SE543488C2 - A liquid media handling system and a connecting receptable adapted for use in said system - Google Patents

A liquid media handling system and a connecting receptable adapted for use in said system

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Publication number
SE543488C2
SE543488C2 SE1850835A SE1850835A SE543488C2 SE 543488 C2 SE543488 C2 SE 543488C2 SE 1850835 A SE1850835 A SE 1850835A SE 1850835 A SE1850835 A SE 1850835A SE 543488 C2 SE543488 C2 SE 543488C2
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SE
Sweden
Prior art keywords
connecting receptacle
receiving element
receptacle
ofthe
liquid
Prior art date
Application number
SE1850835A
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Swedish (sv)
Other versions
SE1850835A1 (en
Inventor
Håkan Jönsson
Krzysztof Langer
Original Assignee
Joensson Haakan
Krzysztof Langer
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Publication date
Application filed by Joensson Haakan, Krzysztof Langer filed Critical Joensson Haakan
Priority to SE1850835A priority Critical patent/SE543488C2/en
Publication of SE1850835A1 publication Critical patent/SE1850835A1/en
Publication of SE543488C2 publication Critical patent/SE543488C2/en

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    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0289—Apparatus for withdrawing or distributing predetermined quantities of fluid
    • B01L3/0293—Apparatus for withdrawing or distributing predetermined quantities of fluid for liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/56—Labware specially adapted for transferring fluids
    • B01L3/565—Seals
    • 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
    • G01N35/0099—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Robotics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)

Abstract

A liquid media handling system (1) for dispensing and collecting liquids to or from a receiving element (3), comprising an elongated connecting receptacle (2) witha lower end (4) formed to fit into a round receiving element (3) having an internal diameter of 0.05 to 10 mm and an upper end (5) adapted for reversibly sealing with a movable actuating device (6) such that the connecting receptacle (2) can be disconnected from the movable actuating device (6) with a force A in direction X (7); characterized in that the connecting receptacle (2) comprises an elastic sleeve (9) arranged around the lower end (4) of the connecting receptacle (2); the connecting receptacle (2) lower end (4) and the elastic sleeve (9) are configured to form a reversible seal with the receiving element (3) when the connecting receptacle (2) is inserted into the receiving element (3), such that the connecting receptacle (2) can be unsealed from the receiving element (3) with a force B in direction Y (8); and wherein force B is smaller than force A, and directions X and Y are opposite, and wherein the connecting receptacle (2) further comprises a spring (12) located around and outside of said connecting receptacle (2), configured such that when the connecting receptacle (2) and the receiving element (3) have formed a seal, the spring (12) is in a compressed state pushing the connecting receptacle and the receiving element (3) apart. A connecting receptacle for the system is also disclosed.

Description

A LIQUID MEDIA HANDLING SYSTEM AND A CONNECTING RECEPTACLE ADAPTED FOR USEIN SAID SYSTEM TECHNICAL FIELDThe present invention relates to field of liquid media handling systems for dispensing and collecting liquids to or from a receiving element, such as a microfluidic chip.
BACKGROUND TO THE INVENTION Laboratory automation is becoming ever more common and essential in the life sciences, asit has the potential to increase the quantity and quality of experiments that can becompleted in parallel with reduced manual labor (Khalid et al. DO|:10.1101/209957).Laboratory automation opens new possibilities for science, such as cloud labs, where fullyautomated computer-controlled scientific protocols are performed remotely by robots,allowing for scientific experiments to be outsourced and performed at a distance from the scientist. ln this context, liquid handling, and more importantly fully automated liquid handlingperformed by laboratory robots is an essential part of innovation in science in general, andmore precisely in laboratory workflows. For many experiments in the life sciences, liquidhandling is a key component and an essential core element of laboratory automation. lnmodern life science laboratories, high-throughput liquid handling is frequently needed for improved efficiency (Kong et al. DOI:10.1177/2211068211435302).
I\/licrofluidics is a technology characterized by the engineered manipulation of fluids at thesub-millimeter scale with miniaturized devices designed to perform multi-step laboratorytasks that normally require well-equipped full-size laboratory. Such devices have shownconsiderable promise for improving diagnostics and biology research. Rapid sampleprocessing and the precise control of fluids are the key properties of microfluidictechnologies, making both simple and complex microfluidic chips attractive candidates to replace traditional experimental approaches (Sackmann et al. DOI:10.1038/nature13118).
However, automating microfluidics or combining microfluidics with existing automatedprotocols with a liquid handling robots playing a pivotal role, although an apparent logical next step, is not trivial and requires additional advances in technology. lt is an object ofthe present invention to provide an improved liquid media handling systemand component parts for automated liquid media handling for dispensing and collectingliquids. The present invention aims to allow for an easy and fail-free interaction between aliquid handling robot, a microfluidic chip and other standardized already widely used in lifescience equipment such as pipetting tips, multi-well plates, plastic tubes etc., repeatedly and with a minimal need for human supervision.
BRIEF DESCRIPTION OF THE FIGURES For ease of reference, the components shown in the figures are summarized in the following table: Component Designation 1 Liquid media handling system 2 Connecting receptacle 3 Receiving element 4 Lower end of connecting receptacle (2) Upper end of connecting receptacle (2) 6 I\/|ovable actuating device 7 Force A in direction X (illustrated by an arrow)8 Force B in direction Y (illustrated by an arrow)9 Elastic sleeve Source of negative or positive pressure 11 Guide element 12 Spnng 13 Means for preventing flow of liquid 14 Magnetic valve element Magnetic element outside of connecting receptacle (2)16 Tapering tubular segment 17 Vent for regulation of pressure 18 External reservoir Figure 1. A liquid handling system with a sealed interface between the movable liquid mediadispenser and at least one well when in contact: 1 - Liquid handling system, 2 - Connectingreceptacle, 3 - Receiving element, 4 - Lower end of connecting receptacle (2), 5 - Upper endof connecting receptacle (2), 6 - I\/|ovable actuating device, 7 - Force A in direction X (illustrated by an arrow), 8 - Force B in direction Y (illustrated by an arrow), 9 - Elastic sleeve.
