EP3356041B1 - Device and method for storing and emptying containers filled with fluid in microfluidic devices - Google Patents
Device and method for storing and emptying containers filled with fluid in microfluidic devices Download PDFInfo
- Publication number
- EP3356041B1 EP3356041B1 EP16760753.0A EP16760753A EP3356041B1 EP 3356041 B1 EP3356041 B1 EP 3356041B1 EP 16760753 A EP16760753 A EP 16760753A EP 3356041 B1 EP3356041 B1 EP 3356041B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- container
- hollow needle
- actuator
- receiving unit
- receiving
- Prior art date
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- 239000007788 liquid Substances 0.000 description 14
- 239000012528 membrane Substances 0.000 description 10
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920000219 Ethylene vinyl alcohol Polymers 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
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- 239000000758 substrate Substances 0.000 description 2
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- 210000001331 nose Anatomy 0.000 description 1
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- 229920003023 plastic Polymers 0.000 description 1
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- 229920002493 poly(chlorotrifluoroethylene) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 239000005023 polychlorotrifluoroethylene (PCTFE) polymer Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
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Images
Classifications
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- 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
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/16—Reagents, handling or storing thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0672—Integrated piercing tool
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
- B01L2300/123—Flexible; Elastomeric
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
- B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
- B01L2400/0683—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
-
- 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
- B01L3/52—Containers specially adapted for storing or dispensing a reagent
- B01L3/523—Containers specially adapted for storing or dispensing a reagent with means for closing or opening
Definitions
- Lab-on-a-chip systems are microfluidic devices in which several functionalities of a macroscopic laboratory are accommodated on a plastic substrate, for example, the size of a credit card, and miniaturized and at least partially automated to run complex biological, diagnostic, chemical or physical processes.
- the liquids and reagents required for this can be introduced into a cartridge of the lab-on-a-chip system during operation or can already be stored on the cartridge.
- microfluidic cartridges are known, in which a foil bag, also called a tubular bag, filled with fluid is stored in front.
- a device for receiving and fluidly contacting a container for a fluid.
- the device comprises a receiving unit for receiving a container, the receiving unit having at least one first hollow needle and at least one fixing element for fixing the received container at a predetermined distance from the first hollow needle.
- the first hollow needle extends in the direction of the received container.
- the fixing element is designed such that when the force exerted on the container in the direction of the first hollow needle or on the receiving unit in the direction of the container exceeds a predetermined threshold value, the fixing of the container with the fixing element is released and thereby a predetermined movement of the receiving unit and the container relative to each other is made possible in such a way that the first hollow needle penetrates an envelope of the container for fluid contacting of the container.
- a microfluidic device can in particular be understood to mean a microfluidic chip, a microfluidic cartridge or a lab-on-a-chip system.
- a container for a fluid can in particular be understood to mean a blister or a tubular bag.
- the container can be at least partially filled with a fluid, for example with liquids or reagents, for processes to be carried out in the device.
- a hollow needle can in particular be understood to mean a needle which at least partially has a channel, preferably along a section of the longitudinal axis of the needle, the channel having at least at one end an opening to an outer region around the needle.
- the device has the advantage that the liquids or reagents required for operation of the device, which are generally designed for long-term stable storage, can be accommodated in the device together with their respective container and can be stored long-term stable until use.
- the container it is not necessary to provide the device itself with special materials which are characterized by adequate barrier properties for long-term stable storage of the fluids or reagents.
- the device according to the invention can also be introduced into a microfluidic device shortly before processing.
- the device can preferably also comprise a plurality of holding units for holding containers, so that a plurality of containers with fluids or reagents necessary for the operation of the device can be held in the device.
- the at least one fixing element comprises a latching lug for latching in part of the casing of the accommodated container.
- the threshold value of the force exerted for a solution of the fixation of the container in the locking lug can be predetermined by designing a width and / or a depth of the locking lug.
- the locking lug can be designed, for example, as a depression or recess in the fixing element or in a surface of the receiving unit.
- the latching lug can be designed, for example, as a depression or recess in a curvature protruding from the fixing element or from a surface of the receiving unit, for example a bead-shaped elevation.
- Shaping at least one fixing element as a latching lug is particularly advantageous when a part of the casing of the container to be received protrudes from the container in relation to an environment of the casing, since this makes it easier to snap into the latching lug of the part.
- This is particularly the case with blister packs which comprise a barrier or sealing film, with at least a part, in particular an end section, of the sealing or barrier film projecting beyond the rest of the blister casing and thus being particularly suitable for latching into the latching lug suitable.
- the receiving unit comprises a second hollow needle, which extends in the direction of the container and which is arranged such that the second hollow needle, when the receiving unit and the container move relative to one another, the sleeve of the container for introducing a fluid pushed into the container.
- a fluidic contacting of the container via the second hollow needle enables a particularly effective emptying of the container, since a fluid introduced into the container via the second hollow needle can displace the fluid upstream in the container from the container into the device via the first hollow needle.
- the fluid introduced into the container via the second hollow needle can be a gas, for example nitrogen, a gas mixture, for example air, or a liquid.
- a liquid that does not mix with the fluid in the container can preferably be used.
- the most complete emptying of the container can be achieved by introducing a fluid through the second hollow needle.
- the receiving unit has a first surface and a second surface and third surface connected to the first surface.
- the second surface and the third surface are each connected to the first surface in such a way that the surfaces delimit a receiving space for the container in a U-shaped manner, the first and / or the second hollow needle extending from the first surface into the receiving space.
- This has the advantage that a container to be accommodated can be fixed in a simple manner via one or more fixing elements arranged on the second surface and / or third surface.
- the second surface and the third surface are preferably designed in such a way that the receiving space tapers in the direction of the first surface.
- Such a taper advantageously has the effect that a movement of a received container in the direction of the first and / or second hollow needle counteracts an increasing resistance as soon as the received container touches the second and the third surface.
- the sealing or barrier film is thereby put under tension, which facilitates penetration of the first or the second hollow needle into the container.
- the second surface has a first fixing element and the third surface has a second fixing element for fixing the accommodated container at the predetermined distance from the first hollow needle, the length of the shortest distance between the first fixing element and the second fixing element is between 0.3 cm and 5 cm, preferably between 0.5 cm and 1 cm. Since blisters are available in various standard sizes, in particular in a standard size, the width of the sealing or barrier film being 0.5-1.5 cm, this development has the advantage that a sealing or barrier film of a blister of the standard size a receptacle of the blister and a fixation by the two fixing elements undergoes a bend and is under tension, which facilitates penetration of the first and / or second hollow needle into the blister.
- the first and / or the second hollow needle comprise a sealing ring arranged around the first and / or second hollow needle.
- a device in particular a microfluidic device, with a device and an actuator is described, at least part of the actuator being movably arranged with respect to the device.
- the actuator is arranged in such a way that when a force is exerted on a part of the actuator in the direction of the device or on the device in the direction of the actuator when the force is exerted, the force exerted is passed on via the part of the actuator to a container accommodated in the receiving unit of the device fixation of the container with the fixing element is released and the predetermined movement of the receiving unit and the container relative to one another takes place via a predetermined movement of the part of the actuator and the device relative to one another.
- the actuator comprises an elastic layer or a flexible membrane which can be pressurized via a channel of the actuator or the device.
- an elastic layer or flexible membrane has the advantage that a transmission of force via the elastic layer to the accommodated container can take place in a particularly uniform manner due to the flexibility of the layer or membrane and over a large contact area between layer or membrane and container, so that the transmitted force or pressure is distributed over a larger area of the container. This reduces the risk of undesired destruction of the casing in the contact area between the actuator and the container.
- the part of the actuator comprises at least one plunger and / or a plunger-shaped and / or plunger-shaped shape.
- the actuator is arranged such that when the force is exerted, at least part of the force acts on a predetermined part of the casing of the container by touching the plunger and / or the plunger-shaped shape and / or the plunger-shaped shape.
- the actuator can be arranged such that the part of the force acts on a protruding part of the casing of the container.
- Such a part of the actuator has the advantage that the force is transferred to the container via a predefined point.
- a force transmission can take place via a force effect of the plunger on a projecting part of the casing of the blister and another part of the casing, in particular the part that delimits the fluid Part of the envelope that can be kept free from the actuator.
- the device comprises an insert element that is arranged between the accommodated container and the actuator for transmitting force to the container.
- the insert element preferably comprising a plunger or stamp-shaped shape, a force exerted by the actuator on the insert element can be transferred in a targeted manner to defined locations of the accommodated container.
- the device comprises a frame element, the frame element framing at least a part of the receiving element and at least a part of the frame element being shaped such that the part of the frame element prevents removal of a received container that exceeds a predetermined size.
