EP1654068A1 - Dispositif de microdosage et procede de delivrance dosee de liquides - Google Patents
Dispositif de microdosage et procede de delivrance dosee de liquidesInfo
- Publication number
- EP1654068A1 EP1654068A1 EP04764062A EP04764062A EP1654068A1 EP 1654068 A1 EP1654068 A1 EP 1654068A1 EP 04764062 A EP04764062 A EP 04764062A EP 04764062 A EP04764062 A EP 04764062A EP 1654068 A1 EP1654068 A1 EP 1654068A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- volume
- displacer
- fluid
- actuator
- tube
- 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
Links
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Classifications
-
- 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
-
- 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
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
- B01L2300/0838—Capillaries
-
- 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
- B01L2400/04—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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S239/00—Fluid sprinkling, spraying, and diffusing
- Y10S239/12—Flexible outlets
Definitions
- the present invention relates to a microdosing device, to methods for the metered dispensing of liquids and to methods for setting a desired dosing volume range when using a microdosing device according to the invention.
- this contactless methods take a prominent position.
- One class of known methods relies on fast switching valves.
- a suitable valve usually based on magnetic or piezoelectric drives, connected to a media reservoir via a line and built in this pressure.
- the rapid switching of the valve with a switching time of less than 1 ms generates a very large flow for a short time, so that even at high surface tensions the fluid is able to detach itself from the discharge point and impinge on a substrate as a free jet.
- the metered amount can be controlled by the pressure and / or the switching time of the valve.
- FIG. 7 A schematic representation showing a first known approach which is referred to as a syringe-solenoid method. can be drawn is shown in Fig. 7.
- a fluid line 10 is fluidly connected via a fast-switching microsolenoid valve 12 with a tip 14, which may be removable.
- a nozzle opening 16 At the lower end of the tip 14 is a nozzle opening 16.
- the opposite end of the fluid line 10 is connected via a switching valve 18 with a syringe pump 20.
- a fluid reservoir 22 is also connected to the switching valve 18 via a further fluid line 24.
- the switching valve 18 has two switching states. In a first switching state, a pumping chamber 26 of the syringe pump 20 is fluidly connected to the fluid reservoir 22 via the fluid line 24, so that fluid 28 can be sucked from the fluid reservoir into the pumping chamber 26 by moving the volume of the pumping chamber 26 by a corresponding movement of the pumping chamber Piston 30 of the syringe pump is increased. This process is used to fill the syringe pump 20. In a subsequent dosing operation, the switching valve 18 is switched over in order to effect a fluid connection of the pumping chamber 26 via the fluid line 10 with the micro-solenoid valve 12.
- a pressure is exerted on the liquid in the pump chamber 26, so that liquid can be dispensed from the metering opening 18 of the tip 14 by rapid switching of the microsolute valve 12 (switching time ⁇ 1 ms).
- Dosing devices of the type shown in Fig. 7 are sold for example by the company Cartesian.
- FIG. 8 An alternative principle, as practiced by, for example, Delo and Vermes, is shown in FIG.
- a pressure vessel 40 is provided in which a pressurized liquid 42 is located.
- An outlet of the pressure vessel 40 is connected via a fluid line 44 to a fast-switching valve 46, which in turn is connected via a fluid line 48 with a nozzle opening, which is shown in Fig. 8 only schematically as an arrow. Also at This arrangement can be discharged by rapidly switching the valve 46 liquid in the free jet from the nozzle opening.
- microdosing devices are described, for example, in DE-A-19802367, DE-A-19802368 and EP-A-0725267.
- the Mikrodosiervoriquesen described therein comprise a pumping chamber to which a flexible membrane is adjacent and which is connected via a feed line to a reservoir and via a discharge line with a nozzle opening.
- An example of such a microdosing device will be explained below with reference to FIGS. 9a-9c.
- FIG. 9 a shows a schematic cross section through such a microdosing device in the idle state.
- the metering device comprises a metering head 50 and an actuating device 52.
- the metering head 50 is formed by two interconnected substrains 54, 56 in which respective recesses are produced.
- the first substrate 54 is structured such that a reservoir connection 58, an inlet channel 60 and a metering chamber 62 are formed therein.
- the lower substrate 56 is structured to have therein a nozzle connection 64, a nozzle 66 having a nozzle channel and an outlet opening, and an outlet portion 68 having a substantially larger cross-section than the outlet opening of the nozzle 66.
- a membrane 70 is further formed therein.
- the actuator 52 has a displacer 72 through which the diaphragm 70 can be deflected downwardly to reduce the volume of the metering chamber 62, as shown in Figure 9b.
