EP3485974A1 - Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide - Google Patents

Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide Download PDF

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Publication number
EP3485974A1
EP3485974A1 EP17202368.1A EP17202368A EP3485974A1 EP 3485974 A1 EP3485974 A1 EP 3485974A1 EP 17202368 A EP17202368 A EP 17202368A EP 3485974 A1 EP3485974 A1 EP 3485974A1
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EP
European Patent Office
Prior art keywords
valve
air
volume
air duct
microdosing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP17202368.1A
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German (de)
English (en)
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EP3485974B1 (fr
Inventor
Peter Molitor
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Eppendorf SE
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Eppendorf SE
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Priority to EP17202368.1A priority Critical patent/EP3485974B1/fr
Priority to PCT/EP2018/081558 priority patent/WO2019096993A1/fr
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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
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • 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
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • 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
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • 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
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • 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
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • B01L3/0217—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids of the plunger pump type
    • 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
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0265—Drop counters; Drop formers using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves
    • 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
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries

Definitions

  • the invention relates to a microdosing device for the metered dispensing and / or recording of fluid samples in the microvolume range, a system comprising such a microdosage device with a pipetting device and a method for metered dispensing and / or receiving fluid samples in the microvolume range.
  • Pipetting devices are hand-held or automated laboratory devices commonly used in medical, biological, biochemical, chemical and other laboratories. They are used in the laboratory for the precise metering and transport of fluid samples with small volumes and the transfer of such volumes between different sample containers.
  • pipetting devices e.g. liquid samples by vacuum in pipette containers, e.g. Pipette tips, sucked in, stored there, and released from the destination at this point.
  • the hand-held pipetting devices include, for example, hand-held pipettes and repeating pipettes, the latter also being referred to as dispensers.
  • a pipette is understood to mean a device in which a sample to be pipetted can be sucked into a pipetting container, in particular a pipette tip, detachably connected to the pipette by means of a movement device which is assigned to the device and may in particular have a piston.
  • the piston is assigned to the device and between the sample to be pipetted and the piston end there is a cushion of air as the pressure-transmitting fluid, which is under a negative pressure when the sample is taken into the pipetting container, through which the sample is sucked into the pipetting container and / / or held in the pipetting container.
  • a dispenser is understood to mean a device in which a volume of a liquid fluid to be pipetted can be sucked into a dispensing container connected to the dispenser, in particular a dispenser tip designed according to the syringe principle, by means of a movement device, which may in particular have a piston, wherein the Movement device is at least partially associated with the pipetting container, for example by the piston is arranged in the pipetting container.
  • the piston end is very close to or in contact with the fluid sample to be pipetted, which is why the dispenser is also referred to as a direct displacement pipette.
  • Pipetting with a displacement element designed as a piston are also referred to as Kolbenhubpipetten.
  • Pipette tips or Dispenserspitzen consist in particular of plastic and can be thrown away as a disposable item after use or replaced by a fresh pipette tip or Dispenserspitze. But they can also consist of metal or glass or have such material. Pipette tips or dispenser tips are available in different sizes for dosing in different volume ranges.
  • the amount of sample delivered by a single actuation may correspond to the amount of sample aspirated into the device.
  • a quantity of sample taken corresponding to a plurality of dispensing quantities is released step by step again.
  • single-channel pipetting devices and multichannel pipetting devices wherein single-channel pipetting devices contain only a single dispensing / receiving channel and multichannel pipetting devices comprise a plurality of dispensing / receiving channels which in particular allow the parallel dispensing or picking up of multiple samples.
  • Examples of hand-held electronic pipetting devices or pipettes are the Eppendorf Xplorer® and the Eppendorf Xplorer® plus of Eppendorf AG, Germany, Hamburg;
  • Examples of hand-held electronic dispensers are the Multipette® E3 and Multipette® E3x from Eppendorf AG, Germany, Hamburg.
  • These devices like the pipetting device according to the present invention, are operated electrically by moving the pipetting movable part, in particular the piston, through an electric motor device of the pipetting device.
  • An example of a pipetting machine is the Eppendorf epMotion®.
  • Pipetting devices are used for dosing and thus the precise measurement of liquid volumes.
  • the systematic and random errors of the dosage can increase considerably. Details on the usual procedure for the determination of errors and for the metering of small volumes, in particular by wall delivery in the container, can be found in DIN EN ISO 8655.
  • the fluid sample as jet or free drop - also referred to as jet Leaves the pipetting container smallest volumes between 0.1 .mu.l and 1.0 .mu.s, in this case preferably combined under the term "microvolumes", can no longer be adequately metered with conventional pipetting devices. Various physical influences are responsible for this.
  • the US9221046B2 describes a pipette having a longitudinally segmented cylinder piston with segments of different diameters and a piston with correspondingly distributed in the longitudinal direction, differently dimensioned closure elements. Due to the different diameters, larger volumes and smaller volumes can be dispensed or picked up precisely.
  • a drop adhering to the outlet opening is delivered jerkily from this pipette by means of a "blowout".
  • the EP0119573A1 describes a dispenser for dispensing microdrops of a laboratory sample.
  • a sample chamber formed as an elastic tube with a nearby outlet opening has an elastic portion which is compressed by the actuation of an electromagnetically driven anchor bolt.
  • the resulting pressure wave acts in the direction of the outlet opening and causes the ejection of a microdrop.
  • the EP0876219B1 describes a pipetting apparatus having a Dispenserspitze and, connected to this via a fluid channel, a valved piston displacer by means of the pipette tip larger volumes can be pipetted, so sucked and deliverable.
  • a pulse generator is arranged which impulses the liquid in the fluid channel to eject a small drop of defined size from the pipette tip.
  • the pulse generator may be an electromagnetic actuator or a piezo element or may have an ultrasonic or heat source.
  • the EP1206966B1 describes a pipetting apparatus for selectively delivering larger volumes or smallest volumes for life science.
  • a cylinder piston closure which can be moved by means of a spindle drive is provided in a piston chamber with a pulse generator, in this case a piezoelectric element.
  • the pulse generator is arranged as part of the cylinder piston between the cylinder piston closure and the piston rod. Drops in the sub-microliter range are delivered precisely metered by the piezo-controlled, abrupt stopping of the piston.
  • the EP1654068B1 describes a micro-dosing device with an elastically deformable fluid line, which connects a liquid reservoir with an outlet opening of the fluid line.