- the shape of the part of the frame element determines a minimum size for a container to be accommodated in the receiving unit.
- the elastic layer of the actuator is partially connected to the receiving element and arranged between the receiving element and the frame element in such a way that if the elastic layer extends beyond a predetermined extent in the direction of the frame element, the receiving element in the direction of the received container for a fluid Contacting the container is moved.
- the frame element and the receiving element can thus be moved relative to one another.
- the accommodated container is advantageously moved through the part of the frame element in the direction of the first and / or second hollow needle.
- the frame element can preferably have a U-shape, a space formed by the U-shape being provided for receiving the receiving element.
- the shape of the part of the frame element is preferably in the form of at least one hook, the hook preferably being arranged with respect to a container of larger size in such a way that when the hooks move apart it contacts a protruding part of the casing of the container and, in the event of a continued movement apart, that of the container Movement underlying force at least partially transmits in the direction of the first and / or second hollow needle to the part of the sheath.
- a channel for pressurizing the elastic layer is preferably arranged between the receiving element and the elastic layer, for example in the form of a recess in the receiving element.
- This channel can advantageously produce an overpressure, for example by introducing a fluid into the channel, in order to cause the elastic layer to expand in the direction of the frame element.
- the invention also relates to a system comprising a device according to the invention and a container accommodated in the receiving unit of the devices, the container being at least partially filled with a fluid.
- the invention also relates to a method for receiving and emptying a container. In a first step, the container is received in a receiving unit with at least one first hollow needle and fixed at a predetermined spacing from the first hollow needle by at least one fixing element of the receiving unit.
- a force is exerted on the container in the direction of the first hollow needle or on the receiving unit in the direction of the container, the exerted force exceeding a predetermined threshold value for releasing the fixation of the container.
- the container and the receiving unit are moved towards one another, so that the first hollow needle penetrates an envelope of the container for fluid contacting of the container.
- Figures 1a to 1c show an embodiment of the device 100 for receiving and fluidly contacting a container 10 for a fluid.
- the container 10 is a blister with a sheath 11, the blister 10 being partially filled with a liquid 15 and the sheath 11 of the blister 10 comprising a barrier film 12.
- the liquid 15 can preferably be removed by piercing or tearing open the barrier film 12.
- the blister can have a volume between 100 and 10000 microliters, for example.
- the sleeve 11 and in particular the barrier film 12 can be polymer composites with, for example, polypropylene (PP), polyethylene (PE), cyclo-olefin polymer (COP), cyclo-olefin copolymer (COC), polymer-metal composites with in particular polyethylene terephthalate (PET) / aluminum (AI) / PE, PET / AI / PP, AI / PP, AI / PE or other packaging materials, which represent a diffusion barrier for the liquid 15 contained in the container 10 and a long-term stable storage of the Allow liquid.
- the barrier film 12 can have a thickness between 5 and 1000 micrometers.
- the barrier film 12 preferably also has a barrier layer 13 with an exemplary thickness of 5 to 500 micrometers, which comprises, for example, vapor-deposited aluminum, polychlorotrifluoroethylene, stretched and / or transversely stretched polypropylene film or ethylene-vinyl alcohol copolymer (EVOH).
- a barrier layer 13 with an exemplary thickness of 5 to 500 micrometers, which comprises, for example, vapor-deposited aluminum, polychlorotrifluoroethylene, stretched and / or transversely stretched polypropylene film or ethylene-vinyl alcohol copolymer (EVOH).
- the device 100 can for example be part of a lab-on-a-chip, a microfluidic chip or a microfluidic cartridge.
- the device 10 comprises a receiving unit 200 for receiving the container 10, the receiving unit 200 in this example comprising a first hollow needle 211 and a second hollow needle 212.
- the two hollow needles 211, 212 extend from a first surface 201 of the receiving unit 200.
- the receiving unit 200 further comprises a second surface 202 and a third surface 203 such that the surfaces 201, 202, 203 have a receiving space 220 for the received container 10 U -shaped, the hollow needles 211, 212 partially extend into the receiving space 220.
- the receiving unit 200 can in particular comprise a polymer substrate, for example a thermoplastic such as PC, PP, PE, PMMA, COP, COC, and have a thickness of, for example, 0.5 to 5 mm.
- the receiving unit 200 can be manufactured by milling, injection molding, hot stamping, deep drawing or laser structuring.
- the second side 202 and the third side 203 of the receiving unit 200 comprise a first fixing element 221 and a second fixing element 222, which in this exemplary embodiment are designed in the form of locking lugs.
- a width of the first side 201 is made smaller than a width of the barrier film 12 of the container 10 to be accommodated, so that projecting ends of the barrier film 12 can snap into the two latching noses 221, 222 and thereby the container received at a predetermined distance 250 from the first side 201 and thus is fixed by the two hollow needles 211, 212.
- the locking lugs 221, 222 can be designed as depressions or recesses in the second side 202 and the third side 203.
- the detents 221, 222 can also be designed as depressions or recesses in bulges protruding from the sides 202, 203, for example bead-shaped elevations. This enables the protruding ends of the barrier film 12 to be clipped or wedged into the latches 221, 222, as shown in the sequence of figures 1a, 1b, 1c.
- the predetermined spacing 250 of the received and fixed container 10 in the receiving unit 200 is chosen so that damage to the barrier film 12 by the spaced hollow needles 211, 212 in the event of usual vibrations during storage and transport operations is prevented.
- a spacing 250 of 100 ⁇ m to 2 mm can be selected.
- the first hollow needle 211 and the second hollow needle 212 comprise a sealing ring 215, 216 arranged around the respective hollow needle, in order to prevent the fluid from flowing outside the hollow needles when the barrier film 12 of the container 10 is pierced.
- the barrier film 12 can have an elastic layer 13 with an exemplary thickness of 5 to 500 micrometers, the elasticity of the layer causing an additional sealing effect around the hollow needles 211, 212.
- the elastic layer 13 can comprise a rubber, an elastomer, a thermoplastic elastomer and / or a silicone.
- Figure 1c shows the device 100 with the container 10 as the system 1000 of this exemplary embodiment.
- Figures 2a to 2d show in a development of the embodiment Figure 1 an embodiment of the device 500 according to the invention, which device 100 according to the embodiment Figure 1 and includes an actuator 300.
- the actuator 300 in this exemplary embodiment comprises two L-shaped parts 310, each with a plunger-shaped shape 320 of the respectively longer section of the L-shape, the parts 310 being movably arranged relative to the device 100.
- the L-shape of the parts 310 has the advantage that the force on the parts 310 exerts a force on the projecting ends of the barrier film 12 of the Container 10 can be forwarded.
- the actuator could, for example, also have a shape partially enclosing the container 10, for example a U shape.
- the container 10 is moved further in the direction of the projecting hollow needles 211, 212 via the moving parts of the actuator 310, these pierce the barrier film 12 of the container 10 and fluidic contact is established between the device 100 and the container 10, as in FIG Figure 2b shown.
- a fluid 15 located in the container can then be removed from the container 10 via the first hollow needle 211 and / or the second hollow needle 212.
- the liquid 15 can advantageously be removed from the container 10 via the lower of the two hollow needles 211, 212 with respect to the gravitational field of the earth.
- the first hollow needle 211 is the lower of the two hollow needles 211 and 212, via which liquid 15 is withdrawn.
- the device can comprise a pump 110 connected to the first hollow needle 211.
- a particularly efficient emptying process 10 is achieved if, as indicated in the sequence of figures 1c and 1d, a replacement fluid 16, for example a gas or gas mixture, is introduced into the container via the second hollow needle 212 in order to displace the liquid 15 from the container 10 to be supported by the first hollow needle 211.
- the introduction of the replacement fluid can take place here via a second pump 120 of the device, the second pump 120 being fluidly coupled to the second hollow needle 212 and being able to comprise a reservoir for the replacement fluid.
- the second hollow needle 212 can be connected to an environment around the device 100 or around the device 500, so that when sucking through the first Pump 110 on the first hollow needle 211, air from the environment flows into the container 10 as a replacement fluid via the second hollow needle 212.
- the movable parts 310 of the actuator 300 are preferably designed such that when the container 10 is fluidly contacted with the device 100, the movable parts 310 are positively contacted with the receiving unit 200, so that further force is exerted on the actuator via the receiving unit 200 is forwarded and the container 10 experiences no further force.
- Such form-fitting contacting can take place, for example, through the L-shaped design of the moving parts 310 of the actuator 300.
- the hollow needles can comprise metal.
