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WO2025171185A1 - Système et appareil à pipette à manchon gonflable - Google Patents

Système et appareil à pipette à manchon gonflable

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
English (en)
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/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/103—General 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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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

Un système donné à titre d'exemple comprend un réservoir de fluide, un bras robotique, un appareil à pipette et une pompe de manchon. L'appareil à pipette est couplé au bras robotique et comprend un collecteur de pipette, un canal d'échantillon, une pompe de canal d'échantillon, un manchon gonflable et un canal de fluide. La pompe de canal d'échantillon est couplée au canal d'échantillon et crée un différentiel de pression qui déplace un échantillon dans une direction donnée, à travers une pointe de pipette disposée sur le collecteur de pipette. Le manchon gonflable est disposé sur le collecteur de pipette. La pompe de manchon fournit le fluide du réservoir au manchon gonflable par l'intermédiaire du canal de fluide. Lorsqu'il est gonflé, le manchon gonflable fixe une pointe de pipette sur le collecteur de pipette.
PCT/US2025/014871 2024-02-06 2025-02-06 Système et appareil à pipette à manchon gonflable Pending WO2025171185A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202463550197P 2024-02-06 2024-02-06
US63/550,197 2024-02-06

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WO2025171185A1 true WO2025171185A1 (fr) 2025-08-14

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06323964A (ja) * 1993-05-13 1994-11-25 Japan Energy Corp 液体試料の分注装置
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 (zh) * 2020-04-09 2020-11-17 蒋晶 一种水文地质化学检验用移液装置

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06323964A (ja) * 1993-05-13 1994-11-25 Japan Energy Corp 液体試料の分注装置
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 (zh) * 2020-04-09 2020-11-17 蒋晶 一种水文地质化学检验用移液装置

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