  • a displacer driven by a piezoactuator is arranged, whose longitudinal position and its stroke when pressing on the fluid line defines the liquid volume to be dispensed.
  • the WO2013167594A1 describes a dispensing arrangement for dispensing laboratory samples, with a serving as a liquid reservoir piston displacer for dispensing and receiving liquid by means of a piston movement.
  • a tapered outlet region of the piston chamber can be excited by a pulse generator, which can be driven piezoelectrically, pneumatically, electromagnetically or by means of ultrasound. Taking into account the liquid meniscus measured at the outlet opening by means of a sensor, a drop of the desired volume is released from the outlet opening by means of a pulse.
  • the WO 99/37400 A1 describes a metering device for the nanoliter to microliter range with a pressure chamber, which is delimited by a displacer, which is filled via an inlet connected to a liquid reservoir and which is emptied via an outlet, wherein the discharged in the free jet volume of liquid via the voltage controlled deflection of the displacer is metered by a piezoelectric actuator.
  • a similar dosing also uses the WO 99/10099 A1 .
  • the DE 197 37 173 B4 describes to produce such a free-jet dispenser as a microsystem dosing.
  • EP 1 488 106 B1 describes a dosing with dosing, actuator and actuator membrane, which impinges on a chamber wall to generate a free jet.
  • DE 100 22 398 B4 describes a microdosing system in which a free jet is generated by means of a gas pressure surge and the size of the dispensed metering volume is regulated by gas pressure measurements.
  • the object of the present invention is to provide an efficiently designed microdosing device for precisely generating a microdosage volume of a fluid sample in the form of a microfree jet.
  • the microdosing device according to the invention for producing a microdosage volume of a fluid sample in the form of a microfree jet, comprises: an air duct having a passage opening which connects a first air duct section and a second air duct section of the air duct, the first air duct section having a first opening and the second air duct section a controllable first valve adapted to selectively keep the passage opening of the air passage closed in a first state to provide an overpressure in the first air passage section opposite to the second one Allow air duct section, or to keep open in a second state, and to allow a sudden change from the first to the second state, * wherein the micro-metering device, in particular an electrical control device, esp in particular an electrical control device of the microdosing, is adapted to control the first valve so that the passage opening is opened
  • the sudden opening of the first valve causes a very efficient acceleration of a micro air volume from the first air duct section out into the second air duct section, which in turn causes efficient acceleration of a micro air volume from the second air duct section and the second opening.
  • the microdosing is particularly suitable for producing a Mikrofludijets, in this case also referred to as microfire jet.
  • a microfree jet is a microliter or sub-microliter volume of fluid that leaves the outlet port of a fluid channel or fluid transfer container as a jet or free drop, also referred to as jet.
  • the metering is in particular independent of the process of producing an overpressure in the first air duct section. Since the volume of micro air emerging from the first air duct section determines the size of the dispensed microdosage volume, a precise metering in the microvolume range is possible.
  • the volume of micro-air moved in the micro-dosing device is preferably in the submicroliter range, that is to say smaller than 1 ⁇ l. Accordingly, the microdosage volume delivered by the microdosing device is in the submicroliter range.
  • the microdosage volume generated as a free jet by a microdosing device preferably corresponds substantially to the volume of microfluid, in particular displaced by a displacement element; in particular, the microdosage volume is identical in magnitude to the micro air volume.
  • a total release volume formed by the successive dispensed microdosage volumes can also be greater than 1 ⁇ l, and is preferably in the range of 0.1 ⁇ l to 10.0 ⁇ l, in particular 0.1 ⁇ l to 5.0 ⁇ l, in particular 0.1 ⁇ l to 2.5 ⁇ l, especially 0.1 ⁇ l to 1.5 ⁇ l.
  • an air chamber which is connectable or connected to the first opening
  • a displacement element which is arranged to displace a microvolume (V) of the air chamber
  • a drive to which To drive deflection of the displacement element, whereby in the first state of the first valve, the pressure in the first air duct section can be generated.
  • These components can Part of the microdosing, or may be components of an external device, in particular an external pipetting, the working cone with the first opening is airtight connectable, so that by means of the external pipetting device in the first state of the first valve, the pressure in the first air duct section can be generated. Since the micro air volume (V) is determined precisely by the volume determined by the displacement element, in particular no pressure sensors in the air chamber or in the first air duct section are required in order to achieve precise metering.
  • the pipetting device is preferably an air cushion pipette operating according to the air cushion principle, in particular a commercially available pipette or a dispenser, which can be adapted in particular to control the microdosing device. Examples of such commercially available pipetting devices have been mentioned above.
  • the control of the microdosing device can also be arranged at least partially or completely in the microdosing device, and can in particular be an electrical control device of the microdosing device. By combining it with a conventional pipette, the micro-dosing device can be used very flexibly.
  • the microdosing is designed as a module.
  • the microdosing device preferably has a connection section which can be connected to and detachable from a corresponding connection section of an external pipetting device.
  • This connection is preferably a positive plug and clamp connection, in which in particular the working cone of a pipetting device is inserted into a suitable receiving portion of the microdosing.
  • the control of the microdosing device can take place via a data exchange of the microdosing device with the pipetting device, in particular via a wired or wireless connection with the pipetting device.
  • the control can also take place independently of the pipetting device, and in particular can be integrated into the microdosing device, and can be partly manually controllable.
  • the displacement element is preferably a piston element, in particular a piston element of a commercially available pipetting device.
  • the piston element is preferably designed to displace micro-air volumes and macro-air volumes.
  • a macro air volume is greater than the micro air volume.
  • a macro air volume is in particular such an air volume which can typically be pipetted with conventional commercially available pipetting devices. Accordingly, a macro air volume can in particular be an air volume greater than 2 .mu.l, in particular less than or equal to 10 .mu.l, 50 .mu.l, 100 .mu.l, 300 .mu.l or 500 .mu ..
  • the microdosing device or a pipetting device, which has the displacement element, in particular the piston element, or In the first state of the first valve, the displacement element is configured to displace the micro-air volume (V) and in particular also to set it to displace a macro-air volume in the second state of the first valve.
  • V micro-air volume
  • the microdosing device, and / or a pipetting device which can be connected to the first opening is preferably designed so that the volume of compressed air to be displaced by the displacement element can be selected by the user, in particular by means of a user interface device which may be part of the microdosing device or the pipetting device.