- Figures 3a to 3c show an alternative development according to the invention of the embodiment Figure 1
- the device 500 according to the invention turns off the device 100 Figure 1 and an actuator 300 with a flexible membrane in the form of an elastic layer 330.
- the membrane 330 can be pressurized via a channel 350 of the actuator 300, so that it expands in the direction of the container 10 accommodated in the receiving unit 200 of the device 100 and transmits the pressure to the container 10 as a force.
- Figure 3b It is shown that, by exerting force on the container 10 through the membrane 330, the container 10 has been released from a fixation with the locking lugs 221, 222 and moved in the direction of the hollow needles 211, 212, so that the hollow needles 211, 212 have the barrier film 12 pierce the container 10. As in Figure 3c shown, the container 10 can then be emptied, for example via the first hollow needle 211.
- Figures 4a and 4b show a development of the embodiment Figure 3 , an insert 400 being arranged between the film 330 of the actuator 300 and the container 10 accommodated in the receiving unit 200.
- the insert 400 can comprise the same materials as the receiving element 200.
- the insert 400 has the advantage that one of the membrane 330 transferred force through the insert part 400 is not transmitted to the entire envelope 11 of the container 10, but only to projecting ends 14 of the barrier film 12. This reduces the risk that the container 10 will deform and the envelope 11 of the container 10 will tear due to an overpressure in the container 10.
- the device 500 according to the invention comprises a device 100, an actuator 300 with an elastic layer 330 and a frame element 450.
- the frame element 450 frames at least a part of the receiving element 200.
- a part 451, 452 of the frame element 450 is shaped such that the part 451, 452 of the frame element 450 prevents the removal of a received container 10, for example a blister, which exceeds a predetermined size.
- the frame element 450 can comprise the same materials as the receiving element 200.
- the elastic layer 330 of the actuator 300 is partially connected to the receiving element 200 and arranged between the receiving element 200 and the frame element 450 in such a way that if the elastic layer 330 extends beyond a predefined extent in the direction of the frame element 450, the receiving element 200 in the direction of the Received container 10 is moved for fluidic contacting of the container 10, as indicated in the sequence of figures 5a to 5b.
- the frame element 450 and the receiving element 200 can thus be moved relative to one another.
- the accommodated container 10 is advantageously moved through the part 451, 452 of the frame element 450 in the direction of the first and second hollow needles 211, 212.
- the first and second hollow needles 211, 212 are connected to a first channel 213 and to a second channel 214, respectively, the channels 213, 214 in Figure 5 protrude from the image plane.
- the membrane 330 can be at least partially arranged between the receiving element 200 and a substrate layer 340.
- the shape of the part 451, 452 of the frame element 450 is in the form of a first hook 451 and a second hook 452, the hooks 451, 452 preferably being arranged with respect to a blister 10 that exceeds the size, in such a way that the Moving the hooks apart contacts a projecting part of the sheath 11, namely in each case a projecting end 14 of the barrier film 12 of the blister 10 and, in the event of a continued movement apart, at least partially transmits the force underlying the movement apart in the direction of the first and second hollow needles 211, 212 to the ends 14 ,
- a channel 210 for pressurizing the elastic is preferably arranged between the receiving element 200 and the elastic layer 330, for example in the form of a recess 210 in the receiving element 200.
- an excess pressure can be caused by this channel 210, for example by introducing a fluid into the channel 210, are generated in order to cause the elastic layer 330 to expand in the direction of the frame element 450 for fluidic contacting of the blister 10, as from Figure 5b seen.
- Figure 6 shows a flowchart of an exemplary embodiment of the method 800 according to the invention.
- a container is received in a receiving unit with at least one first hollow needle and fixed at a predetermined spacing from the first hollow needle by at least one fixing element of the receiving unit.
- a force is exerted on the container in the direction of the first hollow needle or on the receiving unit in the direction of the first container, the exerted force exceeding a predetermined threshold value for releasing the fixation of the container.
- the container and the receiving unit are moved towards one another in such a way that the first hollow needles penetrate a casing of the container for fluid contacting of the container.
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Description
Lab-on-a-chip-Systeme sind mikrofluidische Vorrichtungen, in denen mehrere Funktionalitäten eines makroskopischen Labors auf einem beispielsweise kreditkartengroßen Kunststoffsubstrat untergebracht sind und komplexe biologische, diagnostische, chemische oder physikalische Prozesse miniaturisiert und zumindest teilweise automatisiert ablaufen können. Die dafür benötigten Flüssigkeiten und Reagenzien können dabei während des Betriebs in eine Kartusche des Lab-on-a-chip-Systems eingebracht oder bereits auf der Kartusche vorgelagert werden.Lab-on-a-chip systems are microfluidic devices in which several functionalities of a macroscopic laboratory are accommodated on a plastic substrate, for example, the size of a credit card, and miniaturized and at least partially automated to run complex biological, diagnostic, chemical or physical processes. The liquids and reagents required for this can be introduced into a cartridge of the lab-on-a-chip system during operation or can already be stored on the cartridge.
Aus
Beschrieben wird eine Vorrichtung, insbesondere eine mikrofluidische Vorrichtung, zur Aufnahme und fluidischen Kontaktierung eines Behälters für ein Fluid. Die Vorrichtung umfasst eine Aufnahmeeinheit zur Aufnahme eines Behälters, wobei die Aufnahmeeinheit mindestens eine erste Hohlnadel und mindestens ein Fixierungselement für eine Fixierung des aufgenommenen Behälters in einem vorgegebenen Abstand von der ersten Hohlnadel aufweist.A device, in particular a microfluidic device, for receiving and fluidly contacting a container for a fluid is described. The device comprises a receiving unit for receiving a container, the receiving unit having at least one first hollow needle and at least one fixing element for fixing the received container at a predetermined distance from the first hollow needle.
Die erste Hohlnadel erstreckt sich in Richtung des aufgenommenen Behälters. Das Fixierungselement ist derart ausgebildet, dass bei einer einen vorgegebenen Schwellwert überschreitenden Kraftausübung auf den Behälter in Richtung der ersten Hohlnadel oder auf die Aufnahmeeinheit in Richtung des Behälters die Fixierung des Behälters mit dem Fixierungselement gelöst wird und dadurch eine vorgegebene Bewegung der Aufnahmeeinheit und des Behälters relativ zueinander derart ermöglicht wird, dass die erste Hohlnadel eine Hülle des Behälters für eine fluidische Kontaktierung des Behälters durchdringt.
Unter eine mikrofluidischen Vorrichtung kann insbesondere ein mikrofluidischer Chip, eine mikrofluidische Kartusche oder ein Lab-on-a-chip-System verstanden werden. Unter einem Behälter für ein Fluid kann insbesondere ein Blister oder ein Schlauchbeutel verstanden werden. Der Behälter kann zumindest teilweise mit einem Fluid, beispielsweise mit Flüssigkeiten oder Reagenzien, für in der Vorrichtung durchzuführende Prozesse befüllt sein. Unter einer Hohlnadel kann insbesondere eine Nadel verstanden werden, die zumindest teilweise einen Kanal aufweist, vorzugsweise entlang eines Abschnitts der Längsachse der Nadel, wobei der Kanal zumindest an einem Ende eine Öffnung zu einem Außenbereich um die Nadel aufweist.The first hollow needle extends in the direction of the received container. The fixing element is designed such that when the force exerted on the container in the direction of the first hollow needle or on the receiving unit in the direction of the container exceeds a predetermined threshold value, the fixing of the container with the fixing element is released and thereby a predetermined movement of the receiving unit and the container relative to each other is made possible in such a way that the first hollow needle penetrates an envelope of the container for fluid contacting of the container.
A microfluidic device can in particular be understood to mean a microfluidic chip, a microfluidic cartridge or a lab-on-a-chip system. A container for a fluid can in particular be understood to mean a blister or a tubular bag. The container can be at least partially filled with a fluid, for example with liquids or reagents, for processes to be carried out in the device. A hollow needle can in particular be understood to mean a needle which at least partially has a channel, preferably along a section of the longitudinal axis of the needle, the channel having at least at one end an opening to an outer region around the needle.