Figure 2. A controllable liquid handling system that prevents passively or actively the liquidstored in the system to flow without a control: 1 - Liquid handling system, 2 - Connectingreceptacle,3 - Receiving element, 4 - Lower end of connecting receptacle (2), 5 - Upper endof connecting receptacle (2), 6 - I\/|ovable actuating device, 7 - Force A in direction X(illustrated by an arrow), 8 - Force B in direction Y (illustrated by an arrow), 9 - Elastic sleeve,10 - Source of negative or positive pressure, 13 - Means for preventing flow of liquid, 14 - I\/|agnetic valve element, 15 - I\/|agnetic element outside of connecting receptacle (2).
Figure 3. A liquid handling system that can interface with multiple wells made of differentmaterials, maintaining similar sealed connection during each interaction and providing asimilar easy detachment from each well: 1 - Liquid handling system, 2 - Connectingreceptacle, 3 - Receiving element, 4 - Lower end of connecting receptacle (2), 5 -Upper endof connecting receptacle (2), 6 - I\/|ovable actuating device, 7 - Force A in direction X(illustrated by an arrow), 8 - Force B in direction Y (illustrated by an arrow), 9 - Elasticsleeve, 12 - Spring, 13 - Means for preventing flow of liquid, 14 - I\/|agnetic valve element, 15 - I\/|agnetic element outside of connecting receptacle (2), 17 - Vent for regulation of pFeSSUFe Figure 4. A liquid handling system that comprises a guiding element to help align theconnecting receptacle (2) and the receiving element (3) and an external reservoir (18) forcollecting or dispensing liquids with a valving element integrated to prevent a free flow ofstored liquids when the connecting receptacle (2) is not sealed to receiving element (3): 1 -Liquid handling system, 2 - Connecting receptacle, 3 - Receiving element, 4 - Lower end ofconnecting receptacle (2), 5 - Upper end of connecting receptacle (2), 6 - I\/|ovable actuatingdevice, 7 - Force A in direction X (illustrated by an arrow), 8 - Force B in direction Y(illustrated by an arrow), 9 - Elastic sleeve, 10 - Source of negative or positive pressure, 11 -Guide element, 12 - Spring, 13 - Means for preventing flow of liquid, 14 - I\/|agnetic valveelement, 15 - I\/|agnetic element outside of connecting receptacle (2), 17 - Vent for regulation of pressure, 16 - Tapering tubular segment, 18 - External reservoir SUMMARY OF THE INVENTIONThe present invention relates to the following items. The subject matter disclosed in theitems below should be regarded disclosed in the same manner as ifthe subject matter were disclosed in patent claims. 1. A liquid media handling system (1) for dispensing and collecting liquids to or from a receiving element (3), comprising: an elongated connecting receptacle (2) with a lower end (4) formed to fit into a round receiving element (3) having aninternal diameter of 0.05 to 10 mm and an upper end (5) adapted for reversibly sealing with a movable actuatingdevice (6) such that the connecting receptacle (2) can be disconnected from the movable actuating device (6) with a force A in direction X (7);characterized in that the connecting receptacle (2) comprises an elastic sleeve (9) arranged around the lower end (4) ofthe connecting receptacle (2), the connecting receptacle (2) lower end (4) and the elastic sleeve (9) are configured to form a reversible seal with the receiving element (3) when the connecting receptacle (2) is inserted into the receiving element (3), such thatthe connecting receptacle (2) can be unsealed from the receiving element (3) with a force B in direction Y (8); and wherein force B is smaller than force A, and directions X and Y are opposite,and wherein the connecting receptacle (2) further comprises a spring (12)located around and outside of said connecting receptacle (2), configured suchthat when the connecting receptacle (2) and the receiving element (3) haveformed a seal, the spring (12) is in a compressed state pushing the connecting receptacle and the receiving element (3) apart.
The liquid media handling system (1) according to claim 1, wherein the movableactuating device (6) comprises a source (10) of negative or positive pressureconfigured to communicate with the inside ofthe connecting receptacle (2), whenthe upper end (5) ofthe connecting receptacle (2) is sealed with the movable actuating device (6).
The liquid media handling system (1) according to any ofthe preceding claims, wherein the lower end (4) ofthe connecting receptacle (2) has a conical shape.
The liquid media handling system (1) according to any ofthe preceding claims,wherein the system further comprises a guide element (11) configured to align theconnecting receptacle (2) and the receiving element (3) to facilitate inserting the connecting receptacle (2) into the receiving element (3).
The liquid media handling system (1) according to any ofthe preceding claims,wherein the system further comprises a means (13) for preventing flow of liquidwhen the connecting receptacle (2) is not sealed to receiving element (3), said means being integrated in the connecting receptacle (2).
The liquid media handling system (1) according to claim 5, wherein the means (13)for preventing flow of liquid comprises a valve with a movable magnetic valveelement (14) capable of blocking the passage of fluid through the connecting receptacle (2), located inside the connecting receptacle (2); and . 11. 12. 13. 14. the system comprises a magnetic element (15) outside ofthe connecting receptacle(2) capable of shifting the magnetic valve element (14) between a position blockingthe passage of fluid through the connecting receptacle (2) and a position not blocking said passage.
