sample e.g., sample 242 as shown in and described with reference to FIGS. 2E-2F
  • a pressure chamber e.g., pressure chamber 246 as shown in and
  • method 460 can further include moving the piston in a second direction (e.g., dispensing direction 245 as shown in and described with reference to FIG. 2F) to dispense the sample from the pipette tip.
  • a second direction e.g., dispensing direction 245 as shown in and described with reference to FIG. 2F
  • method 460 can further include deflating the inflatable sleeve by removing fluid from the inflatable sleeve via the fluid channel.
  • the fluid may be removed by reversing a pumping direction of the pump (e.g., when the pump is a two-way pump) or by releasing a valve to change the pressure acting on the fluid (e.g., when the pump is a one-way pump).
  • method 460 can further include ejecting the pipette tip from the pipette manifold by activating a spring-loaded mechanism of an ejection apparatus (e.g., ejection apparatus 356 as shown in and described with reference to FIG. 3) coupled to the pipette manifold.
  • an ejection apparatus e.g., ejection apparatus 356 as shown in and described with reference to FIG. 3
  • the pipette manifold can be a plurality of pipette manifolds, each pipette manifold having a corresponding inflatable sleeve.
  • the fluid channel can be a plurality of fluid channels each disposed in fluid communication with a corresponding inflatable sleeve.
  • the inserting comprises inserting each pipette manifold in the plurality of pipette manifolds into a corresponding pipette tip in a plurality of pipette tips.
  • the supplying comprises supplying, with the pump, the fluid stored in the reservoir to the plurality of fluid channels.
  • the filling comprises filling each inflatable sleeve with the amount of fluid via the corresponding fluid channel in the plurality of fluid channels.
  • the securing comprises securing the each pipette manifold in the plurality of pipette manifolds to the corresponding pipette tip in the plurality of pipette tips via the static friction created by the filling.
  • the method steps of FIG. 4 can be performed in any reasonable order and it is not required that all steps be performed. Moreover, the method steps of FIG. 4 described above merely reflect an example of steps and are not limiting. That is, further method steps and functions are envisaged based on aspects described in reference to FIGS. 1A-3.

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Abstract

An example system includes a fluid reservoir, a robot arm, a pipette apparatus, and a sleeve pump. The pipette apparatus is coupled to the robot arm and includes a pipette manifold, a sample channel, a sample channel pump, an inflatable sleeve, and a fluid channel. The sample channel pump is coupled to the sample channel and creates a pressure differential that moves a sample in a given direction through a pipette tip disposed on the pipette manifold. The inflatable sleeve is disposed over the pipette manifold. The sleeve pump supplies the fluid from the reservoir to the inflatable sleeve via the fluid channel. When inflated, the inflatable sleeve secures a pipette tip to the pipette manifold.

Description

INFLATABLE SLEEVE PIPETTE SYSTEM AND APPARATUS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The following application claims the benefit of U.S. Provisional Appl. No. 63/550,197, filed February 6, 2024, which is incorporated herein by reference in its entirety.
BACKGROUND
FIELD
[0002] Aspects of the present disclosure relate to biological processing systems and apparatuses, for example, pipette apparatuses.
BACKGROUND
[0003] Biological laboratory processing requires many distinct processes to be performed on a variety of samples. These processes include transferring samples from one place to another, pipetting samples, covering samples with protective lids, and many others. Additionally, it is desirable to avoid spillage and cross-contamination of samples.
[0004] Pipettes can be useful tools for completing biological protocols because they can transfer precise volumes of fluid to carry out experiments. Many biological protocols can be conducted across many samples in parallel — in these cases, a pipette with multiple channels, called a multichannel pipette, can be used.
[0005] It is important that pipettes do not contaminate the fluid they are moving. As a result, pipettes typically use sterile disposable tips that are changed regularly in order to prevent undesired contamination. Ideally, pipettes should form an airtight seal with a pipette tip so that they can displace liquid accurately. If there is a leak between the pipette and the pipette tip, aspiration and dispensing functions may be lower than typical. To form this seal, most pipettes use a conical manifold designed to fit inside a conical tip. By applying a sufficient force along the length of the pipette tip, the cone of the tip is forced onto the cone of the pipette manifold. As the pipette tip expands slightly from the force, the airtight seal can be formed.
[0006] However, the use of a conical manifold and conical tip can cause severe issues when used for a plurality of channels such as, for example, 96 or more channels. The axial force that forms the airtight seal typically can be in the range of about 4 N to IO N per tip. Therefore, for a 96-channel pipette, such force would scale to about 384 N to about 960 N of force, which is high enough to crush most boxes of pipette tips. Additionally, many robots which can fit in a biology lab are not capable of producing forces nearly that high. For example, such robots in a biology lab setting typically can have a load rating of about 5 kg to about 10 kg, or about 50 N to about 100 N.
[0007] In addition to the issue of extremely high forces, the cone mating method may cause an unevenness of force distribution over the different channels. Since the existing method of forming seals is based on the mating of cones, it is very sensitive to slight variations in the distance of the pipette manifold to the pipette tip. As a result, this sensitivity makes it extremely difficult to form reliable seals with all 96 channels.
[0008] Lastly, because of the high force supplied to secure the pipette tip to the manifold, it is difficult to remove the tip after its use is complete.
[0009] Therefore, existing pipette apparatuses neither use the proper amount of force nor the proper distribution of force to interact with pipette tips via a highly dynamic robot arm. In addition, many of the existing pipette apparatuses are too heavy, too complex, and too expensive for mass market production.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The accompanying drawings, which are incorporated herein and form part of the specification, illustrate the present disclosure and, together with the description, further serve to explain the principles of the present disclosure and to enable those skilled in the relevant art(s) to make and use aspects described herein.
[0011] FIGS. 1A and IB illustrate perspective views of a biological processing system, according to some aspects.
[0012] FIGS. 2A-2G illustrate cross-section views of pipette apparatuses, according to some aspects.
[0013] FIG. 3 illustrates a cross-section view of an ejection apparatus, according to some aspects.
[0014] FIG. 4 illustrates a method of using a pipette apparatus in a biological processing system, according to some aspects. DETAILED DESCRIPTION
[0015] This specification discloses one or more aspects that incorporate various features of this present invention. The disclosed aspect(s) merely exemplify the present invention. The scope of the invention is not limited to the disclosed aspect(s). The present invention is defined by the claims appended hereto.
[0016] The aspect(s) described, and references in the specification to “one aspect,” “an aspect,” “an example aspect,” “an exemplary aspect,” etc., indicate that the aspect(s) described may include a particular feature, structure, or characteristic, but every aspect may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same aspect. Further, when a particular feature, structure, or characteristic is described in connection with an aspect, it is understood that it is within the knowledge of one skilled in the art to effect such feature, structure, or characteristic in connection with other aspects whether or not explicitly described.
[0017] Spatially relative terms, such as “beneath,” “below,” “lower,” “above,” “on,” “upper” and the like, may be used herein for ease of description to describe one element or feature’s relationship to another element(s) or feature(s) as illustrated in the figures. The spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. The apparatus may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein may likewise be interpreted accordingly.
[0018] The term “about” or “substantially” or “approximately” as used herein indicates the value of a given quantity that can vary based on a particular technology. Based on the particular technology, the term “about” or “substantially” or “approximately” can indicate a value of a given quantity that varies within, for example, 1-15% of the value (e.g., ±1%, ±2%, ±5%, ±10%, or ±15% of the value).