Die Vorrichtung hat den Vorteil, dass für einen Betrieb der Vorrichtung notwendige Flüssigkeiten oder Reagenzien, welche in der Regel für eine langzeitstabile Lagerung ausgelegt sind, gemeinsam mit ihrem jeweiligen Behälter in die Vorrichtung aufgenommen und bis zu einer Verwendung langzeitstabil gelagert werden können. Durch die Aufnahme des Behälters ist es nicht erforderlich, die Vorrichtung selbst mit speziellen Materialien zu versehen, welche sich für eine langzeitstabile Lagerung der Fluide oder Reagenzien durch ausreichende Barriereeigenschaften auszeichnen. Ferner ist vorteilhaft, dass durch die Aufnahme von Fluiden und Reagenzien samt ihrer Behältnisse eine Vielzahl von unterschiedlichen Fluiden in dieselbe Aufnahmeeinheit aufgenommen werden können, da eine langzeitstabile Lagerung durch die mitaufgenommenen Behälter gewährleistet ist. Mit anderen Worten muss keine speziell eingerichtete Vorlagerungskammer in der Vorrichtung vorgesehen werden, welche Anforderungen für eine langzeitstabile Lagerung unterschiedlicher Fluide oder unterschiedlicher Reagenzien erfüllen muss. Von besonderem Vorteil ist auch, dass eine Entleerung des aufgenommenen Behälters erst unmittelbar vor einer Prozessierung durch eine fluidische Kontaktierung mit der ersten Hohlnadel erfolgen kann. Ferner ist von Vorteil, dass die erfindungsgemäße Vorrichtung mit oder ohne aufgenommenen Behälter auch erst kurz vor einer Prozessierung in eine mikrofluidische Vorrichtung eingeführt werden kann.
Vorzugsweise kann die Vorrichtung auch mehrere Aufnahmeeinheiten zur Aufnahme von Behältern umfassen, so dass mehrere Behälter mit für einen Betrieb der Vorrichtung notwendigen Fluiden oder Reagenzien in der Vorrichtung aufgenommen werden können.The device has the advantage that the liquids or reagents required for operation of the device, which are generally designed for long-term stable storage, can be accommodated in the device together with their respective container and can be stored long-term stable until use. By accommodating the container, it is not necessary to provide the device itself with special materials which are characterized by adequate barrier properties for long-term stable storage of the fluids or reagents. It is also advantageous that a large number of different fluids can be accommodated in the same receptacle unit due to the inclusion of fluids and reagents together with their containers, since long-term stable storage is ensured by the containers which are also accommodated. In other words, no specially designed pre-storage chamber has to be provided in the device, which has to meet the requirements for long-term stable storage of different fluids or different reagents. From Another particular advantage is that the container received can only be emptied immediately before processing by means of fluidic contact with the first hollow needle. It is also advantageous that the device according to the invention, with or without a container, can also be introduced into a microfluidic device shortly before processing.
The device can preferably also comprise a plurality of holding units for holding containers, so that a plurality of containers with fluids or reagents necessary for the operation of the device can be held in the device.
In einer vorteilhaften Ausgestaltung der Vorrichtung umfasst das mindestens eine Fixierungselement eine Rastnase zum Einrasten eines Teils der Hülle des aufgenommenen Behälters. Dies ist besonders vorteilhaft, da durch eine Ausgestaltung einer Breite und/oder eine Tiefe der Rastnase der Schwellwert der Kraftausübung für eine Lösung der Fixierung des Behälters in der Rastnase vorgegeben werden kann. Die Rastnase kann dabei beispielsweise als Vertiefung oder Ausnehmung in dem Fixierungselement oder in einer Fläche der Aufnahmeeinheit ausgeführt sein. Ferner kann die Rastnase beispielsweise als Vertiefung oder Ausnehmung in einer aus dem Fixierungselement oder aus einer Fläche der Aufnahmeeinheit hervorstehenden Wölbung, beispielsweise einer wulstförmigen Erhebung, ausgeführt sein. Dies unterstützt vorteilhafterweise ein Einklipsen oder Einkeilen des Teils der Hülle in die Rastnasen.
Eine Ausformung mindestens eines Fixierungselements als Rastnase ist insbesondere dann von Vorteil, wenn ein Teil der Hülle des aufzunehmenden Behälters bezogen auf eine Umgebung der Hülle vom Behälter absteht, da hierdurch ein Einrasten in die Rastnase des Teils erleichtert ist. Dies ist insbesondere bei Blisterverpackungen der Fall, welche eine Barriere- oder Siegelfolie umfassen, wobei zumindest ein Teil, insbesondere ein Endabschnitt, der Siegel- bzw. Barrierefolie über die restliche Hülle des Blisters hinaussteht und sich damit in besonderer Weise für ein Einrasten in die Rastnase eignet.In an advantageous embodiment of the device, the at least one fixing element comprises a latching lug for latching in part of the casing of the accommodated container. This is particularly advantageous since the threshold value of the force exerted for a solution of the fixation of the container in the locking lug can be predetermined by designing a width and / or a depth of the locking lug. The locking lug can be designed, for example, as a depression or recess in the fixing element or in a surface of the receiving unit. Furthermore, the latching lug can be designed, for example, as a depression or recess in a curvature protruding from the fixing element or from a surface of the receiving unit, for example a bead-shaped elevation. This advantageously supports clipping or wedging the part of the casing into the latching lugs.
Shaping at least one fixing element as a latching lug is particularly advantageous when a part of the casing of the container to be received protrudes from the container in relation to an environment of the casing, since this makes it easier to snap into the latching lug of the part. This is particularly the case with blister packs which comprise a barrier or sealing film, with at least a part, in particular an end section, of the sealing or barrier film projecting beyond the rest of the blister casing and thus being particularly suitable for latching into the latching lug suitable.
In einer vorteilhaften Weiterbildung der Vorrichtung umfasst die Aufnahmeeinheit eine zweite Hohlnadel, welche sich in Richtung des Behälters erstreckt und welche derart angeordnet ist, dass die zweite Hohlnadel bei der vorgegebenen Bewegung der Aufnahmeeinheit und des Behälters relativ zueinander die Hülle des Behälters für ein Einleiten eines Fluids in den Behälter durchdrängt. Durch eine fluidische Kontaktierung des Behälters über die zweite Hohlnadel ist eine besonders effektive Entleerung des Behälters möglich, da ein über die zweite Hohlnadel in den Behälter eingeleitetes Fluid das im Behälter vorgelagerte Fluid über die erste Hohlnadel aus dem Behälter in die Vorrichtung verdrängen kann. Beispielsweise kann das über die zweite Hohlnadel in den Behälter eingeführte Fluid ein Gas, beispielsweise Stickstoff, ein Gasgemisch, beispielsweise Luft, oder eine Flüssigkeit sein. Im Falle einer Flüssigkeit kann vorzugsweise eine Flüssigkeit verwendet werden, die sich nicht mit dem im Behälter befindlichen Fluid mischt. Insbesondere kann durch das Einleiten eines Fluids über die zweite Hohlnadel eine möglichst vollständige Entleerung des Behälters erreicht werden.In an advantageous development of the device, the receiving unit comprises a second hollow needle, which extends in the direction of the container and which is arranged such that the second hollow needle, when the receiving unit and the container move relative to one another, the sleeve of the container for introducing a fluid pushed into the container. A fluidic contacting of the container via the second hollow needle enables a particularly effective emptying of the container, since a fluid introduced into the container via the second hollow needle can displace the fluid upstream in the container from the container into the device via the first hollow needle. For example, the fluid introduced into the container via the second hollow needle can be a gas, for example nitrogen, a gas mixture, for example air, or a liquid. In the case of a liquid, a liquid that does not mix with the fluid in the container can preferably be used. In particular, the most complete emptying of the container can be achieved by introducing a fluid through the second hollow needle.
Gemäß einer vorteilhaften Weiterbildung der Vorrichtung weist die Aufnahmeeinheit eine erste Fläche und eine jeweils mit der ersten Fläche verbundene zweite Fläche und dritte Fläche auf. Die zweite Fläche und die dritte Fläche sind jeweils mit der ersten Fläche derart verbunden, dass die Flächen einen Aufnahmeraum für den Behälter U-förmig begrenzen, wobei sich die erste und/oder die zweite Hohlnadel von der ersten Fläche in den Aufnahmeraum erstrecken. Dies hat den Vorteil, dass ein aufzunehmender Behälter in einfacher Weise über ein oder mehrere auf der zweiten Fläche und/oder dritten Fläche angeordneten Fixierungselemente fixiert werden kann.
Vorzugsweise sind die zweite Fläche und die dritte Fläche derart ausgebildet, dass sich der Aufnahmeraum in Richtung der ersten Fläche verjüngt. Durch eine solche Verjüngung wird vorteilhafterweise erreicht, dass eine Bewegung eines aufgenommenen Behälters in Richtung der ersten und/oder zweiten Hohlnadel ein ansteigender Widerstand entgegenwirkt, sobald der aufgenommene Behälter die zweite und die dritte Fläche berührt. Insbesondere bei einem Blister als Behälter wird dadurch die Siegel- bzw. Barrierefolie unter Spannung gesetzt, was ein Eindringen der ersten oder der zweiten Hohlnadel in den Behälter erleichtert.According to an advantageous development of the device, the receiving unit has a first surface and a second surface and third surface connected to the first surface. The second surface and the third surface are each connected to the first surface in such a way that the surfaces delimit a receiving space for the container in a U-shaped manner, the first and / or the second hollow needle extending from the first surface into the receiving space. This has the advantage that a container to be accommodated can be fixed in a simple manner via one or more fixing elements arranged on the second surface and / or third surface.