The liquid media handling system (1) according to claim 6, wherein the connectingreceptacle (2) comprises a tapering tubular segment (16) housing the magnetic valveelement (14), said tubular segment (16) and valve element (14) being shaped anddimensioned such that the valve element (14) can be positioned to either block or allow liquid flow through the tubular segment (16).
The liquid media handling system (1) according to claim 7, wherein the tubular segment (16) is conical.
The liquid media handling system (1) according to claim 7 or 8, wherein the valve element (14) is spherical.
The liquid media handling system (1) according to any ofthe preceding claims,wherein the elastic sleeve (9) comprises any of the following materials:tetrafluoroethylene (TFE) and its polymers, commonly called Teflon and Fluon, synthetic rubber (elastomers), cork, leather, metal or asbestos.
The liquid media handling system (1) according to any ofthe preceding claims,comprising means for applying positive pressure to the inside of the connecting receptacle (2), to dispense liquid.
The liquid media handling system (1) according to any ofthe preceding claims,comprising means for applying negative pressure to the inside of the connecting receptacle (2), to collect liquid.
The liquid media handling system (1) according to any ofthe preceding claims,wherein the connecting receptacle (2) comprises a vent (17) for regulation ofthe internal pressure.
The liquid media handling system (1) according to any ofthe preceding claims,wherein the connecting receptacle (2) is configured to seal with a female micro-Luer or Luer fitting located on the receiving element (3). . 16. 17. 18. 19. . 21.
The liquid media handling system (1) according to any ofthe preceding claims, comprising an external reservoir (18) for liquids to be dispensed or collected.
The liquid media handling system (1) according to any ofthe preceding claims,wherein the connecting receptacle (2) comprises a pipette tip, preferably a standard 1 ml pipette tip.
The liquid media handling system (1) according to any ofthe preceding claims, wherein the connecting receptacle (2) is detachable from the rest ofthe system.
The liquid media handling system (1) according to any ofthe preceding claims, wherein the movable actuating device (6) is a pipetting robot.
The liquid media handling system (1) according to any ofthe preceding claims,wherein the system is adapted to liquid handling on a scale of 0.1-1000 ml, preferably 0.01-100 ml, more preferably 0.01-10 ml.
A method for dispensing and collecting liquids using a liquid media handling system (1) according to any of claims 1 - 19.The method according to claim 20, comprising: a. Reversibly sealing the connecting receptacle (2) with the movable actuating device (6); b. lnserting the connecting receptacle (2) into the receiving element (3) thusforming a reversible seal between the connecting receptacle (2) and the receiving element (3), by way of operating the movable actuating device (6); c. Applying negative pressure to the inside ofthe connecting receptacle (2),thus collecting liquid from the receiving element (3) or alternatively, applyingpositive pressure to the inside ofthe connecting receptacle (2), thus dispensing liquid to the receiving element (3); and d. Pulling the connecting receptacle (2) out of the receiving element (3) thusreversing the seal between the receptacle and the receiving element (3), by way of moving the actuating device. 22. The method according to claim 21, further comprising disconnecting the connecting receptacle (2) from the movable actuating device (6) 23. A connecting receptacle (2) adapted for use in a liquid media handling system (1) according to any of claims 1 - 19, comprising: a lower end (4) formed to fit into a round receiving element (3) having an internaldiameter of 0.05 to 10 mm and an upper end (5) adapted for reversibly sealing with a movable actuating device (6)of said system such that the connecting receptacle (2) can be disconnected from themovable actuating device (6); characterized in that the connecting receptacle (2) comprises an elastic sleeve (9) arranged around thelower end (4) of the connecting receptacle (2); and the connecting receptacle (2) lower end (4) and the elastic sleeve (9) are configuredto form a reversible seal with the receiving element (3) when the connectingreceptacle (2) is inserted into the receiving element (3), such that the connecting receptacle (2) can be disconnected from the receiving element (3) and wherein the connecting receptacle (2) further comprises a spring (12) located aroundand outside said connecting receptacle (2), configured such that when theconnecting receptacle (2) and the receiving element (3) are in contact, the spring(12) is in a compressed state pushing the connecting receptacle and the receiving element (3) apart. 24. The connecting receptacle (2) according to claim 23, wherein the connectingreceptacle (2) is configured such that the connecting receptacle (2) can be disconnectedfrom the movable actuating device (6) with a force A in direction X (7), and such that theconnecting receptacle (2) can be disconnected from the receiving element (3) with aforce B in direction Y (8), wherein force B is smaller than force A and directions X and Y are opposite.
. The connecting receptacle (2) according to any of claims 23-24, wherein the elastic sleeve (9) comprises any of the following materials: tetrafluoroethylene (TFE) and its polymers, commonly called Teflon and Fluon, synthetic rubber (elastomers), cork, leather, metal or asbestos. 26. The connecting receptacle (2) according to any of claims 23-25, wherein the connecting receptacle (2) comprises a vent (17) for regulation ofthe internal pressure. 27. The connecting receptacle (2) according to any of claims 23-26, wherein the connectingreceptacle (2) further comprises a means (13) for preventing flow of liquid when the connecting receptacle (2) is not sealed to a receiving element (3). 28. The connecting receptacle (2) according to any of claims 23-27, wherein the means (13)for preventing flow of liquid comprises a valve with a movable magnetic valve element (14)capable of blocking the passage of fluid through the connecting receptacle (2), located inside the connecting receptacle (2). 29. The connecting receptacle (2) according to any of claims 23-28, wherein the connectingreceptacle (2) comprises a tapering tubular segment (16) housing the magnetic valveelement (14), said tubular segment (16) and valve element (14) being shaped anddimensioned such that the valve element (14) can be positioned to either block or allow liquid flow through the tubular segment (16).