Example Biological Processing System
[0019] Provided herein are system, apparatus, device, and/or method, and/or combinations and sub-combinations thereof, for a biological processing laboratory assembly that performs pipetting processes within or across modular robotic systems.
[0020] FIGS. 1A and IB illustrate perspective views of a biological processing system, referred to as system 100, according to some aspects. System 100 can perform a particular function such as, for example, a pipetting process. System 100 can include tools and devices to accomplish its function. In some aspects, system 100 can include a robot arm 102, a pipette apparatus 104, a reservoir 106, and a sleeve pump 108. In some aspects, system 100 can further include one or more sensors 110 and a controller 112.
[0021] In some aspects, robot arm 102 can be coupled to a chassis, such as an overhead support structure. Robot arm 102 can be an articulable manipulator capable of movement in some or all directions. This configuration can allow robot arm 102 to move along a platform deck containing objects (e.g., biological samples) and access each object. Robot arm 102 can then move in a vertical direction (i.e., towards and away from the chassis) via an extension and retraction system internal to robot arm 102. In this way, robot arm 102 can reach any location on or within the volume of the chassis. In some aspects, the chassis may have a cuboid shape (e.g., cube, rectangular prism, trapezoidal prism, or the like) having a volume, such as a deck with an overhead and/or side support structure as described in PCT Appl. Publ. WO 2023/173038, which is incorporated by reference herein in its entirety.
[0022] In some aspects, one or more modular tools may be located on (e.g., mounted to), within the volume of, or near the chassis supporting robot arm 102. For example, the chassis supporting robot arm 102 may contain a tool storage support containing tools not currently in use by robot arm 102. In some aspects, robot arm 102 can be equipped with an electromagnetic tool changer as described in PCT Appl. Publ. WO 2024/220551, which is incorporated by reference herein in its entirety. The electromagnetic tool changer can enable robot arm 102 to interact with modular tools located on, within the volume of, or near the chassis supporting robot arm 102. For example, robot arm 102 can place, insert, or otherwise connect the electromagnetic tool changer to a modular tool, in order to secure the modular tool. In some aspects, robot arm 102 can be configured to remove and replace one of the modular tools from the chassis (e.g., from the tool storage support located thereon) with the use of the electromagnetic tool changer. Therefore, robot arm 102 can be configured to move a modular tool to a location on or within a biological processing environment.
[0023] In the example aspect shown in FIGS. 1 A and IB, robot arm 102 can be coupled to and interact with a modular tool such as, for example, pipette apparatus 104. In some aspects, pipette apparatus 104 can be operated within an entire range of motion of robot arm 102 such as, for example, located on, within the volume of, or near the chassis supporting robot arm 102 or located on, within the volume of, or near an adjacent chassis supporting another robot arm 102. For example, pipette apparatus 104 can interact with objects located on, within the volume of, or near the chassis supporting robot arm 102 or located on, within the volume of, or near an adjacent chassis supporting another robot arm 102. These objects can include, for example, pipette tips, sample plates, test tubes, or the like. In some aspects, pipette apparatus 104 can receive command signals from robot arm 102 for interaction with objects in a biological processing environment, such as described in PCT Appl. Publ. WO 2023/173038, which is incorporated by reference herein in its entirety. For example, pipette apparatus 104 can communicate with robot arm 102 via a Controller Area Network (CAN) bus or a Controller Area Network Flexible Data-Rate (CAN FD) bus.
[0024] In some aspects, pipette apparatus 104 can be configured to interact with one or more pipette tips 114. The one or more pipette tips 114 can be located on, within the volume of, or near the chassis supporting robot arm 102. In some aspects, one or more pipette tips 114 can be a vessel for storing, aspirating, and/or dispensing predetermined volumes of fluid such as, for example, liquid solutions, biological samples, cell cultures, chemical solutions, or the like. The one or more pipette tips 114 can be a disposable attachment for pipette apparatus 104. The one or more pipette tips 114 can be made from a plastic material. In some aspects, each of the one or more pipette tips 114 can be sized and shaped to store up to about 20 pL of fluid. In some aspects, each of the one or more pipette tips 114 can be sized and shaped to store up to about 1 mL of fluid. In aspects in which the one or more pipette tips 114 is a plurality of pipette tips, the plurality of pipette tips can be arranged in an array of rows and columns. For example, in the example aspect shown in FIGS. 1 A and IB, the plurality of pipette tips can be arranged in an 8x12 array.
[0025] In some aspects, pipette apparatus 104 can include a single pipette device having a single pipette manifold configured to interact with a single one of pipette tips 114. In some aspects, pipette apparatus 104 can include a multichannel pipette device having an array of any number of pipette manifolds configured to interact with corresponding ones of pipette tips 114 arranged in an array. The multichannel pipette device can attach to multiple ones of pipette tips 114 and thus can transfer multiple volumes of fluid simultaneously. In this configuration, sample interactions can be run in parallel, which may be more efficient than the use of a single pipette device interacting with samples individually. Accordingly, the multichannel pipette device can be time- and labor-efficient for laboratory experiments dealing with repetitive transfers of multiple volumes of fluid. In some aspects, as shown in the example aspect of FIGS. 1A and IB, the multichannel pipette device of pipette apparatus 104 can have 96 pipette manifolds arranged in an array that matches the array of pipette tips 114. For example, the 96 pipette manifolds can be arranged in an 8x12 array. A skilled artisan will recognize that other pipette manifold and tip sizes and shapes may instead be used.
[0026] In some aspects, robot arm 102 can be configured to move pipette apparatus 104 toward the one or more pipette tips 114. Once pipette apparatus 104 is inserted into pipette tips 114, pipette apparatus 104 can use one or more inflatable sleeves to pick up the one or more pipette tips 114. As a result, robot arm 102 may not apply any axial force to the one or more pipette tips 114. Therefore, in some aspects, robot arm 102 can insert or otherwise position pipette apparatus 104 into pipette tips 114 without applying an axial force to pipette tips 114 along the Z-axis (i.e., a zero-magnitude force). A skilled artisan would recognize that there may be circumstances in which a small amount of force is still used to secure pipette tips 114 to pipette apparatus 104. Therefore, in some aspects, robot arm 102 can apply a low-magnitude axial actuation force 116 to pipette tips 114 along a Z-axis parallel to a length of each one of pipette tips 114. For example, force 116 can be a magnitude of less than approximately 50 N. In aspects in which pipette apparatus 104 includes a multichannel pipette device, robot arm 102 can be configured to apply a substantially equal distribution of force 116 across each of the one or more pipette tips 114.
[0027] In some aspects, pipette apparatus 104 can be configured to pick up and/or release one or more pipette tips 114. For example, pipette apparatus 104 can use one or more inflatable sleeves (described below with respect to FIGS. 2A-G) disposed on corresponding ones of pipette manifolds of pipette apparatus 104. When the pipette manifolds of pipette apparatus 104 are inserted into corresponding pipette tips 114, the inflatable sleeves located around the outer surfaces of the pipette manifolds can be inflated until they press against the corresponding inner surfaces of the pipette tips. The friction created by the inflatable sleeve pressing against the inner surface of the pipette tip secures the pipette tip to its corresponding pipette manifold. With such a connection, little to no Z-axis force between the pipette manifold and the corresponding pipette tip is needed. The sleeve can remain inflated as long as the pipette tip is in use. When the pipette tip is to be discarded or otherwise removed, the inflatable sleeve around the outer surface of the corresponding pipette manifold can be deflated, thus releasing the pipette tip.