The second surface and the third surface are preferably designed in such a way that the receiving space tapers in the direction of the first surface. Such a taper advantageously has the effect that a movement of a received container in the direction of the first and / or second hollow needle counteracts an increasing resistance as soon as the received container touches the second and the third surface. In particular in the case of a blister as a container, the sealing or barrier film is thereby put under tension, which facilitates penetration of the first or the second hollow needle into the container.
In einer vorteilhaften Weiterbildung der Vorrichtung weisen die zweite Fläche ein erstes Fixierungselement und die dritte Fläche ein zweites Fixierungselement für die Fixierung des aufgenommenen Behälters in dem vorgegebenen Abstand von der ersten Hohlnadel auf, wobei eine Länge des kürzesten Abstands zwischen dem ersten Fixierungselement und dem zweiten Fixierungselement zwischen 0,3 Zentimeter und 5 Zentimeter, bevorzugt zwischen 0,5 Zentimeter und 1 Zentimeter beträgt. Da Blister in verschiedenen Standardgrößen verfügbar sind, insbesondere in einer Standardgröße, wobei eine Breite der Siegel- bzw. Barrierefolie 0,5 - 1,5 Zentimeter beträgt, hat diese Weiterbildung den Vorteil, dass eine Siegel- bzw. Barrierefolie eines Blisters der Standardgröße bei einer Aufnahme des Blisters und eine Fixierung durch die beiden Fixierungselemente eine Biegung erfährt und unter Spannung steht, wodurch ein Eindringen der ersten und/oder zweiten Hohlnadel in den Blister erleichtert wird.In an advantageous development of the device, the second surface has a first fixing element and the third surface has a second fixing element for fixing the accommodated container at the predetermined distance from the first hollow needle, the length of the shortest distance between the first fixing element and the second fixing element is between 0.3 cm and 5 cm, preferably between 0.5 cm and 1 cm. Since blisters are available in various standard sizes, in particular in a standard size, the width of the sealing or barrier film being 0.5-1.5 cm, this development has the advantage that a sealing or barrier film of a blister of the standard size a receptacle of the blister and a fixation by the two fixing elements undergoes a bend and is under tension, which facilitates penetration of the first and / or second hollow needle into the blister.
Gemäß einer weiteren Ausgestaltung der Vorrichtung umfassen die erste und/oder die zweite Hohlnadel eine um die erste und/oder zweite Hohlnadel angeordneten Dichtring. Dies hat den Vorteil, dass ein Austreten von Fluid aus dem Behälter nach einem Eindringen der ersten und/oder zweiten Hohlnadel um die Einstichstellen an den Außenseiten der Nadeln verhindert wird und somit ein kontrolliertes Entleeren des Fluids durch das Innere der ersten Hohlnadel gewährleistet ist.According to a further embodiment of the device, the first and / or the second hollow needle comprise a sealing ring arranged around the first and / or second hollow needle. This has the advantage that fluid escape from the container after penetration of the first and / or second hollow needle around the puncture points on the outer sides of the needles and thus a controlled emptying of the fluid through the interior of the first hollow needle is ensured.
Beschrieben wird eine nicht-erfindungsgemäße Einrichtung, insbesondere eine mikrofluidische Einrichtung, mit einer Vorrichtung und einem Aktor, wobei zumindest ein Teil des Aktors bezüglich der Vorrichtung beweglich eingerichtet ist. Der Aktor ist derart angeordnet, dass bei einer einen vorgegebenen Schwellwert überschreitenden Kraftausübung auf den Teil des Aktors in Richtung der Vorrichtung oder auf die Vorrichtung in Richtung des Aktors durch eine Weiterleitung der Kraftausübung über den Teil des Aktors auf einen in der Aufnahmeeinheit der Vorrichtung aufgenommenen Behälter eine Fixierung des Behälters mit dem Fixierungselement gelöst wird und die vorgegebene Bewegung der Aufnahmeeinheit und des Behälters relativ zueinander über eine vorgegebene Bewegung des Teils des Aktors und der Vorrichtung relativ zueinander erfolgt. Dies hat den Vorteil, dass für eine Lösung der Fixierung des aufgenommenen Behälters mit den Fixierungselementen eine Kraft nicht direkt auf den Behälter, sondern auf einen Aktor aufgebracht werden kann, der die Kraft entsprechend einer Ausbildung des Aktors auf definierte Stellen des Behälters überträgt. Da über eine Ausformung des Aktors die Kontaktstellen des Aktors mit dem aufgenommenen Behälter definiert werden können, kann über die Ausformung unter Berücksichtigung des vorgegebenen Schwellwerts einer Kraftausübung für eine Lösung des Behälters aus der Fixierung der Fixierungselemente der vorgegebene Schwellwert für die Kraftausübung auf den Teil des Aktors in Richtung der Vorrichtung oder auf die Vorrichtung in Richtung des Aktors festgelegt werden.A device according to the invention, in particular a microfluidic device, with a device and an actuator is described, at least part of the actuator being movably arranged with respect to the device. The actuator is arranged in such a way that when a force is exerted on a part of the actuator in the direction of the device or on the device in the direction of the actuator when the force is exerted, the force exerted is passed on via the part of the actuator to a container accommodated in the receiving unit of the device fixation of the container with the fixing element is released and the predetermined movement of the receiving unit and the container relative to one another takes place via a predetermined movement of the part of the actuator and the device relative to one another. This has the advantage that a force is not direct for a solution of fixing the received container with the fixing elements can be applied to the container, but to an actuator, which transmits the force according to an embodiment of the actuator to defined locations on the container. Since the contact points of the actuator with the received container can be defined by shaping the actuator, the predetermined threshold value for the force exerted on the part of the actuator can be defined using the shaping, taking into account the predetermined threshold value of a force exerted for a solution of the container from the fixing of the fixing elements be set in the direction of the device or on the device in the direction of the actuator.
Erfindungsgemäß umfasst der Aktor eine elastische Schicht oder eine flexible Membran, welche über einen Kanal des Aktors oder der Vorrichtung mit Druck beaufschlagt werden kann. Eine solche elastische Schicht beziehungsweise flexible Membran hat den Vorteil, dass eine Kraftübertragung über die elastische Schicht auf den aufgenommenen Behälter aufgrund der Flexibilität der Schicht bzw. Membran besonders gleichförmig und über eine große Kontaktfläche zwischen Schicht bzw. Membran und Behälter erfolgen kann, so dass die übermittelte Kraft beziehungsweise der übermittelte Druck auf eine größere Fläche des Behälters verteilt wird. Dies verringert die Gefahr eines ungewolltes Zerstörens der Hülle in dem Kontaktbereich zwischen Aktor und Behälter.
Gemäß einer besonders vorteilhaften Weiterbildung der Erfindung umfasst der Teil des Aktors mindestens einen Stössel und/oder eine stösselförmige und/oder stempelförmige Ausformung. Der Aktor ist dabei derart angeordnet, dass bei der Kraftausübung zumindest ein Teil der Kraft über eine Berührung des Stössels und/oder der stösselförmigen Ausformung und/oder der stempelförmigen Ausformung auf einen vorgegebenen Teil der Hülle des Behälters wirkt. Insbesondere kann der Aktor derart angeordnet sein, dass der Teil der Kraft auf einen vorstehenden Teil der Hülle des Behälters wirkt. Ein solcher Teil des Aktors hat den Vorteil, dass die Kraftübertragung auf den Behälter über eine vordefinierte Stelle erfolgt. Insbesondere bei einer Verwendung von Blistern als Behältern kann in dieser Weiterbildung eine Kraftübertragung über eine Kraftwirkung des Stössels auf einen vorstehenden Teil der Hülle des Blisters erfolgen und ein anderer Teil der Hülle, insbesondere der das Fluid begrenzende Teil der Hülle, von einer Krafteinwirkung durch den Aktor freigehalten werden kann.According to the invention, the actuator comprises an elastic layer or a flexible membrane which can be pressurized via a channel of the actuator or the device. Such an elastic layer or flexible membrane has the advantage that a transmission of force via the elastic layer to the accommodated container can take place in a particularly uniform manner due to the flexibility of the layer or membrane and over a large contact area between layer or membrane and container, so that the transmitted force or pressure is distributed over a larger area of the container. This reduces the risk of undesired destruction of the casing in the contact area between the actuator and the container.