. The connecting receptacle (2) according to claim 29, wherein the tubular segment (16) is conical. 31. The connecting receptacle (2) according to claim 29 or 30, wherein the valve element (14) is spherical. 32. The connecting receptacle (2) according to any of claims 23-31, wherein the lower end (4) ofthe connecting receptacle (2) has conical shape. connecting receptacle33. The connecting receptacle (2) according to any of claims 25-32, wherein the connecting receptacle (2) is configured to seal with a female micro-Luer or Luer fitting located on the receiving element (3).
DEFINITIONS ln the present context, the terms Luer and micro-Luer have their normal meanings in thefield. These fittings are well known in the field and strictly standardized. Reference is made to ISO 80369-7:2016(en), ISO 594-1 and ISO 594-2.
The general shape of a Luer fitting is that the male fitting has smooth surface and is conicalat 6% slope. The female connector is a smooth, tapering tubular element into which themale fitting snugly fits. To give a sense of scale, the inner diameter (ID) of a female Luer fitting is about 4 mm, and that of a micro-Luer is about 2.7 mm.
DETAILED DESCRIPTION Liquid media handling system ln a first aspect, the present invention provides a liquid media handling system (1) for dispensing and collecting liquids to or from a receiving element (3), comprising: an elongated connecting receptacle (2) with a lower end (4) formed to fit into a round receiving element (3) having an internal diameter of 0.05 to 10 mm and an upper end (5) adapted for reversibly sealing with a movable actuating device (6) suchthat the connecting receptacle (2) can be disconnected from the movable actuating device (6) with a force A in direction X (7);characterized in that the connecting receptacle (2) comprises an elastic sleeve (9) arranged around the lower end (4) ofthe connecting receptacle (2), the connecting receptacle (2) lower end (4) and the elastic sleeve (9) are configured to forma reversible seal with the receiving element (3) when the connecting receptacle (2) isinserted into the receiving element (3), such that the connecting receptacle (2) can be unsealed from the receiving element (3) with a force B in direction Y (8),wherein force B is smaller than force A, and directions X and Y are opposite.
The system may comprise an external reservoir (18) for liquids to be dispensed or collected. 11 The system may be adapted to liquid handling on a scale of 0.1-1000 ml, preferably 0.01-10O ml, more preferably 0.01-10 ml.
The connecting receptacle (2) is preferably detachable from the rest ofthe system, allowing the use of disposable components.
The connecting receptacle (2) may be in accordance with the third aspect ofthe present invention disclosed below.
The receiving element (3) may be a part of a more complex fluidic device (for example a milli-fluidic or microfluidic chip).Guide element The system may further comprise a guide element (11) configured to align the connectingreceptacle (2) and the receiving element (3) to facilitate inserting the connecting receptacle(2) into the receiving element (3). The guide element (11) may be implemented by way of a block comprising holes tapering towards the receiving element (3).
The connecting receptacle (2) may comprise a spring (12) located around and outside of saidconnecting receptacle (2), configured such that when the connecting receptacle (2) and thereceiving element (3) have formed a seal, the spring (12) is in a compressed state pushingthe connecting receptacle and the receiving element (3) apart. The spring (12) facilitatesdetaching the connecting receptacle (2) from the receiving element (3) but may alsofunction as a guide to facilitate inserting the connecting receptacle (2) to the receiving element (3).Means for preventing liquid flow The system may further comprise a means (13) for preventing flow of liquid when theconnecting receptacle (2) is not sealed to receiving element (3), said means being integratedin the connecting receptacle (2). The means may be as described in detail under the thirdaspect (see below). ln such case the system may further comprise a magnetic element (15)outside ofthe connecting receptacle (2) capable of shifting the magnetic valve element (14)between a position blocking the passage of fluid through the connecting receptacle (2) and a position not blocking said passage. 12 Movable actuating device The movable actuating device (6) may comprise a source (10) of negative or positivepressure configured to communicate with the inside of the connecting receptacle (2) whenthe upper end (5) ofthe connecting receptacle (2) is sealed with the movable actuating device (6).
A means for applying positive pressure to the inside ofthe connecting receptacle (2) allowsfor dispensing of liquid. A means for applying negative pressure to the inside of theconnecting receptacle (2) allows for collecting liquid. Preferably, the pressure source (10) can provide both negative and positive pressure.
The movable actuating device (6) may be a pipetting robot, in principle, most commercially available type can be incorporated into the system.
Method for dispensing and collecting liquids ln a second aspect, the present invention provides a method for dispensing and collecting liquids using a liquid media handling system (1) according to the first aspect.
The method ofthe second aspect may comprise: a. Reversibly sealing the connecting receptacle (2) with the movable actuatingdevice (6);b. lnserting the connecting receptacle (2) into the receiving element (3) thus forming a reversible seal between the connecting receptacle (2) and the receiving element (3), by way of operating the movable actuating device (6); c. Applying negative pressure to the inside ofthe connecting receptacle (2), thuscollecting liquid from the receiving element (3) or alternatively, applying positivepressure to the inside ofthe connecting receptacle (2), thus dispensing liquid to the receiving element (3); and d. Pulling the connecting receptacle (2) out of the receiving element (3) thusreversing the seal between the receptacle and the receiving element (3), by way of moving the actuating device. 13 The method may further comprise disconnecting the connecting receptacle (2) from the movable actuating device (6).