  • the first opening of the microdosing device is preferably connectable to the working cone of a pipetting device so that the desired overpressure can be set in the first air duct section by means of the displacement element or by means of the pipetting device.
  • the micro-metering device may have an opening portion which includes the first opening.
  • the opening portion of the micro-metering device may be hermetically connectable to an opening portion of the air chamber, e.g. by a positive clamping connection.
  • the opening portion of the air chamber may be a working cone of the pipetting device.
  • the first air duct section has a closable third opening which connects the first air duct section to the outside space, and in particular a controllable second valve, which is arranged to open the third opening of the third
  • a controllable second valve which is arranged to open the third opening of the third
  • the first valve in particular also the second valve or at least one further valve of the microdosing device or of the system preferably has in each case preferably: a valve body on which a valve tappet is movably arranged, which is deflectable by means of at least one FGL actuator of the valve.
  • the valve stem is biased in its first state, in particular by a spring element and closes a passage opening, and is in particular deflected in its second state, whereby the passage opening is opened. Due to the electrical activation of the FGL actuator, the valve is controllable. Further details of the valve according to the invention can be derived from the description of the microdosing device according to the invention and its preferred embodiments.
  • the first valve preferably has an electrically controllable actuator.
  • the valve, in particular the actuator is preferably set up for a sudden opening.
  • the actuator is preferably a shape memory alloy (FGL) actuator.
  • the actuator may also be a piezoelectric element, or an electromagnetically operating actuator.
  • the invention is based in particular on results of measurements on valves with actuators of a shape memory alloy, which show that very precisely and efficiently a valve opening and thus a sample discharge according to the free jet principle can be realized with very compact shape memory material actuators.
  • Shape memory alloys show a special behavior known as the shape memory effect due to a phase transition. Below a material-specific critical temperature, an FGL component is in particular in the martensite phase and can already be (apparently) plastically by low forces deform. However, heating up to another critical temperature will restore the original part shape within milliseconds, and the material behaves like a normal metal according to Hooke's Law.
  • the inventors have found that such shape memory material components are particularly suitable for generating a microfluid free jet due to the force-deflection characteristics that can be realized with these components. Preferred embodiments of a shape memory material actuator will be described below.
  • An actuator of the microdosing device is preferably a shape memory material actuator, but may also be an actuator without shape memory material, in particular an electromechanical actuator or a piezoelectric actuator.
  • actuators are used in the context of this invention, which at least partially or completely consist of or have a shape memory alloy (SMA). These are referred to as shape memory material actuators or FGL actuators.
  • SMA shape memory alloy
  • FGL actuators have a particularly high energy density, so that already very compact actuators are suitable for driving the microdosage devices defined here.
  • Another key advantage of using the FGL actuators, particularly over piezoelectric actuators, is that the operation of the FGL actuators can be done at a relatively low voltage, more particularly between 3V and 10V, especially at 5V.
  • the required voltage sources are compact so that the present microdosing devices are particularly suitable for the construction of portable metering devices, in particular pipetting devices and microdosing devices.
  • the shape memory material actuator comprises or consists of a NiTi alloy.
  • a NiTi alloy also known under the trade name Nitinol
  • Nitinol is particularly biocompatible. In particular, it allows changes in shape of up to 8%, which in particular efficiently produce microdosage chambers with displaced micro volumes in the microliter range and in the submicroliter range to let.
  • the shape memory material actuator particularly preferably has an alloy based on TiNiCu. This is particularly fatigue-resistant in comparison to the conventional NiTi and therefore guarantees, in particular, a high reliability of the microdosing over its entire life.
  • the phase transition or switching temperatures of the material can be determined by differential scanning calorimetry (DSC), see FIG.
  • the FGL is in the form of a film which has a thickness of between 5 ⁇ m and 50 ⁇ m, in particular between 10 and 30 ⁇ m, in particular approximately 20 ⁇ m. This allows adjusting the forces and travel paths by adjusting the two-dimensional geometry. The surface, which is very large in relation to the volume, is retained and ensures rapid heat release or resetting of the FGL actuator in the de-energized state.
  • a FGL actuator in elongated form in particular wire-shaped or web-shaped, and in particular made of a FGL film is formed.
  • the ends of the FGL actuator are electrically contacted.
  • An SMA actuator is preferably arranged on the valve such that the load on the SMA actuator is essentially a tensile load.
  • An elongate FGL actuator may be placed in the non-activated form in a curved geometry.
  • the activated shape may have a less curved shape or a straight orientation, in particular the elongated FGL actuator may have a shorter length in the activated, straight shape than in the non-activated, more curved shape.
  • the contraction upon activation may exert a force on a valve lifter when the ends of the actuator are anchored to a base body of the valve.
  • the FGL actuator is preferably arranged so that the radius of curvature is always at least 50 times the diameter perpendicular to the longitudinal direction of the elongate actuator, to avoid the risk of damaging the FGL actuator to reduce.
  • the diameter or the required web width of a web-shaped FGL actuator is preferably adapted to the need for actuating force, which is required for the realization of the desired valve. Force-deflection characteristics of FGL actuators can be determined by means of a tensile tester.
  • the FGL actuator may in particular also be shaped as a spring, in particular helical, spiral or spiral spring. Such a spring may be relaxed in the first position and tensioned in the second position.
  • the valve may have more than one actuator, in particular at least two actuators which are arranged for the deflection of a valve tappet.
  • two FGL actuators can be used.
  • the deflection of the valve stem is effected from a first to a second position, wherein the valve is open in the second position, that opens the passage opening of the air channel.
  • the valve has an actuator device.
  • This preferably has one or more actuators, in particular FGL actuators, in particular exactly two actuators or more than two actuators, in particular FGL actuators.
  • two elongated, in particular web-shaped, preferably film-based, FGL actuators are arranged one above the other, ie cross-shaped or X-shaped, above a displacement element.
  • the intersection of the FGL actuators is preferably located centrally above a support portion of the valve lifter, with the ends of the FGL actuators anchored to a base body of the valve.
  • the FGL actuators are preferably stretched above the support point in such a way that the intersection always forms a point of curvature of the FGL actuator.
  • a shell-like portion of the actuator assembly is formed, through which the actuator assembly centers above the support point and down along the linear direction of movement between the first and second positions directed force generated, which has a correspondingly precise deflection of the valve stem result.
  • connection member may also be designed such that the FGL actuators do not contact each other mechanically and in particular are electrically insulated from one another by the connection member.