According to a particularly advantageous development of the invention, the part of the actuator comprises at least one plunger and / or a plunger-shaped and / or plunger-shaped shape. The actuator is arranged such that when the force is exerted, at least part of the force acts on a predetermined part of the casing of the container by touching the plunger and / or the plunger-shaped shape and / or the plunger-shaped shape. In particular, the actuator can be arranged such that the part of the force acts on a protruding part of the casing of the container. Such a part of the actuator has the advantage that the force is transferred to the container via a predefined point. In this development, in particular when blisters are used as containers, a force transmission can take place via a force effect of the plunger on a projecting part of the casing of the blister and another part of the casing, in particular the part that delimits the fluid Part of the envelope that can be kept free from the actuator.
Gemäß einer bevorzugten Weiterbildung der Erfindung umfasst die Einrichtung ein Einlegeelement, dass für eine Kraftübermittlung auf den Behälter zwischen dem aufgenommenen Behälter und dem Aktor angeordnet ist. Durch eine entsprechende Ausformung des Einlegeelements, wobei das Einlegeelement vorzugsweise eine stössel- oder stempelförmige Ausformung umfasst, kann eine durch den Aktor auf das Einlegeelemente übermittelte Kraftausübung gezielt auf definierte Stellen des aufgenommenen Behälters übertragen werden.According to a preferred development of the invention, the device comprises an insert element that is arranged between the accommodated container and the actuator for transmitting force to the container. By appropriate shaping of the insert element, the insert element preferably comprising a plunger or stamp-shaped shape, a force exerted by the actuator on the insert element can be transferred in a targeted manner to defined locations of the accommodated container.
In einer vorteilhaften Weiterbildung der Erfindung umfasst die Einrichtung ein Rahmenelement, wobei das Rahmenelement zumindest einen Teil des Aufnahmeelements umrahmt und wobei zumindest ein Teil des Rahmenelements derart ausgeformt ist, dass der Teil des Rahmenelements eine Entnahme eines eine vorgegebene Größe überschreitenden aufgenommenen Behälters verhindert. Die Ausformung des Teils des Rahmenelements bestimmt dabei eine Mindestgröße für einen in die Aufnahmeeinheit aufzunehmenden Behälter. Die elastische Schicht des Aktors ist in dieser Weiterbildung teilweise mit dem Aufnahmeelement verbunden und zwischen dem Aufnahmeelement und dem Rahmenelement derart angeordnet, dass bei einer über eine vorgegebene Ausdehnung hinausgehenden Ausdehnung der elastischen Schicht in Richtung des Rahmenelements das Aufnahmeelement in Richtung des aufgenommen Behälters für eine fluidische Kontaktierung des Behälters bewegt wird. In dieser Weiterbildung sind somit das Rahmenelement und das Aufnahmeelement gegeneinander bewegbar. Durch die genannte Ausformung des Teils des Rahmenelements wird bei einer Bewegung des Rahmenelements und des Aufnahmeelements in entgegengesetzten Richtungen voneinander vorteilhafterweise der aufgenommene Behälter durch den Teil des Rahmenelements in Richtung der ersten und/oder zweiten Hohlnadel bewegt. Somit kann durch eine Auseinanderbewegung des Rahmenelements und des Aufnahmeelements die fluidische Kontaktierung des Behälters durch das Aufnahmeelement erreicht werden.In an advantageous development of the invention, the device comprises a frame element, the frame element framing at least a part of the receiving element and at least a part of the frame element being shaped such that the part of the frame element prevents removal of a received container that exceeds a predetermined size. The shape of the part of the frame element determines a minimum size for a container to be accommodated in the receiving unit. In this development, the elastic layer of the actuator is partially connected to the receiving element and arranged between the receiving element and the frame element in such a way that if the elastic layer extends beyond a predetermined extent in the direction of the frame element, the receiving element in the direction of the received container for a fluid Contacting the container is moved. In this development, the frame element and the receiving element can thus be moved relative to one another. As a result of the above-mentioned shaping of the part of the frame element, when the frame element and the receiving element move in opposite directions from one another, the accommodated container is advantageously moved through the part of the frame element in the direction of the first and / or second hollow needle. Thus, by moving the frame element and the receiving element apart, the fluidic contacting of the container can be achieved by the receiving element.
Das Rahmenelement kann vorzugsweise eine U-Form aufweisen, wobei ein durch die U-Form gebildeter Raum zur Aufnahme des Aufnahmeelements vorgesehen ist.
Vorzugsweise ist die Ausformung des Teils des Rahmenelements in Form zumindest eines Hakens ausgebildet, wobei der Haken bevorzugt bezüglich eines die Größe überschreitenden Behälters derart angeordnet ist, dass bei der Auseinanderbewegung der Haken einen vorstehenden Teil der Hülle des Behälters kontaktiert und bei einer fortgesetzten Auseinanderbewegung die der Auseinanderbewegung zugrundeliegende Kraft zumindest teilweise in Richtung der ersten und/oder zweiten Hohlnadel auf den Teil der Hülle überträgt.
Vorzugsweise ist zwischen dem Aufnahmeelement und der elastischen Schicht ein Kanal zur Druckbeaufschlagung der elastischen Schicht angeordnet, beispielsweise in Form einer Ausnehmung in dem Aufnahmeelement. Durch diesen Kanal kann vorteilhafterweise ein Überdruck, beispielsweise durch Einleitung eines Fluids in den Kanal, erzeugt werden, um eine Ausdehnung der elastischen Schicht in Richtung des Rahmenelements zu bewirken.
Die Erfindung betrifft auch ein System umfassend eine erfindungsgemäße Einrichtung und einen in der Aufnahmeeinheit der Vorrichtungen aufgenommenen Behälter, wobei der Behälter zumindest teilweise mit einem Fluid gefüllt ist.
Die Erfindung betrifft ferner auch ein Verfahren zur Aufnahme und Entleerung eines Behälters. In einem ersten Schritt wird der Behälter in eine Aufnahmeeinheit mit mindestens einer ersten Hohlnadel aufgenommenen und in einer vorgegebenen Beabstandung von der ersten Hohlnadel durch mindestens ein Fixierungselement der Aufnahmeeinheit fixiert. In einem zweiten Schritt wird eine Kraft auf den Behälter in Richtung der ersten Hohlnadel oder auf die Aufnahmeeinheit in Richtung des Behälters ausgeübt, wobei die ausgeübte Kraft einen vorgegebenen Schwellwert für ein Lösen der Fixierung des Behälters überschreitet. In einem dritten Schritt werden Behälter und Aufnahmeeinheit aufeinander zubewegt, so dass die erste Hohlnadel eine Hülle des Behälters für eine fluidische Kontaktierung des Behälters durchdringt.The frame element can preferably have a U-shape, a space formed by the U-shape being provided for receiving the receiving element.
The shape of the part of the frame element is preferably in the form of at least one hook, the hook preferably being arranged with respect to a container of larger size in such a way that when the hooks move apart it contacts a protruding part of the casing of the container and, in the event of a continued movement apart, that of the container Movement underlying force at least partially transmits in the direction of the first and / or second hollow needle to the part of the sheath.
A channel for pressurizing the elastic layer is preferably arranged between the receiving element and the elastic layer, for example in the form of a recess in the receiving element. This channel can advantageously produce an overpressure, for example by introducing a fluid into the channel, in order to cause the elastic layer to expand in the direction of the frame element.
The invention also relates to a system comprising a device according to the invention and a container accommodated in the receiving unit of the devices, the container being at least partially filled with a fluid.
The invention also relates to a method for receiving and emptying a container. In a first step, the container is received in a receiving unit with at least one first hollow needle and fixed at a predetermined spacing from the first hollow needle by at least one fixing element of the receiving unit. In a second step, a force is exerted on the container in the direction of the first hollow needle or on the receiving unit in the direction of the container, the exerted force exceeding a predetermined threshold value for releasing the fixation of the container. In a third step, the container and the receiving unit are moved towards one another, so that the first hollow needle penetrates an envelope of the container for fluid contacting of the container.
Ausführungsbeispiele der Erfindung sind in den Zeichnungen schematisch dargestellt und in der nachfolgenden Beschreibung näher erläutert. Für die in den verschiedenen Figuren dargestellten und ähnlich wirkenden Elemente werden gleiche Bezugszeichen verwendet, wobei auf eine wiederholte Beschreibung der Elemente verzichtet wird.Exemplary embodiments of the invention are shown schematically in the drawings and are explained in more detail in the description below. The same reference numerals are used for the elements shown in the various figures and acting in a similar manner, and the elements are not repeated.