Connecting receptacle ln a third aspect, the present invention provides a connecting receptacle (2) adapted for use in a liquid media handling system (1) according to the first aspect, comprising a lower end (4) formed to fit into a round receiving element (3) having an internal diameter of0.05 to 10 mm and an upper end (5) adapted for reversibly sealing with a movable actuating device (6) of saidsystem such that the connecting receptacle (2) can be disconnected from the movable actuating device (6);characterized in that the connecting receptacle (2) comprises an elastic sleeve (9) arranged around the lower end (4) ofthe connecting receptacle (2); and the connecting receptacle (2) lower end (4) and the elastic sleeve (9) are configured to forma reversible seal with the receiving element (3) when the connecting receptacle (2) isinserted into the receiving element (3), such that the connecting receptacle (2) can be disconnected from the receiving element (3).
Preferably, the connecting receptacle (2) is configured such that the connecting receptacle(2) can be disconnected from the movable actuating device (6) with a force A in direction X(7), and such that the connecting receptacle (2) can be disconnected from the receivingelement (3) with a force B in direction Y (8), wherein force B is smaller than force A and directions X and Y are opposite.
The lower end (4) of the connecting receptacle (2) preferably has a conical shape to facilitate interfacing the connecting receptacle (2) with the receiving element (3).
The elastic sleeve (9) may comprise any suitable elastic material known in the art. Preferredmaterials are tetrafluoroethylene (TFE) and its polymers, commonly called TeflonW' and Fluon“”', synthetic rubber (elastomers), cork, leather, metal or asbestos. 14 The connecting receptacle (2) may comprise a vent (17) for regulation ofthe internalpressure. This allows for pumping of liquid to the connecting receptacle (2) by external positive pressure, without need for a source (10) of negative pressure in the system itself.
The connecting receptacle (2) is preferably configured to seal with a female micro-Luer or Luer fitting located on the receiving element (3).
The connecting receptacle (2) may comprise a pipette tip, preferably a standard 1 ml pipette tip, a 5 ml pipette tip or equivalent.
The connecting receptacle (2) may further comprise a spring (12) located around andoutside said connecting receptacle (2), configured such that when the connecting receptacle(2) and the receiving element (3) are in contact, the spring (12) is in a compressed statepushing the connecting receptacle and the receiving element (3) apart. The spring (12)facilitates detaching the connecting receptacle (2) from the receiving element (3) but mayalso function as a guide to facilitate inserting the connecting receptacle (2) to the receiving element (3).
Preferably, the connecting receptacle (2) is configured to seal with a female micro-Luer or Luer fitting located on the receiving element (3).Means for preventing flow of liquid The connecting receptacle (2) may further comprise a means (13) for preventing flow of liquid when the connecting receptacle (2) is not sealed to a receiving element (3).
The means (13) for preventing flow of liquid may comprise a valve with a movable magneticvalve element (14) capable of blocking the passage of fluid through the connectingreceptacle (2), located inside the connecting receptacle (2); in such case the system furthercomprises a magnetic element (15) outside ofthe connecting receptacle (2) capable ofshifting the magnetic valve element (14) between a position blocking the passage of fluid through the connecting receptacle (2) and a position not blocking said passage.
The connecting receptacle (2) may comprise a tapering tubular segment (16) housing themagnetic valve element (14), said tubular segment (16) and valve element (14) being shaped and dimensioned such that the valve element (14) can be positioned to either block or allow liquid flow through the tubular segment (16). The tubular segment (16) is preferably conical. The valve element (14) is preferably spherical.
The following specific embodiments are not to be regarded as limiting and features between different embodiments may be combined.
Liquid handling system for the automation of the droplet microfluidics ln this case, a liquid handling robot operating as a media dispenser (an automatedcomputer-controlled pipette) is used to interface with a standard microfluidic dropletgenerating chip. A computer controlled liquid handling robot is equipped with a connectingreceptacle (2) (standard 1 mL disposable pipette) which has at the very end an elastic sleeve(9) (a silicon rubber seal). This element is capable of interfacing directly with a receivingelement (3) (such as the micro Luer fitting that forms the outlet/inlet of a droplet generatingmicrofluidic chip). The seal made from a silicon rubber attached to the end of the pipettingtip seals the connection between the tip and the well ofthe droplet generating chip. Themicrofluidic droplet generating chip can for example be made from plastic, e.g. polycarbonate or similar. ln this manner, a perfectly sealed connection between the pipetting tip and the well ofthedroplet generating chip can be established (even multiple times). Therefore, a negative (orpositive) pressure can be efficiently transferred from a pipette connected to a robot andcontrolled by a computer to the ducts of the microfluidic chip. This way, if the inlets of thedroplet generating chip are connected to the continuous and the dispersed phasereservoirs, a negative pressure is introduced into the microfluidic system, making negative pressure driven droplet generation possible.
The pipette controlled by the robot can thus be used as a negative force generator where asits pipette tip equipped with a rubber seal is also used as a reservoir for the generated emulsion - the droplets.
After the pressure equalizes, the generated droplets that are stored in the tip, can be safelyand without any disruption moved by the robotic arm to another location, for example another droplet generating microfluidic chip (used if needed for the fabrication of double 16 emulsion). Each time, the seal attached to the very end of the pipetting tip ensures a leak- less connection between the pipette and the well ofthe microfluidic element (Figure 1).
Liquid handling system for the automation of microfluidic for zero losses of the precious sample I\/licrofluidics, by definition, allows for working with very small volumes of analyzed samples.ln some cases, the volumes are so small (several ul) that the stored sample can be removedfrom the connecting receptacle (2) -for example, a small pipetting tip - simply by thecapillary forces which appear during the disconnecting act when the receptacle is detached from the receiving element (3) such as a microfluidic chip.