  • the actuator device has at least one coupling element in order to connect the at least one actuator, in particular the FGL actuator, with the valve tappet and / or a base body of the valve.
  • the valve tappet is in particular arranged to be movable relative to the base body.
  • An FGL actuator may be connected to the base body by one or more connecting means.
  • an FGL actuator may be coupled to the base body or to a component attached to the base body, e.g. a board of the valve, be materially connected, in particular soldered.
  • An FGL actuator is preferably electrically isolated from the base body and preferably from other FGL actuators and other parts, while preferably its ends are connected to a voltage source.
  • the linear movement of the valve stem is preferably carried out so that the valve stem is moved in its deflection from the first to the second position away from the passage opening, and vice versa, is moved in the return movement in the first position in the direction of the passage opening.
  • the microdosing device or a valve in particular the first and / or the second valve, preferably has a base body.
  • the base body is preferably formed integrally, but can also be designed in several parts. It is preferably made of metal, plastic or ceramic, or has such materials.
  • the base body forms in particular the air duct. It is also preferred that the air duct is formed by at least one tubular component.
  • the valve has a diaphragm, which is deflected in the first state of the valve by a valve stem and the passage opening closes airtight, to allow the formation of the overpressure in the first air duct section relative to the second air duct section.
  • the base body may have a first part that forms the air channel.
  • a second part of the base body may be provided to be connected to the first part.
  • the second part can have at least one guide section or guide channel in order to guide the valve tappet during the deflection and to align it with a longitudinal direction of the valve of the valve.
  • the membrane can be arranged, in particular fastened, in particular be fastened by clamping between the first and second part.
  • the membrane can seal the passage opening and / or can serve in particular as a return element for returning the valve tappet from the second to the first position.
  • the second part, or a board arranged thereon can in particular be designed as a carrier for the actuator device or the one or more actuators, which can be anchored in particular to the second part or the circuit board.
  • valve stem is in particular a piston-like part.
  • shape of the valve stem is preferably adapted to its deflection by means of a guide device.
  • valve tappet may be cylindrical or have one or more cylindrical sections.
  • the valve has a membrane.
  • a membrane serving as a sealing element and / or as a restoring element is preferably made of polydimethylsiloxane (PDMS), in particular flexible or highly flexible PDMS or silicone, or comprises such material.
  • PDMS polydimethylsiloxane
  • the thickness of the membrane is preferably between 50 microns and 500 ⁇ m, preferably between 100 ⁇ m and 300 ⁇ m, preferably between 150 ⁇ m and 250 ⁇ m, and preferably about 200 ⁇ m.
  • the valve has a restoring element, which is elastically deformable and which is tensioned by the deflection, and with which a restoring force is exerted on the valve stem, in order to reset this after the deflection from the first position to the second position.
  • a membrane serving as a sealing element can also serve as a restoring element.
  • the return element is a spring which is arranged between the base body and the valve tappet.
  • the restoring element may be an actuator, which is actuated in particular by the electrical control device.
  • An elastically deformable component in particular a spring, can also be arranged as a drive element of the deflection, which is tensioned by the actuator - in this case, the passage opening, for example, by releasing a latching connection, which holds the valve stem in the first position opened.
  • the microdosing on the third opening which may be formed in particular as a closable bypass channel, which connects the first air duct section with the outside space in the open state, in particular the ambient pressure.
  • the third opening or the bypass channel is used, in particular, for ventilating the first air duct section or for equalizing the pressure of the first air duct section that is fluidically connected to or selectively connectable to the bypass duct.
  • the microdosing device is set up for the repeated delivery of a microdosage volume of a fluid sample.
  • the microdosing device can thus be operated as a dispensing device or in a dispensing mode.
  • a system according to the invention has, in particular, a microdosing device according to the invention and a pipetting device, and / or at least one device, by means of the control device of which the microdosing device, in particular its first and / or second valve, can be controlled.
  • a microdosage device is also adapted to receive a fluid sample by sucking a fluid sample through the displacement element into the fluid transfer container in the second state of the first valve and, if provided: in the first state of the second valve.
  • the microdosing device is preferably designed as a pipetting device, with which a fluid sample can be sucked in and discharged via the fluid channel.
  • the suction can be done by a (conventional) piston element of a hand-held Kolbenhubpipette or air cushion pipette or a dispenser.
  • the micro-metering device is designed so that the displacement element optionally sucks or displaces a micro air volume.
  • a pipetting device in particular a commercial pipetting device provided with the microdosing device for metering and dispensing fluid samples, preferably comprises: a piston chamber, which forms the air chamber, a movable piston arranged in the piston chamber, which forms the displacement element, for sucking Air in the piston chamber and for the delivery of air from the piston chamber, a pipetting channel that connects the piston chamber with the outside of the piston chamber.
  • such a pipetting device is provided with a microdosing device according to the invention, the first opening of which can be connected to the piston chamber and / or the pipetting channel, so that a microdosage volume of a fluid sample can be metered from the pipetting device by means of the microdosing device and delivered to the outside via the pipetting channel in the form of a microfluid jet is.
  • the invention further relates to a pipetting device with a microdosing device according to the invention for generating a microdosage volume of a fluid sample in the form of a microfree jet, comprising an air chamber, a displacement element, in particular a piston element, for deflection between a first position and a second position and for displacing a microvolume of the air chamber is set, wherein the pipetting preferably a Shape memory material actuator which is arranged in particular for deflecting the displacement element, wherein the pipetting device comprises a piston drive, in particular an electric motor which drives the piston element, wherein the air chamber forms the piston chamber for receiving the piston movably disposed within the piston chamber, so in particular Piston and piston chamber in the manner of a conventional Kolbenhubpipette or working in the manner of a conventional dispenser.
  • a first valve operated by means of an FGL actuator allows, in combination with the piston drive, optionally a very precise microdosing or a dosing of larger volumes, as a result of which the pipetting device can be used flexibly.
  • the pipetting device may be configured to perform microvolume uptake and / or compression by means of a movement of the displacement element caused by the FGL actuator.
  • the recording and / or compression of the microvolumes can be effected by the piston drive.
  • the pipetting of in particular larger volumes can take place by means of the piston drive, that is to say be effected by conventional means.
  • the displacement element may in particular be driven by means of a FGL actuator, which may be part of the microdosing device or the pipetting device.