[0028] The one or more inflatable sleeves can be in fluid communication via one or more fluid channels to operate based on hydraulics or pneumatics. All of the one or more fluid channels can be connected fluidically to be actuated by a sleeve pump 108. Accordingly, the one or more inflatable sleeves can be configured to inflate and secure the one or more pipette tips 114 to pipette apparatus 104 and/or to deflate and release the one or more pipette tips 114 to pipette apparatus 104. In some aspects, multiple sleeve pumps 108 fluidically connected to one or a subset of inflatable sleeves via one or more fluid channels may be used to inflate one or some inflatable sleeves independently of other inflatable sleeves.
[0029] In some aspects, pipette apparatus 104 can be configured to move fluid through the one or more pipette tips 114. For example, pipette apparatus 104 can be used to accurately aspirate and dispense predetermined volumes of fluid such as, for example, liquid solutions, biological samples, cell cultures, chemical solutions, or the like. Aspiration is the process of collecting fluid into the one or more pipette tips 114. Dispensing is the process of releasing fluid out of the one or more pipette tips 114. In some aspects, pipette apparatus 104 can use a mechanical force or one or more electric motors such as, for example, actuators 105, to aspirate and/or dispense fluid.
[0030] In some aspects, actuators 105 can be configured to drive one or more pistons of one or more sample channel pumps to create a pressure differential that moves a sample in a given direction through a corresponding one of pipette tips 114. Actuators 105 can be mounted anywhere on pipette apparatus 104 that enables aspiration and dispensing action. In some aspects, actuators 105 can be mounted on pipette apparatus 104 with fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like. In the example aspect shown in FIGS. 1 A and IB, actuators 105 can be mounted on the sides of pipette apparatus 104.
[0031] In some aspects, reservoir 106 can be configured to store a fluid 118. For example, reservoir 106 can be a container configured to store fluid 118. Reservoir 106 can be located anywhere within or near system 100 that enables pipette apparatus 104 to receive fluid 118. For example, reservoir 106 can be located on, within the volume of, or near the chassis supporting robot arm 102. In another example, reservoir 106 can be located remotely from the chassis supporting robot arm 102 but in fluid communication with pipette apparatus 104 through one or more channels such as tubing. In the example aspect shown in FIGS. 1A and IB, reservoir 106 can be mounted on pipette apparatus 104 with fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like. In some aspects, fluid 118 can be a non-reactive fluid that does not interact with a sample in the event of a possible leak. When the sample is a biological sample, fluid 118 can be a non-biologically reactive fluid. In some aspects, fluid 118 can be a liquid such as, for example, water or the like. In some aspects, fluid 118 can be a gas such as, for example, air or the like.
[0032] In some aspects, sleeve pump 108 (see FIG. IB) can be coupled to reservoir 106 and the one or more fluid channels of pipette apparatus 104. For example, sleeve pump 108 can be coupled to reservoir 106 and the one or more fluid channels of pipette apparatus 104 via a tubing 120. Sleeve pump 108 can be located anywhere within or near system 100 that enables pipette apparatus 104 to receive fluid 118. For example, sleeve pump 108 can be located on, within the volume of, or near the chassis supporting robot arm 102. In another example, sleeve pump 108 can be located remotely from the chassis supporting robot arm 102 but in fluid communication with pipette apparatus 104 through one or more channels such as tubing. In the example aspect shown in FIG. IB, sleeve pump 108 can be mounted on pipette apparatus 104 with fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like. A skilled artisan would recognize that system 100 can be equipped with a plurality of reservoirs 106 and/or sleeve pumps 108 such that each of the reservoirs 106 and/or sleeve pumps 108 can be coupled to corresponding ones of or subsets of the one or more fluid channels of pipette apparatus 104.
[0033] In some aspects, sleeve pump 108 can be configured to supply fluid 118 from reservoir 106 to the one or more inflatable sleeves of pipette apparatus 104 via the one or more fluid channels. In some aspects, sleeve pump 108 can be a two-way pump configured to supply and withdraw fluid 118 at each of the one or more fluid channels. In some aspects, sleeve pump 108 can be a one-way pump configured to supply the fluid to each of the one or more fluid channels. In some aspects where sleeve pump 108 is a one-way pump, the one or more fluid channels and/or the pipette apparatus 104 can be fitted with a release valve to allow fluid to flow in the opposite direction from the pumped direction. In aspects in which fluid 118 is a liquid, sleeve pump 108 can be a hydraulic pump. In aspects in which fluid 118 is a gas, sleeve pump 108 can be a pneumatic pump. A skilled artisan would recognize that system 100 can be equipped with a plurality of sleeve pumps 108 to ensure stable and consistent flow of fluid 118 through all or selected ones of the one or more fluid channels of pipette apparatus 104.
[0034] In some aspects, sensor 110 can be coupled to some or each of the one or more inflatable sleeves of pipette apparatus 104. In some aspects, sensor 110 includes a plurality of sensors. Sensor 110 can be configured to detect at least one of a pressure or volume of fluid 118 in some or each of the one or more inflatable sleeves of pipette apparatus 104.
[0035] In some aspects, controller 112 can be coupled to sensor 110 and sleeve pump 108. Controller 112 can be configured to send a signal to sleeve pump 108 to adjust an amount of fluid 118 in all, some, or each of the one or more inflatable sleeves of pipette apparatus 104. The signal to adjust can be based on at least one of the pressure or volume of fluid 118 detected by sensor 110. In some aspects, controller 112 may be controlled by instructions transmitted from a central processing system, as described in PCT Appl. Publ. WO 2023/173038, which is incorporated by reference herein in its entirety.
[0036] In some aspects, in operation, system 100 can offer numerous advantages for biological processing procedures. First, pipette apparatus 104 can pick up and eject one or more pipette tips 114 reliably. In one example operation in which there are 9620 pL pipette tips 114 and pipette apparatus 104 contains 96 corresponding pipette manifolds, system 100 can pick up all 96 pipette tips 114 with over 99% reliability and can eject all 96 pipette tips 114 with over 99% reliability by respectively inflating and deflating the inflatable sleeve between each pipette manifold and its corresponding pipette tip. In this example operation, pipette apparatus 104 also can aspirate about 1 pL to about 20 pL of fluid across all 96 pipette tips 114 with a coefficient of variance of less than about 5%. Second, system 100 can perform thousands of experiment cycles reliably without components wearing down. Third, system 100 can be inexpensive to repair and maintain. Fourth, system 100 can be less expensive to manufacture than present commercial systems. Fifth, pipette apparatus 104 can be sized and shaped such that pipette apparatus 104 does not interfere with other use cases of robot arm 102.
[0037] FIGS. 2A-2G illustrate cross-section views of a pipette apparatus 203 and pipette apparatus 204, according to some aspects. FIGS. 2A-F illustrate example aspects of pipette apparatus 203 that can include a single pipette device having a single pipette manifold configured to interact with a single pipette tip. FIG. 2G illustrates an example aspect of pipette apparatus 204 that can include a multichannel pipette device having an array of pipette manifolds configured to interact with corresponding ones of pipette tips arranged in an array. In some aspects, pipette apparatus 204 as shown in FIG. 2G can be a cross-section of pipette apparatus 104 as shown in FIGS. 1A and IB. In some aspects, pipette apparatus 204 can include a plurality of pipette apparatuses 203 arranged in an array.