Similar problems appear during a physical transfer of liquid sample by a liquid handlingrobot, when capillary forces may introduce a small leak from a connecting receptacle (2)such as a pipetting tip. ln some cases, even a very small leak from a sample reservoir is not acceptable.
To eliminate any back flow, or simply a leak from the pipetting tip used as a connectingreceptacle (2) in an automated microfluidics system based on a liquid handling robot, amagnetic valve can be introduced. This simple valve composes of two elements - a smallfreely moving magnet placed inside the pipetting tip, and the external magnet, that has tobe located near a place where the stored sample is released. By default, this simple valve isin a closed position by gravity. This means that the small moving magnet locates itself at thebottom of the curvature of the inside of the pipetting tip. To open the valve, a pipetting tipwith the closed magnetic valve has to near an external magnet, that attracts the small freelymoving part ofthe magnetic valve. lfthe positioning ofthe external magnet is correct, thenthe moving magnetic part ofthe valve will be attracted to the external magnet, leaving the opening of the pipetting tip free of any blocking elements.
Once the sample is introduced in to the pipetting tip, to lock the valve the liquid handlingrobot has to actively move the tip from the external magnet, to eliminate the magnetic forces that attract the moving and sealing element of the valve.
To maximize the valving properties and to limit the dead volume of the valve, the moving element ofthe magnetic valve can be shaped accordingly to the shape ofthe curvature of 17 the inside ofthe pipetting tip. lt can also be covered with additional materials, that canincrease its sealing properties (for example water repellent materials - PTFE, silicon rubber, etc).
Thus, a magnetic valve can be used to limit the losses of a very small number of dropletsgenerated with a microfluidic droplet generating chip. Here a small volume of a veryexpensive, and therefore precious samples has been used as a dispersed phase. Only severalpl ofthe final emulsion has been generated. Without the valve, that sample in form of thedroplets would be sucked out of the pipetting tip by the capillary forces the moment the tipwould be disconnected from the droplet generating chip (made for example from PDMS).Having the valve closed during the removal ofthe pipetting tip from the PDMS microfluidicchip, the sample in the tip is locked behind the valve. Any capillary forces derived from themicrofluidic chip that act on the valve act to additionally seal the valve during the act of removal the tip from the chip (Figure 2).
Liquid handling system for the automation and multi-step integration of microfluidic ln this case, a liquid handling robot operating as a media dispenser (an automatedcomputer-controlled pipette) is used together with external pressure sources (syringepumps or pressure boxes) to automate workflows integrating various microfluidic chips. Acomputer controlled liquid handling robot is equipped with a standard 1 mL pipette asconnecting receptacle, which can be readily changed being disposable. The tips have at thevery end an elastic sleeve (9) (a seal, for example a silicon rubber ring) to prevent the leak ofliquids at the interface between the liquid handling robot's pipette and a receiving element (3) of a droplet generating microfluidic chip well -its inlet or outlet.
A custom made, sealed and closed dispersed and continuous phase reservoirs connected tothe external pressure sources through special locking system can be collected and relocatedby the liquid handling robot, just like the pipetting tips, and placed precisely into the inletsof the droplet generating chip. The seal, the element that goes into the well of themicrofluidic chip secures and locks the connection, prevents any leaks. The releasingmechanism of the pipette attached to the robotic arm allows the robot to release itself from both the sample/dispersed and the continuous phase reservoirs. Next, the liquid handling 18 robot collects a sample collecting reservoir (a connecting receptacle) which is a pipetting tipequipped with a seal and a simple magnetic valve as well as a vent, that prevents from the internal pressure to build up inside the reservoir.
This element is then moved by the liquid handling robot and placed inside an outlet (areceiving element (3)) of a microfluidic chip. Once the connection is established andsecured, the process controlled by an external computer triggers a build-up of the pressureinside the custom made dispersed and continues phase reservoirs which are connected tothe external positive pressure sources (for example pressure boxes). Due to the build-up ofthe pressure inside microfluidic channels the progress of droplet generation is initiated andthe sample in form of droplets are collected inside the pipetting tip equipped with the seal,valve and the vent. The vent prevents from pressure build up inside the droplet collectingmodified pipetting tip, allowing the liquid handling system to be used with positive pressure microfluidic workflows.
When the process is finished, the robotic arm can easily remove the sample collectingpipetting tip and transfer the collected sample in form of the emulsion (droplets) intoanother location due to the presence of multi-use seal located at the very end of the tip and the magnetic valve that prevents any leak from the reservoir.
Liquid handling system for the automation of the microfluidics where microfluidic elements are made from a soft rubber - Poly(dimethylsiloxane), PDMS ln this case, a liquid handling robot operating as a media dispenser (an automated computercontrolled pipette) is used to interface with a standard microfluidic droplet generating chipmade from PDMS. Poly(dimethylsiloxane), PDMS is the most common material used inmicrofluidics because of its optical properties and the ability of relatively fast prototyping(paired with photolithography). PDMS a gold standard for microfluidics and Lab-On-Chipdevices, therefore it is useful that the automation of microfluidics based on the liquid handling systems also allows for easy interaction with microfluidic chips made from PDMS.
The interface between the liquid handling robot and the microfluidic chip may be built on astandard pipetting tip as connecting receptacle connected to the pipette which the robot is equipped with. This element may be additionally equipped with a seal at the end of the 19 pipetting tip to secure a sealed connection between the robot's parts and the microfluidicchip (an elastic sleeve). This is not essential for this application, as the material from whichthe chip is made (PDMS) has some sealing properties, but the additional seal made from asilicon rubber ring may add additional layer of protection against any leaks. The presence ofthe seal also allows the same connecting receptacle to interface with other types of receiving elements, improving versatility.