  • microdosing device A typical use of the microdosing device is in the dosing of biological, biochemical, chemical or medical fluid samples in a laboratory.
  • the microdosing device, or the microdosing device or the pipetting device, which has a microdosing device, or an external device preferably has an electrical control device, around which at least one controllable valve, in particular the first and / or the second valve, in particular an actuator or Actuator control. It is in particular an internal control device, if it is not arranged in an external device.
  • the microdosing device preferably has an electrical voltage source, In particular, a battery to supply the actuator or the FGL actuator with energy. Alternatively or additionally, an interface for connecting an external voltage source is provided.
  • An external device or external part is not part of the microdosing device and can in particular be connected or connected to the microdosage device by means of a connection device, eg cable.
  • the control device is preferably configured to control the at least one valve, in particular to effect the deflection of the valve stem from the first position to the second position. It may additionally or alternatively also be set up to control the deflection of the displacement element.
  • the control device is preferably configured so that the actuator exerts a force on the valve tappet, which moves it from the first position to the second position, in particular abruptly accelerates.
  • the actuator is controlled by the control device so that the actuator exerts a force on the valve stem even after the valve stem has reached the second position, in particular abuts against a stop of the base body of the valve.
  • the micro-metering device may comprise an elastically deformable drive element, in particular a spring, which is tensioned by the actuator, in particular elastically compressed or expanded, and which by its relaxation exerts the force on the valve tappet, the latter from the first position to the second position emotional.
  • the valve stem can be releasably fixed in the second position by a fixing device, in particular be locked. It can be provided a triggering device to release the fixation, so that the drive element performs the deflection.
  • the control device is in particular configured to control the deflection of a FGL actuator from the first to the second position.
  • the FGL actuator is electrically contacted, in particular at a first contact point and a second contact point, in order to flow through an electric current between the two contact points of a current that heats the FGL actuator to the shape memory effect (FGE) the Cause deflection.
  • the control device is in particular configured to control the time course and the Amplitude of the voltage applied to the FGL actuator.
  • the control device is adapted to activate the FGL actuator with a very short voltage or current pulse.
  • the time period is preferably a few 10 milliseconds (ms), preferably 1 ms to 100 ms, preferably 10 ms to 100 ms, in particular about 10 ms.
  • ms milliseconds
  • the control device is adapted to control the FGL actuator, in particular after a period of activation, by a pulse width modulation. This is done in particular so that the effective voltage is throttled so far that the switching position or the mechanical stress of the FGL actuator can be kept straight.
  • the control device has in particular an electronic data processing device, in particular a CPU or a microprocessor.
  • the control device can be program-controlled, in particular by means of program parameters, which determine the point in time and / or the type of deflection of the displacement element of the microdosing device. But it is also possible to realize the control of the microdosing by analog-electronic control of the actuator, ie without a data processing device.
  • the microdosing device or the microdosing device or the pipetting device, which has a microdosing device, or an external device, preferably has a user interface device, with which a user controls the electrical control device, in particular by using the program parameters used to control the microdosage device, in particular generating control signals influenced by user input or by, in the case of an analog electronic control, the dispensing or recording of the desired microdosage volume and the generation of the control signals that activate and / or deactivate the actuator of the at least one valve.
  • the user interface device may each have one or more electrical switches, buttons and / or sensors, and may have output devices, eg displays, in particular a display.
  • the control device may have at least one electrical interface with which control signals can be exchanged, in particular being exchangeable with an external device.
  • the control device can be set up to be controlled by an external device, so that the control device, and thus the microdosing device or microdosing device, can be controlled by an external device by means of the electrical interface.
  • the control device can in particular be designed as a control interface between the control device of an external device and at least one microdosing device or a microdosing device.
  • the control interface may include an electrical circuit for applying voltage to at least one actuator of the at least one microdosing device in response to a control signal.
  • the control signal can be generated by an internal control device or an external control device.
  • the voltage supply for at least one actuator from at least one microdosing device can be integrated in the control device or can be realized via the at least one electrical interface.
  • the electrical interface can be designed for transmitting and / or receiving electrical signals, in particular data.
  • the signal exchange can take place via a wired or wireless connection device.
  • an internal control device via an electrical interface with the device, in particular the pipetting device, by means of a connecting device connectable or temporarily connected, this device is referred to as an external device.
  • the external device may be a pipetting device, in particular a portable, hand-held pipetting device or a hand-held pipette or a hand-held dispenser. If the microdosing device is integrated in a piecing device, the pipetting device is not referred to as an external device.
  • the microdosing device or a microdosing device can be an autonomous or autonomously operating device, which in principle can be operated without the intermediary of an external device.
  • the microdosing device can also be designed as a module of an external device.
  • the module is an optional accessory that can be connected to the external device. The module can do this characterized in that it is - in particular exclusively - operated in dependence on the external device or is operable, in particular by a control device of the external device controls the deflection of at least one displacement element of at least one microdosing.
  • the invention further relates to a system for generating a microdosage volume of a fluid sample in the form of a microfree jet, comprising a microdosing device according to the invention and a conventional or designed for controlling the microdosing pipetting device, which serves to generate this pressure in the first air duct section, wherein the first opening of the microdosing is connectable or connected to an air chamber of the pipetting device, which further comprises: a displacement element, which is adapted to displace a microvolume (V) of the air chamber, and a drive to drive the deflection of the displacement element, whereby in the first state of the first valve Overpressure in the first air duct section can be generated.
  • a displacement element which is adapted to displace a microvolume (V) of the air chamber
  • V microvolume
  • the invention further relates to a method for generating a microdosage volume of a fluid sample in the form of a microfree jet by means of a microdosing device, in particular a microdosing device according to the invention, comprising the step (discharge step) that the first valve is controlled so that the passage opening is opened abruptly by means of the first valve whereby, due to the pressure equalization between the first and second air duct section, a micro air volume exits the first air duct section and a micro air volume (V) leaves the air duct through the second opening so that a microdosage volume determined by the microvolume (V) is maintained in the fluid transfer container Fluid sample is displaced and is discharged in the form of a microfine jet from the fluid transfer container in the outer space.
  • the method comprises the steps that by means of a pipetting device which has an air chamber connected to the first opening and a displacement element, by displacing a microvolume (V) in the Air pressure in the first air duct section is made before the discharge step takes place.
  • a pipetting device which has an air chamber connected to the first opening and a displacement element, by displacing a microvolume (V) in the Air pressure in the first air duct section is made before the discharge step takes place.