-
Figur 1 eine schematische Darstellung eines Ausführungsbeispiels der nicht- erfindungsgemäßen Vorrichtung und eines nicht-erfindungsgemäßen Systems,Figure 1 1 shows a schematic illustration of an exemplary embodiment of the device and a system of the invention, -
Figur 2 schematische Darstellung eines Ausführungsbeispiels einer nicht-erfindungsgemäßen Einrichtung mit einer Vorrichtung sowie eines nicht-erfindungsgemäßen Systems,Figure 2 schematic representation of an embodiment of a device not according to the invention with a device and a system not according to the invention, -
Figuren 3 bis 5 schematische Darstellung von Ausführungsbeispielen der erfindungsgemäßen Einrichtung mit einer Vorrichtung sowie des erfindungsgemäßen Systems undFigures 3 to 5 schematic representation of embodiments of the device according to the invention with a device and the system according to the invention and -
Figur 6 ein Flussdiagramm eines Ausführungsbeispiels des erfindungsgemäßen Verfahrens.Figure 6 a flowchart of an embodiment of the method according to the invention.
Der Blister kann dabei beispielsweise ein Volumen zwischen 100 und 10000 Mikroliter aufweisen. Die Hülle 11 und insbesondere die Barrierefolie 12 können Polymerverbunde mit beispielsweise Polypropylen (PP), Polyethylen (PE), Cyclo-Olefin-Polymer (COP), Cyclo-Olefin-Copolymer (COC), Polymer-Metall-Verbunde mit insbesondere Polyethylenterephthalat (PET)/Aluminium (AI)/PE, PET/AI/PP, AI/PP, AI/PE oder andere Verpackungswerkstoffe umfassen, die eine Diffusionsbarriere für die in den Behälter 10 aufgenommene Flüssigkeit 15 darstellen und eine langzeitstabile Lagerung der Flüssigkeit ermöglichen. Beispielsweise kann die Barrierfolie 12 eine Dicke zwischen 5 und 1000 Mikrometer aufweisen. Vorzugsweise weist die Barrierfolie 12 ferner eine Barriereschicht 13 in einer beispielhaften Dicke von 5 bis 500 Mikrometer auf, welche beispielsweise aufgedampftes Aluminium, Polychlortrifluorethylen, gereckte und/oder in Querrichtung verstreckte Polypropylen-Folie oder EthylenVinylalkohol-Copolymer (EVOH) umfasst.The blister can have a volume between 100 and 10000 microliters, for example. The
Die Vorrichtung 100 kann beispielsweise Teil eines Lab-on-a-chip, eines mikrofluidischen Chips oder einer mikrofluidische Kartusche sein. Die Vorrichtung 10 umfasst eine Aufnahmeeinheit 200 zur Aufnahme des Behälters 10, wobei die Aufnahmeeinheit 200 in diesem Beispiel eine erste Hohlnadel 211 und eine zweite Hohlnadel 212 umfasst. Die beiden Hohlnadeln 211, 212 erstrecken sich aus einer ersten Fläche 201 der Aufnahmeeinheit 200. Die Aufnahmeeinheit 200 umfasst ferner eine zweite Fläche 202 und eine dritte Fläche 203 derart, dass die Flächen 201, 202, 203 einen Aufnahmeraum 220 für den aufgenommenen Behälter 10 U-förmig begrenzen, wobei sich die Hohlnadeln 211, 212 teilweise in den Aufnahmeraum 220 erstrecken. Die Aufnahmeeinheit 200 kann insbesondere ein Polymersubstrat, beispielsweise ein Thermoplast wie PC, PP, PE, PMMA, COP, COC, umfassen und eine Dicke von beispielsweise 0,5 bis 5 mm aufweisen. Die Herstellung der Aufnahmeeinheit 200 kann dabei durch Fräsen, Spritzguss, Heißprägen, Tiefziehen oder Laserstrukturierung erfolgen.The
Die zweite Seite 202 und die dritte Seite 203 der Aufnahmeeinheit 200 umfassen ein erstes Fixierungselement 221 beziehungsweise ein zweites Fixierungselement 222, welche in diesem Ausführungsbeispiel in Form von Rastnasen ausgeführt sind. Eine Breite der ersten Seite 201 ist in diesem Beispiel kleiner als eine Breite der Barrierefolie 12 des aufzunehmenden Behälters 10 ausgeführt, so dass vorstehende Enden der Barrierefolie 12 in die beiden Rastnasen 221, 222 einrasten können und dadurch der aufgenommene Behälter in einem vorgegebenen Abstand 250 von der ersten Seite 201 und somit von den beiden Hohlnadeln 211, 212 fixiert wird. Wie in den
Die vorgegebene Beabstandung 250 des aufgenommenen und fixierten Behälters 10 in der Aufnahmeeinheit 200 wird dabei so gewählt, dass eine Beschädigungen der Barrierefolie 12 durch die beabstandeten Hohlnadeln 211, 212 bei üblichen Erschütterungen während Lager- und Transportvorgängen verhindert werden. Beispielsweise kann eine Beabstandung 250 von 100 µm bis 2 mm gewählt werden. In diesem Beispiel umfassen die erste Hohlnadel 211 und die zweite Hohlnadel 212 einen um die jeweilige Hohlnadel angeordneten Dichtring 215, 216, um bei einem Durchstechen der Barrierefolie 12 des Behälters 10 ein Ausfließen des Fluids außerhalb der Hohlnadeln zu verhindern. Alternativ oder zusätzlich kann die Barrierefolie 12 eine elastische Schicht 13 mit einer beispielhaften Dicke von 5 bis 500 Mikrometer aufweisen, wobei die Elastizität der Schicht eine zusätzliche Dichtwirkung um die Hohlnadeln 211, 212 verursacht. Die elastische Schicht 13 kann einen Gummi, ein Elastomer, ein thermoplastisches Elastomer und/oder ein Silikon umfassen.The
Wenn der Behälter 10 über die beweglichen Teile des Aktors 310 weiter in Richtung der vorstehenden Hohlnadeln 211, 212 bewegt wird, durchstoßen diese die Barrierefolie 12 des Behälters 10 und ein fluidischer Kontakt zwischen der Vorrichtung 100 und dem Behälter 10 ist hergestellt, wie in
Wie aus den
Um ein Durchdringen der Hohlnadeln 211, 212 in den Behälter 10 durch die Barrierefolie 12 zu erleichtern, können die Hohlnadeln Metall umfassen.If the
Like from the
In order to facilitate penetration of the
In diesem Ausführungsbeispiel der Erfindung ist die Ausformung des Teils 451, 452 des Rahmenelements 450 in Form eines ersten Hakens 451 und eines zweiten Hakens 452 ausgebildet, wobei die Haken 451, 452 bevorzugt bezüglich eines die Größe überschreitenden Blisters 10 derart angeordnet ist, dass bei der Auseinanderbewegung die Haken einen vorstehenden Teil der Hülle 11, nämlich jeweils ein vorstehendes Ende 14 der Barrierefolie 12 des Blisters 10 kontaktiert und bei einer fortgesetzten Auseinanderbewegung die der Auseinanderbewegung zugrundeliegende Kraft zumindest teilweise in Richtung der ersten und zweiten Hohlnadel 211, 212 auf die Enden 14 überträgt.In this exemplary embodiment of the invention, the shape of the
Vorzugsweise ist zwischen dem Aufnahmeelement 200 und der elastischen Schicht 330 ein Kanal 210 zur Druckbeaufschlagung der elastischen angeordnet, beispielsweise in Form einer Ausnehmung 210 in dem Aufnahmeelement 200. Durch diesen Kanal 210 kann vorteilhafterweise ein Überdruck, beispielsweise durch Einleitung eines Fluids in den Kanal 210, erzeugt werden, um eine Ausdehnung der elastischen Schicht 330 in Richtung des Rahmenelements 450 für eine fluidische Kontaktierung des Blisters 10 zu bewirken, wie aus
Claims (12)
- Apparatus (500), in particular microfluidic apparatus (550), having a device (100), in particular a microfluidic device (100), for receiving and fluidically contacting a container (10) for a fluid, wherein the device (100) comprises a receiving unit (200) for receiving the container (10), wherein the receiving unit (200) has at least one first hollow needle (211) and at least one fixing element (220) for fixing the received container (10) at a predefined spacing (250) from the first hollow needle (211), wherein the first hollow needle (211) extends in the direction of the received container (10), and wherein the fixing element (220) is formed such that, when an exertion of force on the container (10) in the direction of the first hollow needle (211), or on the receiving unit (200) in the direction of the container (10), exceeds a predefined threshold value, the fixing of the container (10) by way of the fixing element (220) is released, and consequently a predefined movement of the receiving unit (200) and the container (10) relative to one another is made possible such that the first hollow needle (211) penetrates a casing (11) of the container (10) for fluidic contacting of the container (10), wherein the apparatus (500) comprises an actuator (300), wherein at least a part (310) of the actuator (300) is designed so as to be movable in relation to the device (100), wherein the actuator (300) is arranged such that, when an exertion of force on the part (310) of the actuator (300) in the direction of the device (100), or on the device (100) in the direction of the actuator (300), exceeds a predefined threshold value, a fixing of the container (10) by way of the fixing element (220, 221, 222) is released as a result of the exertion of force being passed on via the part (310) of the actuator (300) to a container (10) received in the receiving unit (200) of the device (100), and the predefined movement of the receiving unit (200) and the container (10) relative to one another is realized via a predefined movement of the part (310) of the actuator (300) and the device (100) relative to one another, characterized in that the part (310) of the actuator (300) comprises an elastic layer or a flexible diaphragm (330), which is able to be pressurized via a duct (350) of the actuator (300) or of the device (100).