[0038] FIG. 2 A illustrates a cross-section view of a pipette apparatus 203, according to some aspects. In some aspects, pipette apparatus 203 can be a single pipette device configured to interact with a pipette tip 214. In some aspects, pipette apparatus 203 can include a pipette manifold 222, a sample channel 224, a sample channel pump 226, an inflatable sleeve 228, and a fluid channel 230.
[0039] In some aspects, pipette manifold 222 can be the main body of pipette apparatus 203. In some aspects, pipette manifold 222 can be sized and shaped to receive a pipette tip 214. For example, pipette manifold 222 can be inserted into pipette tip 214 by robot arm 102. Accordingly, pipette manifold 222 can be called a “tip holder.” Pipette manifold 222 can include one or more channels configured to carry fluid disposed along a length of pipette manifold 222.
[0040] In some aspects, sample channel 224 can be disposed within pipette manifold 222. Sample channel 224 can be called an “aspiration and dispensing channel.” In some aspects, sample channel 224 can be configured to carry air or the like.
[0041] In some aspects, sample channel pump 226 can be coupled to the sample channel 224. Sample channel pump 226 can be configured to create a pressure differential that moves a sample in a given direction through the pipette tip 214.
[0042] In some aspects, inflatable sleeve 228 can be disposed over and/or around the pipette manifold 222. Inflatable sleeve 228 can be made from a flexible material such as, for example, at least one of an elastic material, a rubber material, or a latex material. Inflatable sleeve 228 can be configured to deform and stretch within certain parameters without breaking.
[0043] In some aspects, fluid channel 230 can be configured to carry fluid 118. Accordingly, fluid channel 230 can form at least a portion of a fluidic path between reservoir 106 and inflatable sleeve 228. In some aspects, fluid channel 230 can be disposed within pipette manifold 222. For example, fluid channel 230 can be disposed adjacent to sample channel 224 within pipette manifold 222 and fluid channel 230 can have an outlet 231 disposed on a surface of pipette manifold 222 inside inflatable sleeve 228. In some aspects, fluid channel 230 can be disposed outside of pipette manifold 222. For example, fluid channel 230 can be disposed adjacent to pipette manifold 222 and can be directly connected to inflatable sleeve 228.
[0044] FIG. 2B illustrates a cross-section view of pipette manifold 222 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2B shows inflatable sleeve 228 in a deflated state 236 in which there is no or little fluid present in inflatable sleeve 228.
[0045] In some aspects, inflatable sleeve 228 can be sealed to pipette manifold 222 by at least one of an adhesive material 232 or a compression device 234. In some aspects, adhesive material 232 can be at least one of a sealing fluid, a glue, an epoxy, an oil, a grease, or the like. In some aspects, compression device 234 can be one or more of a compression fitting (as represented by compression device 234a), a retention fitting (as represented by compression device 234b), or a retention screw (as represented by compression device 234c), or the like. Adhering and/or mechanically fixing inflatable sleeve 228 to pipette manifold 222 can prevent leaks of fluid.
[0046] For example, in the example aspect shown in FIG. 2B, inflatable sleeve 228 can be sealed to a manifold tip 221 of pipette manifold 222 with adhesive material 232. In this example, the retention fitting of compression device 234b can apply compression to hold inflatable sleeve 228 against manifold tip 221. In this example, the retention screw of compression device 234c can secure compression device 234b in place to maintain a compressive fitting on inflatable sleeve 228 against manifold tip 221. Retention screw of compression device 234c can be fastened to manifold tip 221 via threads or clamping, for example. The combination of adhesive material 232 and compression devices 234b, 234c can prevent leaks near manifold tip 221. In this example, the compression fitting of compression device 234a can be mechanically attached to manifold base 223 of pipette manifold 222 using fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like. Compression fitting of compression device 234a can provide compression to inflatable sleeve 228 in order to prevent leaks near the manifold base 223. In some aspects, compression devices 234a-234c also can prevent the inflatable sleeve 228 from rubbing against pipette tip 214 during insertion and ejection. In this manner, compression devices 234a-234c can prevent unwanted wear on inflatable sleeve 228. In some aspects, compression devices 234a-234c also can enable alignment of pipette tip 214 with pipette manifold 222. [0047] In some aspects, in an example operation, robot arm 102 can move pipette apparatus 203 toward pipette tip 214 such that pipette manifold 222 inserts into pipette tip 214. Sleeve pump 108 can be set to a low or no pressure so that inflatable sleeve 228 remains in deflated state 236 and does not rub against pipette tip 214 during the insertion process. In some aspects, sensor 210 can detect at least one of a pressure or volume of fluid in inflatable sleeve 228. In some aspects, controller 212 can compare the detected value of a pressure or volume against a threshold value to determine whether pressure or volume is too high in inflatable sleeve 228 for the insertion process. In response to the comparison, controller 212 can send a signal to sleeve pump 108 to reduce an amount of fluid in inflatable sleeve 228, thereby establishing deflated state 236.
[0048] FIG. 2C illustrates a cross-section view of pipette manifold 222 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2C shows inflatable sleeve 228 in an inflated state 238 in which fluid 218 is present in inflatable sleeve 228.
[0049] In some aspects, inflatable sleeve 228 can be configured to fill with fluid 218 supplied from fluid channel 230 to secure pipette manifold 222 to pipette tip 214 when pipette manifold 222 is inserted into pipette tip 214. For example, inflatable sleeve 228 can receive fluid 218 from outlet 231 of fluid channel 230. Sleeve pump 108 can increase a pressure or volume of fluid 218 in fluid channel 230 to inflate inflatable sleeve 228. As inflatable sleeve 228 inflates, inflatable sleeve 228 can come into contact with pipette tip 214. Accordingly, in some aspects, inflatable sleeve 228 can be configured to secure pipette manifold 222 to pipette tip 214 via static friction. When the pressure of fluid 218 in inflatable sleeve 228 exceeds an atmospheric pressure around inflatable sleeve 228, a seal can be formed between inflatable sleeve 228 and pipette tip 214. For example, the seal can be airtight such that air does not escape from or enter into pipette tip 214.
[0050] In some aspects, in an example operation, sensor 210 can detect at least one of a pressure or volume of fluid 218 in inflatable sleeve 228. In some aspects, controller 212 can compare the detected value of a pressure or volume against a threshold value to determine whether pressure or volume is too low in inflatable sleeve 228 for a pipette tip securing process. In response to the comparison, controller 212 can send a signal to sleeve pump 108 to increase an amount of fluid in inflatable sleeve 228, thereby establishing inflated state 238. Once the threshold value is exceeded and pipette tip 214 is secured on pipette manifold 222, robot arm 102 can move pipette apparatus 203 holding pipette tip 214 to a target area and can insert pipette tip 214 into a sample for transfer.
[0051] FIG. 2D illustrates a cross-section view of pipette manifold 222 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2D shows inflatable sleeve 228 in an inflated state 238 in which fluid 218 is present in inflatable sleeve 228 without being inserted into a corresponding pipette tip.
[0052] In some aspects, inflatable sleeve 228 can be configured to support a maximum pressure or volume of fluid 218 without rupturing. In some aspects, inflatable sleeve 228 can be configured to support a maximum pressure or volume of fluid 218 without a pipette tip to secure.