  • the method may include steps that implement a pipetting operation, i. the delivery of the previously recorded volume of the fluid sample.
  • the method may also include steps that implement a dispensing operation, i. the stepwise delivery of partial volumes of the previously collected volume of the fluid sample.
  • the method according to the invention is applied in particular to a microdosing device which has an air chamber which is connected to the first opening, a displacement element which is arranged to displace a microvolume (V) of the air chamber, and a drive to drive the displacement of the displacement element, whereby in the first state of the first valve, the overpressure in the first air duct section can be generated.
  • a microdosing device which has an air chamber which is connected to the first opening, a displacement element which is arranged to displace a microvolume (V) of the air chamber, and a drive to drive the displacement of the displacement element, whereby in the first state of the first valve, the overpressure in the first air duct section can be generated.
  • the method is particularly applied to a microdosing device in which the first air duct section has a closable third opening connecting the first air duct section to the exterior and a controllable second valve arranged to selectively connect the third opening of the air duct in one first state to keep closed to allow the overpressure in the first air duct section opposite the second air duct section, or to keep it open in a second state, as well as a change from the first to the second state to bring about a pressure equalization in the first air duct section to the outside enable.
  • the method preferably comprises the step of taking a fluid sample, in particular a liquid, eg a liquid laboratory sample, into a fluid transfer container, eg a pipette tip, connected to the microdosing device.
  • a fluid sample in particular a liquid, eg a liquid laboratory sample
  • a fluid transfer container eg a pipette tip
  • the displacement element in particular a piston element, is moved from a first to a second position.
  • the method for receiving the fluid sample by suction preferably provides at least one of the following steps, in particular in this order: that the first and second valves are closed and the displacement element is in the first position; that the first valve is opened to open the passage opening; that the displacement element is moved from the first to the second position; that the first valve and thus the passage opening is closed again.
  • the fluid sample in particular with the desired microdosage volume, is now in the fluid transfer container and is held there by the slight negative pressure / capillary forces in the usual way.
  • the method for dispensing the fluid sample preferably provides at least one of the following steps, in particular in this order: that the displacement element is in the second position and that the first and the second valve are closed (initial situation); that the displacement element is moved to the first position while the valves are closed, whereby the volume of air in the air chamber and in the first air duct section is compressed, so that the overpressure is generated; that the first valve is opened after the displacement element has reached the first position - this immediately relaxes the compressed air and accelerates the fluid sample at maximum speed.
  • the fluid sample having the desired microdosage volume exits the opening of the fluid transfer container.
  • the step is also provided to perform an overstroke of the displacement element in order to perform a "blowout" of the entire remainder of the fluid sample possibly still contained in the fluid transfer container.
  • This is done by further moving (in the same direction of the displacement element that corresponds to the direction of movement from the second to the first position) of the displacement element from the first position to a further delivery position.
  • the overstroke can also be performed the same with the first-mentioned discharge step, this causes a further (higher) acceleration of the fluid sample.
  • the method for receiving the fluid sample by aspiration preferably provides at least one of the following steps, in particular in this order: that the first and second valves are closed and the displacement element is in the first position; that the first valve is opened to open the passage opening; that the displacement element is moved from the first to the second position; that the first valve and thus the passage opening is closed again.
  • the fluid sample in particular with the desired total volume, is now in the fluid transfer container and is held there by the slight negative pressure / capillary forces in the usual way.
  • the total volume includes the dosing volume and an additional volume.
  • a residual volume or a discarding volume can be provided.
  • the residual volume remains in the fluid transfer container after delivery of all partial volumes and ensures that at least the desired partial volume is available even for the last delivery step.
  • the discard stroke serves to generate a first delivery amount according to the discard stroke prior to delivery of the partial volumes according to the free-jet principle, so that the meniscus of the fluid sample at the delivery port of the fluid transfer container is defined in the same way for all subsequent steps - the meniscus can be used at the first delivery, so directly after shooting, be different than after a demolition according to free jet principle.
  • the second position of the displacement element is adjusted in particular to the total volume accordingly.
  • the method for dispensing the fluid sample without providing a knockout preferably provides at least one of the following steps, particularly in this order: that the displacer is in the second position and the first and second valves are closed (initial situation); that the second valve is opened, whereby the first air duct section is ventilated; that the displacement element is moved by the distance of the additional stroke in the direction of the first position, whereby in particular a possible clearance of the drive mechanism is compensated, which drives the displacement element; that the second valve is closed again; that the displacement element is moved by the distance of a desired part volume in the direction of the first position to an intermediate position, thereby the air in the first air duct section is compressed, so that the overpressure is generated; that the first one Valve is opened after the displacement element has reached the intermediate position - this relaxes the compressed air immediately and accelerates the fluid sample at maximum speed, the fluid sample with the desired microdosing partial volume exits from the opening of the fluid transfer container and the first valve is then again closed (delivery of
  • the step is also provided to carry out an overstroke of the displacement element in order to carry out a "blowout" of the entire residual volume of the fluid sample possibly still contained in the fluid transfer container.
  • This is done by further moving (in the same direction of the displacement element that corresponds to the direction of movement from the second to the first position) of the displacement element from the first position to a further delivery position.
  • the method for dispensing the fluid sample preferably provides at least one of the following steps, particularly in this order: the displacement element is in the second position and the first and second valves are closed (initial situation); that the displacement element is moved by the distance of the additional stroke in the direction of the first position to an initial position, thereby the air in the first air duct section is compressed, so that the overpressure is generated, and in particular a possible play of the drive mechanism is compensated, which is the displacement element drives; that the first valve is opened after the displacement element has reached the starting position - thereby the compressed air immediately relaxes and accelerates the fluid sample at maximum speed, the displacement stroke exits the fluid transfer container according to the free-jet principle and the meniscus at its delivery port is defined; that the first valve is closed again; that the displacement element is moved by the distance of a desired part volume in the direction of the first position to an intermediate position, thereby the air in the first air duct section is compressed, so that the overpressure is generated; that the first valve is opened after the displacement element has
  • the step is also provided to carry out an overstroke of the displacement element in order to carry out the dispensing of the last partial volume with the same blowout of a possible small remaining volume of the fluid sample possibly still contained in the fluid transfer container.
  • This is done by further moving (in the same direction of the displacement element that corresponds to the direction of movement from the second to the first position) of the displacement element from the first position to a further delivery position.