- Apparatus(500) according to Claim 1, wherein the at least one fixing element (220) comprises a detent nose (221, 222) for the engagement with detent action of a part of the casing (11) of the received container (10).
- Apparatus (500) according to one of the preceding claims, wherein the receiving unit (200) comprises a second hollow needle (212) which extends in the direction of the container (10) and which is arranged such that, during the predefined movement of the receiving unit (200) and the container (10) relative to one another, the second hollow needle (212) penetrates the casing (11) of the container (10) for introduction of a fluid into the container (10).
- Apparatus (500) according to one of the preceding claims, wherein the receiving unit (200) has a first surface (201), and has a second surface (202) and a third surface (203) which are in each case connected to the first surface (201) such that the surfaces (201, 202, 203) delimit a receiving space (220) for the container (10) in a U-shaped manner, wherein the first and/or the second hollow needle (211, 212) extend from the first surface (201) into the receiving space (220) .
- Apparatus (500) according to Claim 4, wherein the second surface (202) and the third surface (203) are formed such that the receiving space (220) tapers in the direction of the first surface (201) .
- Apparatus (500) according to Claim 4 or 5, wherein the second surface (202) has a first fixing element (221), and the third surface (202) has a second fixing element (222), for the fixing of the received container (10) at the predefined spacing (250) from the first hollow needle (211), and wherein a length of the shortest spacing between the first fixing element (221) and the second fixing element (222) is between 0.3 cm and 5 cm, preferably between 0.5 cm and 1.
- Apparatus (500) according to one of the preceding claims, wherein the first and/or the second hollow needle (211, 212) comprise a sealing ring (215, 216) arranged around the first and/or the second hollow needle (211, 212).
- Apparatus (500) according to one of the preceding claims, wherein the part (310) of the actuator (300) comprises at least one ram and/or a ram-like and/or stamp-like formation (320), wherein the actuator (300) is arranged such that, during the exertion of force, at least part (310) of the force acts on a predefined part of the casing (11) of the container (10) via contact of the ram (320) or of the ram-like or stamp-like formation.
- Apparatus (500) according to one of the preceding claims, wherein the apparatus (500) also comprises an insert element (400) which, for transmitting force to the container (10), is arranged between the received container (10) and the actuator (300).
- Apparatus (500) according to one of the preceding claims, wherein the apparatus (500) comprises a frame element (450), wherein the frame element (450) frames at least a part of the receiving element (200), and wherein at least a part (451, 452) of the frame element (450) is formed such that the part (451, 452) of the frame element (450) prevents removal of a received container (10) exceeding a predefined size, and wherein the elastic layer (330) of the actuator (300) is partially connected to the receiving element (200) and is arranged between the receiving element (200) and the frame element (450) such that, during an expansion of the elastic layer (330) in the direction of the frame element (450), which expansion goes beyond a predefined expansion, the receiving element (200) is moved in the direction of the received container (10) for fluidic contacting of the container (10).
- System comprising an apparatus (500) according to one of the preceding claims and a container (10) received in the receiving unit (200) of the device (100), wherein the container (10) is at least partially filled with a fluid (15).
- Method (800) for receiving and emptying a container (10) in an apparatus (500) according to one of Claims 1 to 10, comprising the steps of:• receiving (801) the container (10) in the receiving unit (200), and fixing the container (10) at a predefined spacing (250) from the first hollow needle (211) by way of at least one fixing element (220, 221, 222) of the receiving unit (200)• exerting (802) a force on the container (10) in the direction of the first hollow needle (211), or on the receiving unit (200) in the direction of the container (10), wherein the exerted force exceeds the predefined threshold value for releasing the fixing of the container (10)• moving (803) the container (10) and the receiving unit (200) toward one another such that the first hollow needle (211) penetrates a casing of the container (10) for fluidic contacting of the container (10).
Applications Claiming Priority (2)
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DE102015218665.2A DE102015218665A1 (en) | 2015-09-29 | 2015-09-29 | Apparatus and method for storing and emptying fluid-filled containers in microfluidic devices |
PCT/EP2016/071049 WO2017055039A1 (en) | 2015-09-29 | 2016-09-07 | Device and method for storing and emptying containers filled with fluid in microfluidic devices |
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EP3356041A1 EP3356041A1 (en) | 2018-08-08 |
EP3356041B1 true EP3356041B1 (en) | 2019-12-18 |
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EP16760753.0A Active EP3356041B1 (en) | 2015-09-29 | 2016-09-07 | Device and method for storing and emptying containers filled with fluid in microfluidic devices |
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EP (1) | EP3356041B1 (en) |
DE (1) | DE102015218665A1 (en) |
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WO (1) | WO2017055039A1 (en) |
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GB2572408B8 (en) * | 2018-03-29 | 2022-06-22 | Univ Heriot Watt | Fluidic device |
CN111205966B (en) | 2020-04-18 | 2020-07-21 | 博奥生物集团有限公司 | Sample extraction chip and biological reaction device |
CN111558404B (en) * | 2020-05-12 | 2022-05-10 | 南方科技大学 | Microfluidic chip droplet path planning method, device, equipment and storage medium |
GB202104784D0 (en) * | 2021-04-01 | 2021-05-19 | Osler Diagnostics Ltd | Liquid handling apparatus |
DE102022207608A1 (en) | 2022-07-26 | 2024-02-01 | Robert Bosch Gesellschaft mit beschränkter Haftung | Fluid bar for a microfluidic device, tank for a microfluidic device, microfluidic device and method for operating a microfluidic device |
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DE3938559A1 (en) | 1989-11-21 | 1991-05-23 | Boehringer Mannheim Gmbh | REAGENT STORAGE SYSTEM FOR A MEDICAL ANALYZER |
US5525298A (en) | 1991-04-19 | 1996-06-11 | Olympus Optical Co., Ltd. | Apparatus for taking liquid content for use in analysis out of container |
EP1291659A3 (en) * | 2001-09-06 | 2008-05-21 | Sysmex Corporation | Automatic sample analyzer and its components |
US20070048194A1 (en) * | 2003-07-04 | 2007-03-01 | November Aktiengesellschaft | Use of a disposable container, microfluidic device and method for processing molecules |
US8916348B2 (en) | 2004-05-06 | 2014-12-23 | Clondiag Gmbh | Method and device for the detection of molecular interactions |
WO2007102599A1 (en) | 2006-03-09 | 2007-09-13 | Arkray, Inc. | Method of sampling specimen, test method and dropping pipette and specimen sampler to be used therein |
US20130071944A1 (en) * | 2009-10-05 | 2013-03-21 | Battelle Memorial Institute | Sample preparation disposable devices and sample collection and preparation methods using same |
DE102012222719A1 (en) | 2012-12-11 | 2014-06-12 | Robert Bosch Gmbh | Film bag for storing a fluid and device for providing a fluid |
DE102013215565A1 (en) * | 2013-08-07 | 2015-02-12 | Robert Bosch Gmbh | Device for introducing a liquid sample into a microfluidic system |
WO2015086741A1 (en) | 2013-12-13 | 2015-06-18 | Roche Diagnostics Gmbh | Reagent vessel holder for an analytical instrument, reagent supply system for an analytical instrument and an analytical instrument |
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2015
- 2015-09-29 DE DE102015218665.2A patent/DE102015218665A1/en not_active Ceased
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2016
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WO2017055039A1 (en) | 2017-04-06 |
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