[0053] In some aspects, inflatable sleeve 228 can be fitted with a stop 240. Stop 240 can be located at a distance around the inflatable sleeve. In some aspects, stop 240 can be sized, shaped, and positioned to prevent inflatable sleeve 228 from expanding beyond a given point when no pipette tip is present. For example, stop 240 can be a barrier that is configured to be fastened to pipette apparatus 203 adjacent to and around pipette manifold 222 and inflatable sleeve 228. Stop 240 can be positioned at a distance from pipette manifold 222 and inflatable sleeve 228 that allows a wall of a pipette tip, such as pipette tip 214, to be inserted between inflatable sleeve 228 and stop 240.
[0054] FIG. 2E illustrates a cross-section view of sample channel pump 226 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2E shows sample channel pump 226 performing an aspiration process of a sample 242.
[0055] In some aspects, sample channel pump 226 can be coupled to sample channel 224. Sample channel pump 226 can be configured to create a pressure differential that moves a sample in a given direction through pipette tip 214. For example, the pressure differential can move sample 242 into pipette tip 214 in aspiration direction 244. In some aspects, sample channel pump 226 can include a pressure chamber 246, a piston 252, and a sealing apparatus 254.
[0056] In some aspects, pressure chamber 246 can be a hollow cavity disposed within pipette apparatus 203. Pressure chamber 246 can include a first end 248 coupled to the sample channel 224 and a second end 250. Pressure chamber 246 can be configured to hold piston 252 and a volume of air or the like. [0057] In some aspects, piston 252 can be disposed within pressure chamber 246. Piston 252 can be configured to create, through movement of piston 252 relative to pressure chamber 246 and the chamber walls created by pipette apparatus 203, the pressure differential that moves sample 242 in the given direction through pipette tip 214.
[0058] In some aspects, sealing apparatus 254 can be disposed at second end 250 of pressure chamber 246. Sealing apparatus 254 can secure piston 252 to pressure chamber 246. In some aspects, sealing apparatus 254 can be a mechanical seal such as, for example, an O-ring. A skilled artisan would recognize that sealing apparatus 254 can alternatively be placed on an end of piston 252 within pressure chamber 246 near first end 248.
[0059] In some aspects, in an example operation, robot arm 102 can move pipette apparatus 203 to insert pipette tip 214 into a sample 242. Once pipette tip 214 is inserted into sample 242, an actuator 105 can move piston 252 to draw up sample 242 into pipette tip 214. Specifically, as shown in FIG. 2E, piston 252 can move in aspiration direction 244 to increase a volume of air present in pressure chamber 246. As a result, in this example, a pressure of the air decreases and sample 242 can flow into pipette tip 214 in aspiration direction 244. In this configuration, robot arm 102 can transport pipette apparatus 203 around the biological processing environment while pipette tip 214 carries sample 242.
[0060] FIG. 2F illustrates a cross-section view of sample channel pump 226 of pipette apparatus 203, according to some aspects. Specifically, FIG. 2F shows sample channel pump 226 performing a dispensing process of a sample.
[0061] In some aspects, sample channel pump 226 can be configured to create a pressure differential that moves a sample in a given direction through the pipette tip 214. For example, the pressure differential can move sample 242 out from pipette tip 214 in dispensing direction 245.
[0062] In some aspects, in an example operation, robot arm 102 can move pipette apparatus 203 to a target area while pipette tip 214 carries sample 242. Once pipette apparatus 203 is positioned at the target area, an actuator 105 can move piston 252 to push out sample 242 from pipette tip 214. Specifically, as shown in FIG. 2F, piston 252 can move in dispensing direction 245 to decrease a volume of air present in pressure chamber 246. As a result, in this example, a pressure of the air increases and sample 242 can flow out from pipette tip 214 in dispensing direction 245. In this configuration, robot arm 102 can use pipette apparatus 203 to dispense sample 242 at a target area within the biological processing environment.
[0063] FIG. 2G illustrates a cross-section view of a pipette apparatus 204, according to some aspects. In some aspects, pipette apparatus 204 can be a multichannel pipette device having an array of pipette manifolds 222 configured to interact with corresponding ones of pipette tips 214 arranged in an array. In some aspects, pipette apparatus 204 as shown in FIG. 2G can be a cross-section of pipette apparatus 104 as shown in FIGS. 1 A and IB.
[0064] In some aspects, pipette apparatus 204 can include a plurality of pipette apparatuses 203 arranged in an array of any number of rows and columns. In some aspects, as shown in the example aspect of FIGS. 1 A and IB, the multichannel pipette device of pipette apparatus 104 can have 96 pipette manifolds arranged in an array that matches the array of pipette tips 114. For example, the 96 pipette manifolds can be arranged in an 8x12 array. In this example, because pipette apparatus 204 can be a cross-section of pipette apparatus 104, pipette apparatus 204 is depicted as a cross-section of a row of 8 pipette apparatuses 203. Accordingly, the discussion of components of pipette apparatus 203 described with reference to FIGS. 2A-2F applies to the discussion of components of pipette apparatus 204 and reference numerals are not repeated on FIG. 2G for clarity.
[0065] In some aspects, pipette apparatus 204 can include one or more pipette manifolds 222, one or more sample channels 224, one or more sample channel pumps 226, one or more inflatable sleeves 228, and one or more fluid channels 230 (depicted by reference to pipette apparatuses 203, shown in FIGS. 2A-F).
[0066] In some aspects, each of the one or more pipette manifolds 222 can be sized and shaped to receive a corresponding pipette tip 214.
[0067] In some aspects, each of the one or more sample channels 224 can be disposed within a corresponding one of the one or more pipette manifolds 222.
[0068] In some aspects, one or more sample channel pumps 226 can be coupled to the one or more sample channels 224. The one or more sample channel pumps 226 can be configured to create a pressure differential that moves a sample 242 in a given direction through the corresponding pipette tip 214. In some aspects, at least one of the one or more sample channel pumps 226 can include a pressure chamber 246, a piston 252, and a sealing apparatus 254. In some aspects, pressure chamber 246 can include a first end 248 coupled to a corresponding one of the one or more sample channels 224 and a second end 250. In some aspects, piston 252 can be disposed within pressure chamber 246. Piston 252 can be configured to create the pressure differential that moves sample 242 in the given direction through the corresponding pipette tip 214. In some aspects, sealing apparatus 254 can be disposed at second end 250 of pressure chamber 246. Sealing apparatus 254 can secure piston 252 to pressure chamber 246.
[0069] In some aspects, each of the one or more inflatable sleeves 228 can be disposed over a corresponding one of the one or more pipette manifolds 222. Each of the one or more inflatable sleeves 228 can be made from a flexible material. In some aspects, each of the one or more inflatable sleeves 228 can be individual components. In some aspects, each of the one or more inflatable sleeves 228 can be protrusions from a continuous overlay component that fits across all of pipette manifolds 222. In some aspects, each of the one or more inflatable sleeves 228 is sealed to a corresponding one of the one or more pipette manifolds 222 by at least one of an adhesive material 232 or a compression device 234.