  • FIG. 1a shows the micro-dosing device 1, connected on one side with a connecting portion 100, which serves as a working cone and on which a pipette tip 99 is attached, and connected on the other side with a connecting portion 200 of a conventional pipette.
  • the microdosing device 1 serves to generate a microdosage volume of a fluid sample in the form of a microfree jet. It has an air duct 10, which has a passage opening 14, which has a first air duct section 11 and a second air duct section 12 of the air duct 10 combines.
  • the first air duct section 11 has a first opening 21 and the second air duct section 12 has a second opening 22, with which the fluid transfer container 99 containing the fluid sample is connected by a plug-in clamping connection.
  • the microdosing device 1 has a controllable first valve 31, which is adapted to selectively keep the passage opening 14 of the air duct, in a first state, in order to allow an overpressure in the first air duct section 11 with respect to the second air duct section 12, or a second state, to keep it open, and to allow a sudden change from the first to the second state.
  • the microdosing device 1 and the pipetting device form a system according to the invention for generating a microdosage volume of a fluid sample in the form of a microfree jet.
  • the microdosing device has a cable connection 50, which is in particular part of the system 400, by which the valves 31, 32 are respectively connected to the electrical control device of the pipetting device and are thereby controllable by the latter.
  • the pipetting device (not completely shown) has an air chamber connected to the first opening via the connecting portion 200, a displacer configured to displace a microvolume (V) of the air chamber, and a driver to drive the displacement of the displacer to drive, whereby in the first state of the first valve, the pressure in the first air duct section can be generated.
  • the microvolume V is here identical to the microdosage volume to be dispensed during a pipetting procedure.
  • the displacement element of the pipetting device is a piston element adapted for user-selectable displacement of microvolumes and volumes greater than 2 ⁇ l, and in particular less than or equal to 100 ⁇ l.
  • the first opening 21 of the microdosing device 1 can be connected to the working cone 201 of the pipetting device via a plug / clamp connection, so that the desired overpressure can be set in the first air duct section 11 by means of the pipetting device.
  • the microdosing device 1 can also have its own control device (not shown), which operates independently of the control device of the pipetting device.
  • the overpressure in the first air duct section is generated by the pipetting device, and in particular the user manually triggers the opening of the first valve.
  • the micro-metering device may also be designed (not shown) to include the air chamber, e.g. a piston chamber, the displacement element, e.g. a piston element, and / or having the drive with optional drive mechanism.
  • the microdosing device becomes an independent device which can be operated completely independently of an external pipetting device.
  • the electrical control device in particular an electrical control device of the microdosing device, is configured to control the first valve 31 such that the passage opening 14 is opened abruptly by means of the first valve 31, whereby, due to the pressure equalization between the first 11 and second air passage section 12 , a micro air volume exits from the first air duct section 11 and a micro air volume (V) leaves the air duct 10 through the second opening 22 so that a microdosage volume of the fluid sample held in the fluid transfer container 99 is displaced by the micro air volume (V) and in the form of a microfree jet the fluid transfer container is discharged into the outer space.
  • the first air duct section 11 has a closable third opening 23 which connects the first air duct section 11 to the outside space, and a controllable second valve 32 which is adapted to closed the third opening 23 of the air duct 10 selectively, in a first state hold, to allow the overpressure in the first air duct section 11 relative to the second air duct section, or to keep open in a second state, and to enable a change from the first to the second state to bring about a pressure equalization in the first air duct section 11 to the outside.
  • the air duct 10 with its first 11 and second 12 sections is formed in a base body 40 of the microdosing device 1.
  • the air duct 10 extends substantially linear.
  • To realize the passage opening 14 of the air duct is closed at the level of the passage opening 14 by a wall.
  • a bypass section 15 which is formed in the base body, the first portion 11 of the air duct 10 is deflected to the passage opening 14, from there begins the second air duct section 12, which merges via the bypass section 15 back into the linearly extending region.
  • the passage opening 14 can be closed by the membrane 49 when it is pressed against the passage opening 14 by the valve tappet of the first valve 31, which is tensioned by the spring.
  • To open the valve the valve stem is deflected abruptly by means of an actuator device.
  • the actuator device has two crosswise arranged SMA actuators whose crossing point is centered above the valve stem. The activation of these actuators by means of the current controlled by the controller is maintained as long as the opening of the valve is desired or pre
  • the frame Y marks the second valve 32, which serves to ventilate the first air duct section.
  • Fig. 1c a cross-section through a valve is shown which is constructed like the second valve 32.
  • Fig. 1b a cross-section through a valve is shown, which is constructed like the first valve 31.
  • the valves 31, 32 each have, as shown by the valve 31 in Fig. 1b is shown as an example, a valve stem 36a, a valve spring 36b and a clamping pin 36d.
  • the clamp pin is for preload adjustment of the shape memory material actuator 36e.
  • the valve guide 37 is fitted into a recess of the base body, between the valve guide 37 and the base body, the membrane 49 (36 c) is clamped, which is used as a closure element for both valves 31, 32.
  • a cover part 42 covers the valve guide 37 above the base body 40 from, is fixed thereto and serves as an abutment of the spring 36 b, which is clamped between the cover part and the flange of the valve stem 36 a.
  • the board 41 is attached.
  • the FGL actuators are fastened by soldering to deflect on contraction the pin 36d and associated tappet 36a to open the valve.
  • FIG. 1b is the first, closed state of the valve 31 to see, in which the passage opening 14 is closed.
  • Figure 1c is the closed state of the second valve 32 can be seen, in which by means of the membrane 49, the third opening 23, namely the passage opening 23 is closed, which connects the bypass passage 43 connected to the environment with the first air duct section 11.
  • Fig. 3a to 3c show by way of example how a movable element, for example a displacement element or similarly also a valve tappet, can be deflected.
  • the shape memory material actuator is a TiNiCu-based alloy that is even more fatigue-resistant than the conventional NiTi and thus offers advantageous long-term stability and reliability of the shape memory material actuator.
  • the phase transition or switching temperatures of the material are determined by means of differential scanning calorimetry (DSC), see diagram of the Fig. 6 , In this measurement, the phase transition important for the actuation appears as a peak. From the diagram it can be seen that for a switching of the actuator, the temperature of the actuator must be increased to at least 67 ° C; for the reset, the temperature must be lowered again to a maximum of 50 ° C.