On the other hand, to ease the releasing process the pipette tip may be equipped at itsthinner end with a small spring, that loads itself into a compressed state when the robotestablishes the connection between the tip and the PDMS microfluidic chip and releasestrapped force (ejects the tip) when the liquid handling robotic arm releases the connectionand moves the whole element into another location. This additional ejecting force helps inreleasing the sample collecting pipetting tip from the PDMS chip, eliminating the need for astrong bonding between the chip and the surface on which it is placed. lt also helps inmaintaining a strong and properly sealed connection between the pipetting tip and thepipette/robot itself, eliminating the possibility of losing the collected sample by an accidental disconnection ofthe tip from the pipetting robot.Interface The interface (a connecting receptacle) between movable liquid media dispenser and amicrofluidic chip can be custom made (3D printed or similar) or it can be adapted fromalready existing standardized elements developed for liquid media dispensers (e.g. standardpipette tips). ln the embodiments above a standard 1 mL pipetting tip was used - withdimensions compatible with a standard 1 mL pipette: upper opening: ID ”7.55 mm, OD ”8.70 mm, lower opening: ID ”0.55 mm, OD ”1.1 mm, total height: ”69.55 mm.
Seal The seal (an elastic sleeve) that seals the connection between a movable liquid mediadispenser and at least one well ofthe microfluidic chip can be either located on the movablepart of the system or within the well, as its purpose is to seal the connection between amovable liquid media dispenser and a well and to prevent the liquid or the gas from penetrating the connection.
The seal may be fabricated with any ofthe following materials:tetrafluoroethylene (TFE) and its polymers, commonly by trademarks Teflon and Fluon, synthetic rubber (elastomers), cork, leather, metal or asbestos.
In the cases discussed above, the seal was made from a synthetic rubber tube (Tygon, OD”2.2 mm, ID ”0.76 mm, wall thickness: ”0.72mm). A small element, about ”9 mm long wascut and placed securely on the thinner end ofthe 1 mL pipette tip, in such a way, that one ofthe ends ofthe seal and the thinner end ofthe pipette tip were levelled. The dimensions ofthe seal should be compatible with the dimensions ofthe pipette tip and the dimensions ofthe well that it will be used with (for better performance, the OD ofthe seal should be smaller than the ID ofthe well).
Connection To allow easy disconnection, a spring can be added at the end ofthe interfacial element,properly selected pipette tip that interacts with the microfluidic chip (the well). The spring isplaced at the thinner end of the tip, covering if necessary the seal (when it's used with aplastic chip as well as PDMS). It secures its position on the uprising thickness ofthe pipettetip. The spring's dimensions should be compatible with the dimensions ofthe pipetting tipand the dimensions ofthe well that it will be used with (for better performance, the ID ofthe spring should be higher than the OD ofthe well). In the example above the spring ismade from metal wire, it has ”3.2 mm ID, and is ”18.85 mm long when not loaded. When loaded its length decreases to 3.6 mm.
Magnetic valve To eliminate any unwanted flow ofthe liquids that are being stored or relocated using amovable liquid media dispenser a device that prevents the flow - e.g. a valve - may beadded to a connecting receptacle attached to a movable liquid media dispenser. It may beconstructed with two parts: a movable magnetic element, that sits inside e.g. a pipette tip,acting as a plug and a fixed magnetic element placed near the location where the valve should be activated (e.g. close to the outlet of the microfluidic chip). This fixed magnetic 21 part activates the movement of the plug which prevents the leak from the connecting receptacle. ln the case discussed above a movable magnetic part - the plug - was placed inside 1 mL pipette tip may be a disk magnet 1 mm in diameter and 1 mm in height.
The fixed magnetic element, which activates the movement ofthe plug may be a ring magnet 12 mm in diameter and 1.5 mm height.
Vent An air vent in a reservoir attached to a movable liquid media dispenser is useful when system is used with positive pressure, reducing excess pressure inside. ln the embodiments above, this vent is a small hole ”1 mm in diameter, drilled directly in 1 mL pipette tip about 15 mm below the thicker end ofthe pipette tip.
General The term ”comprising” is to be interpreted as including, but not being limited to. Allreferences are hereby incorporated by reference. The arrangement ofthe presentdisclosure into sections with headings and subheadings is merely to improve legibility and isnot to be interpreted limiting in any way, in particular, the division does not in any waypreclude or limit combining features under different headings and subheadings with each other.

Claims (12)

1. A liquid media handling system (1) for dispensing and collecting liquids to or from a receiving element (3), comprising:an elongated connecting receptacle (2) with a lower end (4) formed to fit into a round receiving element (3) having an internal diameter of0.05 to 10 mm and an upper end (5) adapted for reversibly sealing with a movable actuating device (6) suchthat the connecting receptacle (2) can be disconnected from the movable actuating device (6) with a force A in direction X (7);characterized in that the connecting receptacle (2) comprises an elastic sleeve (9) arranged around the lower end (4) ofthe connecting receptacle (2); the connecting receptacle (2) lower end (4) and the elastic sleeve (9) are configured to forma reversible seal with the receiving element (3) when the connecting receptacle (2) isinserted into the receiving element (3), such that the connecting receptacle (2) can be unsealed from the receiving element (3) with a force B in direction Y (8); andwherein force B is smaller than force A, and directions X and Y are opposite, and wherein the connecting receptacle (2) further comprises a spring (12) located aroundand outside of said connecting receptacle (2), configured such that when the connectingreceptacle (2) and the receiving element (3) have formed a seal, the spring (12) is in a compressed state pushing the connecting receptacle and the receiving element (3) apart.