[0070] In some aspects, each of the one or more inflatable sleeves 228 is configured to fill with fluid 218 supplied from the one or more fluid channels 230 to secure the corresponding one of the one or more pipette manifolds 222 to the corresponding pipette tip 214 when the corresponding one of the one or more pipette manifolds 222 is inserted into the corresponding pipette tip 214. Accordingly, each of the one or more inflatable sleeves 228 is configured to secure the corresponding one of the one or more pipette manifolds 222 to the corresponding pipette tip 214 via static friction.
[0071] In some aspects, each of one or more stops 240 can be located at a distance around corresponding ones of the one or more inflatable sleeves 228. Each stop 240 can be sized, shaped, and positioned to prevent the corresponding inflatable sleeve 228 from expanding beyond a given point when no pipette tip is present.
[0072] In some aspects, one or more fluid channels 230 can form at least a portion of a fluidic path between reservoir 106 and the one or more inflatable sleeves 228. For example, all of the one or more fluid channels 230 can be connected fluidically to be actuated by a sleeve pump 108. In the example aspect described with reference to FIGS. 1A and IB, all 96 fluid channels 230 may be connected fluidically. In some aspects, at least one of the one or more fluid channels 230 can be disposed within a corresponding one of the one or more pipette manifolds 222. In some aspects, at least one of the one or more fluid channels 230 can be disposed outside of a corresponding one of the one or more pipette manifolds 222. [0073] In some aspects, each of the sample channel pumps 226 can be coupled to a corresponding one of the one or more sample channels 224. In some aspects, each of the one or more fluid channels 230 forms at least a portion of a fluidic path between reservoir 106 and a corresponding one of the one or more inflatable sleeves 228. In some aspects, sleeve pump 108 can be configured to supply fluid 118 from reservoir 106 to each of the one or more inflatable sleeves 228 via a corresponding one of the one or more fluid channels 230.
[0074] Returning to FIG. 2B, in some aspects, in an example operation, robot arm 102 can move pipette apparatus 203 toward a disposal area to eject pipette tip 214 that has been contaminated. In some aspects, sensor 210 can detect at least one of a pressure or volume of fluid in inflatable sleeve 228. In some aspects, controller 212 can compare the detected value of a pressure or volume against a threshold value to determine whether pressure or volume is too high in inflatable sleeve 228 for the ejection process. In response to the comparison, controller 212 can send a signal to sleeve pump 108 to reduce an amount of fluid in inflatable sleeve 228, thereby establishing deflated state 236. As a result, the reduction in the amount of fluid of inflatable sleeve 228 can allow for release of the pipette tip 214 from pipette manifold 22. Pipette tip 214 may be ejected via gravity or an ejection apparatus.
[0075] FIG. 3 illustrates a cross-section view of an ejection apparatus 356 on pipette apparatus 304, according to some aspects. In some aspects, pipette apparatus 304 can be a multichannel pipette device having a plurality of pipette manifolds 322. In some aspects, pipette apparatus 304 as shown in FIG. 3 can be a cross-section of pipette apparatus 104 as shown in FIGS. 1A and IB. A skilled artisan would recognize that ejection apparatus 356 can also be used with a single-pipette device such as, for example, pipette apparatus 203 as shown in and described with reference to FIGS. 2A-2F.
[0076] In some aspects, ejection apparatus 356 can be mounted anywhere on pipette apparatus 304 that enables ejection of pipette tips 314. In some aspects, ejection apparatus 356 can be mounted on pipette apparatus 304 with fasteners such as bolts, adhesive, magnets, clips, rotatable cams, or the like. In the example aspect shown in FIG. 3, ejection apparatus 356 can be mounted inside pipette apparatus 304. While FIG. 3 shows a crosssection of ejection apparatus 356, a skilled artisan would understand that ejection apparatus 356 can be a single plate that surrounds multiple or all of pipette manifolds 322. Alternatively, each pipette manifold 322 may be fitted with its own independent ejection apparatus 356.
[0077] In some aspects, ejection apparatus 356 can be configured to eject pipette tips 314 disposed on corresponding ones of pipette manifolds 322. Ejection apparatus 356 can have an ejector surface 359. When pipette ejection is not desired (e.g., an ejector rest state), ejection apparatus 356 can be positioned at a location where ejector surface 359 would not contact pipette tips 314. When pipette tips 314 are to be ejected, actuators 105 can move ejection apparatus 356 in ejection direction 357. When ejector surface 359 makes contact with pipette tips 314 (the position illustrated in FIG. 3), actuators 105 can continue moving ejector surface 359 in ejection direction 357 until pipette tips 314 separate from the corresponding pipette manifolds 322. In some aspects, ejector surface 359 can be a substantially uniform surface that ejects most or all pipette tips 314 at once. In some aspects, as shown in the example aspect of FIG. 3, ejector surface 359 can have a stairstep surface to eject a few pipette tips 314 at a time as ejector surface 359 moves further in the ejection direction 357 to minimize ejection forces. For example, as illustrated in the example aspect of FIG. 3, ejector surface 359 can be higher in the middle of the apparatus than on the edges.
[0078] In some aspects, actuator 105 can move ejection apparatus 356 opposite to ejection direction 357 to return ejection apparatus 356 to its rest state. Additionally or alternatively, as illustrated in FIG. 3, ejection apparatus 356 can include a spring-loaded mechanism 358. Spring-loaded mechanism 358 can be secured in place relative to pipette apparatus 104 and configured to have a rest state that keeps ejector surface 359 away from pipette tips 314. In some aspects, when actuators 105 move ejection apparatus 356 in an ejection direction 357, spring-loaded mechanism 358 is compressed. When actuators 105 disengage, the spring- loaded mechanism 358 can return to its uncompressed state, causing ejection surface 359 to move in a direction opposite to direction 357 and reset back to the rest state.
[0079] In some aspects, the movement of ejection apparatus 356 is independent of the movement of pistons 252. In other aspects, the movement of ejection apparatus 356 is coupled to the movement of pistons 252. In such aspects, the distance in direction 357 traveled by ejection apparatus 356 in order to eject pipette tips 314 can be a further extension of a distance traveled when pistons 252 perform a dispensing action. [0080] In some aspects, in an example operation, robot arm 102 can use pipette apparatus 304 to dispense a sample at a target area within the biological processing environment. Once the pipette tips 314 are empty, the pipette tips 314 can be ready for disposal. Actuators 105 can move ejection surface 359 in the ejection direction 357 to eject pipette tips 314 from the corresponding ones of pipette manifolds 322. In this configuration, system 100 can use ejection apparatus 356 to dispose of pipette tips 314 that have been used and/or contaminated.
Example Pipetting Method
[0081] FIG. 4 illustrates a method 460 of using a pipette apparatus (e.g., pipette apparatus 203 as shown in and described with reference to FIGS. 2A-2F) in a biological processing system (e.g., system 100 as shown in and described with reference to FIGS. 1A and IB), according to some aspects.
[0082] In some aspects, at step 462, a pipette manifold (e.g., pipette manifold 222 as shown in and described with reference to FIGS. 2A-2F) can be inserted into a pipette tip (e.g., pipette manifold 214 as shown in and described with reference to FIGS. 2A-2F). The pipette manifold can have an inflatable sleeve (e.g., inflatable sleeve 228 as shown in and described with reference to FIGS. 2A-2F) disposed thereon.