  • the shape memory material actuator is in particular in the martensite phase and can already (apparently) plastically deform by small forces.
  • the shape memory material actuator is in the in Fig. 3a shown first position of the movable element.
  • the shape memory material actuator may in particular be arranged in the first position so that it is under a mechanical stress. He can also be relaxed.
  • the critical temperatures of the shape memory material actuator are adjustable by an electric current I flows through the shape memory material actuator.
  • a power supply is provided with which a circuit leading through the shape memory material actuator can optionally be closed for heating ( Fig. 3b ) or for cooling the shape memory material actuator ( Fig. 3a ).
  • a ball 83b 'or a support member 85a' is used between the movable member and the actuator which itself centers under the X-shaped pocket-like curved actuator means 85.
  • FIGS. 3a and 3b show the X-shaped arranged pocket-like formed actuator 85, wherein in Fig. 3a a first position is shown, in which the movable element is held by the restoring element, for example a spring, in the first position, and wherein in Fig. 3b the second position is shown in which the actuator means 85 has been activated and the movable member has been deflected to the second position in the stop.
  • the actuator device 85 has two shape memory material actuators based on a NiCuTi alloy, namely two elongate web-shaped shape memory material actuators produced on the basis of sputtered film, which cross each other, ie X-shaped, centrally above the ball of the movable element 83 '. are arranged.
  • the use of film-based actuators allows adjustment of forces and travel paths by adapting the two-dimensional geometry. The very large in relation to the volume surface is maintained and ensures rapid heat dissipation or provision of the actuator in the de-energized state.
  • the ends of the shape memory material actuators are on the base body 86, 40 and on the board of the microdosing 80 each at the two coupling points 88 (FIG. Fig. 3a anchored).
  • the shape memory material actuator are stretched above the support point so that the intersection 85a each forms a point of curvature of the shape memory material actuator.
  • a shell-like region of the actuator device is formed, by means of which the actuator device centers above the support point and generates a force directed downwardly along the linear direction of movement between the first and second position, which generates a correspondingly precise deflection entails.
  • the two shape memory material actuators may be coupled by a link (not shown). While in Fig. 3a to 3c the movable element 83 'is constructed from cuboidal sections, it can also be shaped differently, in particular with cylindrical sections, as well as with a ball as support surface for the actuator device 85.
  • the membrane 49 is made of highly flexible PDMS of thickness 200 microns and is deflected in the de-energized state of the shape memory material actuators to close the valve opening.
  • the actuators of the actuator device 85 are, for example, in each case applied in pairs to a carrier plate or board with integrated conductor tracks and electrically contacted, see Fig. 3a, 3b ,
  • the electrical control of the shape memory material actuator via an electrical control device which is adapted to simultaneously apply a voltage to both shape memory material actuators and to contract these synchronously.
  • two actuators are connected to a power source via a three-wire cable.
  • a middle wire serves as a common ground electrode.
  • the actuators are activated during operation with a very short voltage or current pulse lasting a few tens of ms, and then the effective voltage is throttled so far by pulse width modulation that the switching position of the shape memory material actuators can be kept straight.
  • the supply voltage is set to 4 V, the duration of the initial voltage pulse to 10 ms, and the pulse width modulation, for example, to a duty cycle of 1/128.
  • the actual switching time is determined, for example, by observing the actuator (or the ball below it) with a high-speed camera.
  • a shape memory material actuator requires less than 2 ms to travel the stroke.
  • the force-deflection characteristics of the FGL actuators can be determined by means of a tensile tester.
  • the control of these methods for operating the module 1 are preferably implemented by a specially set up, in particular programmed, electrical control device 350 (FIG. Fig. 4 ).
  • the control device 350 may be part of the module 1.
  • the controller 350 may be an external device or its component.
  • the control device 350 may be part of a modified pipetting device, in particular a conventional pipetting device supplemented by the control device 350.

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EP17202368.1A 2017-11-17 2017-11-17 Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide Active EP3485974B1 (fr)

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PCT/EP2018/081558 WO2019096993A1 (fr) 2017-11-17 2018-11-16 Dispositif de microdosage pour le dosage de micro-échantillons de fluide

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3838412A1 (fr) * 2019-12-20 2021-06-23 MT.DERM GmbH Dispositif et procédé de distribution d'une quantité de fluide microfluidique de l'ordre du picolitre et du microlitre et appareil portatif permettant de piquer localement une peau humaine ou animale

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WO1999010099A1 (fr) 1997-08-26 1999-03-04 Eppendorf-Netheler-Hinz Gmbh Systeme de microdosage
WO1999037400A1 (fr) 1998-01-22 1999-07-29 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Dispositif de microdosage
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EP1488106B1 (fr) 2002-05-07 2006-06-14 Fraunhofer-Gesellschaft Zur Förderung Der Angewandten Forschung E.V. Module de dosage a jet libre et procede permettant de le produire
EP1654068B1 (fr) 2003-08-14 2007-01-24 Roland Zengerle Dispositif de microdosage et procede de delivrance dosee de liquides
WO2006018617A1 (fr) * 2004-08-16 2006-02-23 The Technology Partnership Plc Dispositif de distribution de liquide
US20060225786A1 (en) * 2005-04-11 2006-10-12 Unaxis International Trading Ltd Method for operating a pneumatic device for the metered delivery of a liquid and pneumatic device
DE102007010412A1 (de) * 2007-02-13 2008-08-14 Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG Vorrichtung und Verfahren zum Dosieren von Flüssigkeiten in gasgefüllte Räume
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WO2013167594A1 (fr) 2012-05-08 2013-11-14 Roche Diagnostics Gmbh Ensemble distributeur
DE102012209314A1 (de) * 2012-06-01 2013-12-05 Albert-Ludwigs-Universität Freiburg Vorrichtung und Verfahren zur Abgabe oder Aufnahme eines Flüssigkeitsvolumens
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EP3838412A1 (fr) * 2019-12-20 2021-06-23 MT.DERM GmbH Dispositif et procédé de distribution d'une quantité de fluide microfluidique de l'ordre du picolitre et du microlitre et appareil portatif permettant de piquer localement une peau humaine ou animale
US11662749B2 (en) 2019-12-20 2023-05-30 Mt.Derm Gmbh Apparatus and method for metered dispensing of a microfluidic amount of fluid in the picoliter and microliter range and hand-held device for locally piercing human or animal skin

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