2. The liquid media handling system (1) according to claim 1, wherein the movable actuatingdevice (6) comprises a source (10) of negative or positive pressure configured tocommunicate with the inside ofthe connecting receptacle (2), when the upper end (5) of the connecting receptacle (2) is sealed with the movable actuating device (6).
3. The liquid media handling system (1) according to any ofthe preceding claims, wherein the system further comprises a guide element (11) configured to align the connecting 23 receptacle (2) and the receiving element (3) to facilitate inserting the connecting receptacle (2) into the receiving element (3).
4. The liquid media handling system (1) according to any of the preceding claims, whereinthe system further comprises a means (13) for preventing flow of liquid when theconnecting receptacle (2) is not sealed to receiving element (3), said means being integrated in the connecting receptacle (2).
5. The liquid media handling system (1) according to claim 4, wherein the means (13) forpreventing flow of liquid comprises a valve with a movable magnetic valve element (14)capable of blocking the passage of fluid through the connecting receptacle (2), located inside the connecting receptacle (2); and the system comprises a magnetic element (15) outside ofthe connecting receptacle (2)capable of shifting the magnetic valve element (14) between a position blocking the passage of fluid through the connecting receptacle (2) and a position not blocking said passage.
6. The liquid media handling system (1) according to claim 5, wherein the connectingreceptacle (2) comprises a tapering tubular segment (16) housing the magnetic valveelement (14), said tubular segment (16) and valve element (14) being shaped anddimensioned such that the valve element (14) can be positioned to either block or allow liquid flow through the tubular segment (16).
7. The liquid media handling system (1) according to any ofthe preceding claims, wherein the connecting receptacle (2) comprises a vent (17) for regulation ofthe internal pressure.
8. A connecting receptacle (2) adapted for use in a liquid media handling system (1) according to any of claims 1 - 7, comprising: a lower end (4) formed to fit into a round receiving element (3) having an internal diameter of0.05 to 10 mm and an upper end (5) adapted for reversibly sealing with a movable actuating device (6) of saidsystem such that the connecting receptacle (2) can be disconnected from the movable actuating device (6); characterized in that 24 the connecting receptacle (2) comprises an elastic sleeve (9) arranged around the lower end (4) ofthe connecting receptacle (2); and the connecting receptacle (2) lower end (4) and the elastic sleeve (9) are configured to forma reversible seal with the receiving element (3) when the connecting receptacle (2) isinserted into the receiving element (3), such that the connecting receptacle (2) can be disconnected from the receiving element (3), and wherein the connecting receptacle (2) further comprises a spring (12) located around and outsidesaid connecting receptacle (2), configured such that when the connecting receptacle (2) andthe receiving element (3) are in contact, the spring (12) is in a compressed state pushing the connecting receptacle and the receiving element (3) apart.
9. The connecting receptacle (2) according to claim 8, wherein the connecting receptacle (2) comprises a vent (17) for regulation ofthe internal pressure.
10. The connecting receptacle (2) according to any of claims 8-9, wherein the connectingreceptacle (2) further comprises a means (13) for preventing flow of liquid when the connecting receptacle (2) is not sealed to a receiving element (3).
11. The connecting receptacle (2) according to claim 10, wherein the means (13) forpreventing flow of liquid comprises a valve with a movable magnetic valve element (14)capable of blocking the passage of fluid through the connecting receptacle (2), located inside the connecting receptacle (2).
12. The connecting receptacle (2) according to any of claims 8-11, wherein the connectingreceptacle (2) comprises a tapering tubular segment (16) housing the magnetic valveelement (14), said tubular segment (16) and valve element (14) being shaped anddimensioned such that the valve element (14) can be positioned to either block or allow liquid flow through the tubular segment (16).
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060263263A1 (en) * 2005-05-19 2006-11-23 Fuji Photo Film Co., Ltd. Fluid feeding system, fluid feeding method and flow channel unit
JP2015199028A (en) * 2014-04-08 2015-11-12 Nok株式会社 Method of injecting liquid into micro-channel
US20160332157A1 (en) * 2014-04-08 2016-11-17 Nok Corporation Attachment for liquid injection and liquid injection method
WO2017051641A1 (en) * 2015-09-25 2017-03-30 Nok株式会社 Attachment structure for pipette or pipette tip and attachment for liquid injection, and attachment for liquid injection
US20170225159A1 (en) * 2014-08-06 2017-08-10 Yantai Ausbio Laboratories Co., Ltd. Reagent Carrier Unit, Adapter and Method for Handling a Reagent Carrier Unit
WO2017199852A1 (en) * 2016-05-20 2017-11-23 Nok株式会社 Liquid injection attachment, and liquid injecting device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060263263A1 (en) * 2005-05-19 2006-11-23 Fuji Photo Film Co., Ltd. Fluid feeding system, fluid feeding method and flow channel unit
JP2015199028A (en) * 2014-04-08 2015-11-12 Nok株式会社 Method of injecting liquid into micro-channel
US20160332157A1 (en) * 2014-04-08 2016-11-17 Nok Corporation Attachment for liquid injection and liquid injection method
US20170225159A1 (en) * 2014-08-06 2017-08-10 Yantai Ausbio Laboratories Co., Ltd. Reagent Carrier Unit, Adapter and Method for Handling a Reagent Carrier Unit
WO2017051641A1 (en) * 2015-09-25 2017-03-30 Nok株式会社 Attachment structure for pipette or pipette tip and attachment for liquid injection, and attachment for liquid injection
WO2017199852A1 (en) * 2016-05-20 2017-11-23 Nok株式会社 Liquid injection attachment, and liquid injecting device

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