[0083] In some aspects, at step 464, a fluid (e.g., fluid 118 as shown in and described with reference to FIGS. 1A and IB) stored in a reservoir (e.g., reservoir 106 as shown in and described with reference to FIGS. 1 A and IB) can be supplied, with a pump (e.g., sleeve pump 108 as shown in and described with reference to FIGS. 1 A and IB), to a fluid channel (e.g., fluid channel 230 as shown in and described with reference to FIGS. 2A-2F) disposed in fluid communication with the inflatable sleeve.
[0084] In some aspects, at step 466, the inflatable sleeve can be filled with an amount of fluid via the fluid channel.
[0085] In some aspects, at step 468, the pipette manifold can be secured to the pipette tip via static friction created by the filling.
[0086] In some aspects, method 460 can further include moving a piston (e.g., piston 252 as shown in and described with reference to FIGS. 2E-2F) in a first direction (e.g., aspiration direction 244 as shown in and described with reference to FIG. 2E) to aspirate a sample (e.g., sample 242 as shown in and described with reference to FIGS. 2E-2F) into the pipette tip, the piston disposed within a pressure chamber (e.g., pressure chamber 246 as shown in and described with reference to FIGS. 2E-2F) coupled to the sample channel.
[0087] In some aspects, method 460 can further include moving the piston in a second direction (e.g., dispensing direction 245 as shown in and described with reference to FIG. 2F) to dispense the sample from the pipette tip.
[0088] In some aspects, method 460 can further include deflating the inflatable sleeve by removing fluid from the inflatable sleeve via the fluid channel. The fluid may be removed by reversing a pumping direction of the pump (e.g., when the pump is a two-way pump) or by releasing a valve to change the pressure acting on the fluid (e.g., when the pump is a one-way pump).
[0089] In some aspects, method 460 can further include ejecting the pipette tip from the pipette manifold by activating a spring-loaded mechanism of an ejection apparatus (e.g., ejection apparatus 356 as shown in and described with reference to FIG. 3) coupled to the pipette manifold.
[0090] In some aspects, the pipette manifold can be a plurality of pipette manifolds, each pipette manifold having a corresponding inflatable sleeve. In some aspects, the fluid channel can be a plurality of fluid channels each disposed in fluid communication with a corresponding inflatable sleeve. In some aspects, the inserting comprises inserting each pipette manifold in the plurality of pipette manifolds into a corresponding pipette tip in a plurality of pipette tips. In some aspects, the supplying comprises supplying, with the pump, the fluid stored in the reservoir to the plurality of fluid channels. In some aspects, the filling comprises filling each inflatable sleeve with the amount of fluid via the corresponding fluid channel in the plurality of fluid channels. In some aspects, the securing comprises securing the each pipette manifold in the plurality of pipette manifolds to the corresponding pipette tip in the plurality of pipette tips via the static friction created by the filling.
[0091] In some aspects, method 460 can further include moving a robot arm (e.g., robot arm 102 as shown in and described with reference to FIGS. 1A and IB) coupled to the plurality of pipette manifolds to apply a substantially equal distribution of a Z-axis force (e.g., force 116 as shown in and described with reference to FIGS. 1 A and IB) across each pipette tip, the Z-axis force parallel to a length of each pipette tip and having a magnitude of less than approximately 50 N. [0092] In some aspects, method 460 can further include detecting, with a sensor (e.g., sensor 110 as shown in and described with reference to FIGS. 1 A and IB) coupled to each of all or a subset of the inflatable sleeves, at least one of a pressure or volume of the amount of the fluid in each of the inflatable sleeves. In some aspects, method 460 can further include adjusting, with the pump, the amount of the fluid in each of the inflatable sleeves based on the detecting.
[0093] The method steps of FIG. 4 can be performed in any reasonable order and it is not required that all steps be performed. Moreover, the method steps of FIG. 4 described above merely reflect an example of steps and are not limiting. That is, further method steps and functions are envisaged based on aspects described in reference to FIGS. 1A-3.
[0094] It is to be appreciated that the Detailed Description section, and not the Summary and Abstract sections, is intended to be used to interpret the claims. The Summary and Abstract sections may set forth one or more but not all exemplary aspects of the present invention as contemplated by the inventor(s), and thus, are not intended to limit the present invention and the appended claims in any way.
[0095] The aspects have been described above with the aid of functional building blocks illustrating the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternate boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed.
[0096] The foregoing description of the specific aspects will so fully reveal the general nature of the invention that others can, by applying knowledge within the skill of the art, readily modify and/or adapt for various applications such specific aspects, without undue experimentation, without departing from the general concept of the present invention. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed aspects, based on the teaching and guidance presented herein. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, such that the terminology or phraseology of the present specification is to be interpreted by the skilled artisan in light of the teachings and guidance.
[0097] The breadth and scope of the present invention should not be limited by any of the above-described exemplary aspects, but should be defined only in accordance with the following claims and their equivalents.

Claims

WHAT IS CLAIMED IS:
1. A system comprising: a reservoir configured to store a fluid; a robot arm; a pipette apparatus coupled to the robot arm, the pipette apparatus comprising: one or more pipette manifolds each sized and shaped to receive a corresponding pipette tip; one or more sample channels each disposed within a corresponding one of the one or more pipette manifolds; one or more sample channel pumps coupled to the one or more sample channels and configured to create a pressure differential that moves a sample in a given direction through the corresponding pipette tip; one or more inflatable sleeves each comprising a flexible material and disposed over a corresponding one of the one or more pipette manifolds; and one or more fluid channels forming at least a portion of a fluidic path between the reservoir and the one or more inflatable sleeves; and a sleeve pump coupled to the reservoir and the one or more fluid channels, the sleeve pump configured to supply the fluid from the reservoir to the one or more inflatable sleeves via the one or more fluid channels.
2. The system of claim 1, wherein each of the one or more inflatable sleeves is configured to fill with fluid supplied from the one or more fluid channels to secure the corresponding one of the one or more pipette manifolds to the corresponding pipette tip when the corresponding one of the one or more pipette manifolds is inserted into the corresponding pipette tip.
3. The system of claim 2, wherein each of the one or more inflatable sleeves is configured to secure the corresponding one of the one or more pipette manifolds to the corresponding pipette tip via static friction.
4. The system of claim 1, wherein: each of the sample channel pumps is coupled to a corresponding one of the one or more sample channels; each of the one or more fluid channels forms at least a portion of a fluidic path between the reservoir and a corresponding one of the one or more inflatable sleeves; and the sleeve pump is configured to supply the fluid from the reservoir to each of the one or more inflatable sleeves via a corresponding one of the one or more fluid channels.
5. The system of claim 1, wherein at least one of the one or more fluid channels is disposed within a corresponding one of the one or more pipette manifolds.
6. The system of claim 1, wherein at least one of the one or more fluid channels is disposed outside of a corresponding one of the one or more pipette manifolds.
7. The system of claim 1, wherein the flexible material comprises at least one of an elastic material, a rubber material, or a latex material.
8. The system of claim 1, wherein each of the one or more inflatable sleeves is sealed to a corresponding one of the one or more pipette manifolds by at least one of an adhesive material or a compression device.
9. The system of claim 1, wherein at least one of the one or more sample channel pumps comprises: a pressure chamber comprising a first end coupled to a corresponding one of the one or more sample channels and a second end; a piston disposed within the pressure chamber, the piston configured to create the pressure differential that moves the sample in the given direction through the corresponding pipette tip; and a sealing apparatus disposed at the second end of the pressure chamber and securing the piston to the pressure chamber.
10. The system of claim 1, wherein the pipette apparatus further comprises an ejection apparatus comprising a spring-loaded mechanism configured to eject each pipette tip disposed on corresponding ones of the one or more pipette manifolds.
11. The system of claim 1, wherein the sleeve pump comprises a two-way sleeve pump configured to supply and withdraw the fluid at each of the one or more fluid channels.
12. The system of claim 1, wherein the sleeve pump comprises a one-way sleeve pump configured to supply the fluid to each of the one or more fluid channels.
13. The system of claim 1, wherein the robot arm is configured to apply a substantially equal distribution of a Z-axis force across each pipette tip, the Z-axis force parallel to a length of each pipette tip and comprising a magnitude of less than approximately 50 N.
14. The system of claim 1, further comprising: a sensor coupled to each of the one or more inflatable sleeves, the sensor configured to detect at least one of a pressure or volume of fluid in each of the one or more inflatable sleeves; and a controller coupled to the sensor and the sleeve pump, the controller configured to send a signal to the sleeve pump to adjust an amount of the fluid in each of the one or more inflatable sleeves based on at least one of the pressure or volume of the fluid detected by the sensor.
15. The system of claim 1, further comprising: one or more stops each located at a distance around corresponding ones of the one or more inflatable sleeves, each stop sized, shaped, and positioned to prevent the corresponding inflatable sleeve from expanding beyond a given point when no pipette tip is present.
16. A pipette apparatus comprising: a pipette manifold sized and shaped to receive a pipette tip; a sample channel disposed within the pipette manifold; a sample channel pump coupled to the sample channel and configured to create a pressure differential that moves a sample in a given direction through the pipette tip; an inflatable sleeve comprising a flexible material and disposed over the pipette manifold; and a fluid channel forming at least a portion of a fluidic path between a reservoir and the inflatable sleeve.
17. The pipette apparatus of claim 16, wherein the inflatable sleeve is configured to fill with fluid supplied from the fluid channel to secure the pipette manifold to the pipette tip when the pipette manifold is inserted into the pipette tip.
18. The pipette apparatus of claim 17, wherein the inflatable sleeve is configured to secure the pipette manifold to the pipette tip via static friction.
19. The pipette apparatus of claim 16, wherein the fluid channel is disposed within the pipette manifold.
20. The pipette apparatus of claim 16, wherein the fluid channel is disposed outside of the pipette manifold.
21. The pipette apparatus of claim 16, wherein the flexible material comprises at least one of an elastic material, a rubber material, or a latex material.
22. The pipette apparatus of claim 16, wherein the inflatable sleeve is sealed to the pipette manifold by at least one of an adhesive material or a compression device.
23. The pipette apparatus of claim 16, wherein the sample channel pump comprises: a pressure chamber comprising a first end coupled to the sample channel and a second end; a piston disposed within the pressure chamber, the piston configured to create the pressure differential that moves the sample in the given direction through the pipette tip; and a sealing apparatus disposed at the second end of the pressure chamber and securing the piston to the pressure chamber.
24. The pipette apparatus of claim 16, further comprising an ejection apparatus comprising a spring-loaded mechanism configured to eject the pipette tip disposed on the pipette manifold.
25. The pipette apparatus of claim 16, further comprising: a sensor coupled to the inflatable sleeve, the sensor configured to detect at least one of a pressure or volume of fluid in the inflatable sleeve; and a controller coupled to the sensor and a sleeve pump, the controller configured to send a signal to the sleeve pump to adjust an amount of the fluid in the inflatable sleeve based on at least one of the pressure or volume of the fluid detected by the sensor.
26. The pipette apparatus of claim 16, further comprising: a stop located at a distance around the inflatable sleeve, the stop sized, shaped, and positioned to prevent the inflatable sleeve from expanding beyond a given point when no pipette tip is present.
27. A method comprising: inserting a pipette manifold having an inflatable sleeve disposed thereon into a pipette tip; supplying, with a pump, a fluid stored in a reservoir to a fluid channel disposed in fluid communication with the inflatable sleeve; filling the inflatable sleeve with an amount of fluid via the fluid channel; and securing the pipette manifold to the pipette tip via static friction created by the filling.
28. The method of claim 27, further comprising moving a piston in a first direction to aspirate a sample into the pipette tip, the piston disposed within a pressure chamber coupled to the sample channel.
29. The method of claim 28, further comprising moving the piston in a second direction to dispense the sample from the pipette tip.
30. The method of claim 27, further comprising ejecting the pipette tip from the pipette manifold by activating a spring-loaded mechanism of an ejection apparatus coupled to the pipette manifold.
31. The method of claim 27, wherein: the pipette manifold is a plurality of pipette manifolds, each pipette manifold having a corresponding inflatable sleeve; the fluid channel is a plurality of fluid channels each disposed in fluid communication with a corresponding inflatable sleeve; the inserting comprises inserting each pipette manifold in the plurality of pipette manifolds into a corresponding pipette tip in a plurality of pipette tips; the supplying comprises supplying, with the pump, the fluid stored in the reservoir to the plurality of fluid channels; the filling comprises filling each inflatable sleeve with the amount of fluid via the corresponding fluid channel in the plurality of fluid channels; and the securing comprises securing the each pipette manifold in the plurality of pipette manifolds to the corresponding pipette tip in the plurality of pipette tips via the static friction created by the filling.
32. The method of claim 31, further comprising moving a robot arm coupled to the plurality of pipette manifolds to apply a substantially equal distribution of a Z-axis force across each pipette tip, the Z-axis force parallel to a length of each pipette tip and comprising a magnitude of less than approximately 50 N.
33. The method of claim 31, further comprising: detecting, with a sensor coupled to each of the inflatable sleeves, at least one of a pressure or volume of the amount of the fluid in the each of the inflatable sleeves; and adjusting, with the pump, the amount of the fluid in the each of the inflatable sleeves based on the detecting.
PCT/US2025/014871 2024-02-06 2025-02-06 Inflatable sleeve pipette system and apparatus Pending WO2025171185A1 (en)

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US63/550,197 2024-02-06

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06323964A (en) * 1993-05-13 1994-11-25 Japan Energy Corp Liquid sample dispenser
US5734114A (en) * 1995-08-31 1998-03-31 Itoh; Teruaki Nozzle apparatus for sampling and dispensing specimen
US6673318B1 (en) * 1999-05-31 2004-01-06 Bridgestone Corporation Pipette
US20190255533A1 (en) * 2016-06-29 2019-08-22 Eppendorf Ag Metering Head, Metering Device Comprising a Metering Head, and Method for Metering by Means of a Metering Head
CN211936974U (en) * 2020-04-09 2020-11-17 蒋晶 Hydrogeology chemistry inspection is with moving liquid device

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06323964A (en) * 1993-05-13 1994-11-25 Japan Energy Corp Liquid sample dispenser
US5734114A (en) * 1995-08-31 1998-03-31 Itoh; Teruaki Nozzle apparatus for sampling and dispensing specimen
US6673318B1 (en) * 1999-05-31 2004-01-06 Bridgestone Corporation Pipette
US20190255533A1 (en) * 2016-06-29 2019-08-22 Eppendorf Ag Metering Head, Metering Device Comprising a Metering Head, and Method for Metering by Means of a Metering Head
CN211936974U (en) * 2020-04-09 2020-11-17 蒋晶 Hydrogeology chemistry inspection is with moving liquid device

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