- This reduction in the volume of the metering chamber 72 results in a return flow 74 through the inlet channel 60 and the reservoir connection 58.
- a forward flow results through the nozzles ⁇ connection 64 and the nozzle 66, so that there will be a delivery of liquid 76 at the outlet end of the nozzle 66th
- the ratio between reflux 74 and metered liquid 76 depends on the ratio of the flow resistance of the fluid connection between the reservoir and the metering chamber to the flow resistance between the metering chamber and the discharge opening of the nozzle 66.
- the displacer 72 is moved upwards using the actuator 52, see Fig. 9c, so that it finally resumes the original position as shown in Fig. 9a by its elasticity.
- This return of the membrane 70 results in an increase in the volume of the metering chamber 62, so that a re-filling flow 78 takes place from the reservoir through the reservoir connection 58 and the inlet channel 60.
- the recovery of the membrane 70 is slow enough to avoid being overcome by the same capillary forces that hold liquid in the nozzle 66.
- Microdosage devices as described above with respect to Figures 9a-9c were originally developed for enzyme dosage in biochemistry. Using these devices, liquids with viscosities up to 100 mPas in a volume range from 1 nL to 1000 nL can be metered very media-independently and precisely.
- the liquid to be dispensed is metered by displacement from the metering chamber of a metering chip, preferably made of silicon, in the free jet.
- this method requires a comparatively complex microcomponent.
- US Pat. No. 3,683,212 discloses a droplet ejection system in which a tubular piezoelectric transducer has a fluid line with a nozzle plate in which a nozzle orifice plate is provided. formed, connects. A short rise time voltage pulse is applied to the transducer to cause contraction of the transducer. The resulting sudden decrease in trapped volume causes a small amount of fluid to be expelled from the orifice in the orifice plate. The liquid is kept under no or a low static pressure. The surface tension at the opening prevents liquid from flowing out when the transducer is not actuated. The ejected liquid is replaced by a capillary forward flow of liquid in the line.
- the droplet is generated by means of an acoustic principle similar to the piezoelectric ink-jet method.
- an acoustic pressure wave is generated in a rigid fluid conduit, for example a rigid glass capillary, which at the delivery location locally results in a high pressure gradient, which leads to droplet detachment.
- the actuation time of the actuator is here in the order of magnitude of the sound propagation in the system, which is usually a few microseconds. Therefore, in this context, the acoustic impedance of the fluid lines below and above the actuator for the design of importance. It is therefore a pulse method in which a high acoustic impulse is generated at low volume displacement.
- a sound wave is generated with pressure maxima and pressure minima between the location of the actuation and the discharge point, wherein a discharge of liquid is effected by a corresponding pressure at the delivery point.
- the fluid line is only deformed negligibly, only sound is transmitted essentially by the actuator and the elasticity of the fluid line does not play a decisive role.
- a device for metering of liquids which provides a liquid supply having a hose connected at one end to a liquid reservoir and the other end is open.
- the hose rests on a rest base and a hammer is provided on the side of the hose opposite to the restock base.
- the hammer is displaceable in periodic oscillations in the direction transverse to the tube axis, so that the entire tube cross-section is squeezed by the hammer, that is, the flow area is brought to substantially zero.
- impulsive force impulses are exerted on the tube and expelled individual drops of liquid from the open end.
- the present invention provides a microdosing device having the following features:
- a fluid conduit having a flexible hose, preferably a polymer hose, having a first end for connection to a fluid reservoir and a second end at which an outlet port is located; and
- an actuator having an adjustable stroke displacer through which the volume of a portion of the flexible tube is changeable to thereby communicate fluid flow as a free-flying droplet or as a free-flying jet by moving the displacer between a first end position and a second end position the outlet opening, wherein the tube is partially compressed in at least the first end position or the second end position.
- the present invention provides a microdosing device having the following features:
- a fluid conduit having a first end for connection to a fluid reservoir and a second end having an outlet port therein, the fluid conduit having a portion along which a cross-section of the fluid conduit is changeable to effect a change in the volume of the fluid conduit;
- an actuator disposed at a position along the portion of the fluid conduit for effecting a change in the volume of the fluid conduit to thereby dispense liquid as free-flying droplets or free-flowing jet from the outlet port;
- a ratio of a fluidic impedance between the position of the actuator and the outlet port to a fluidic impedance between the fluid reservoir and the position of the actuator is variable by changing the position of the actuator such that a dosing volume delivered to the outlet port is thereby variable by at least 10%
- fluidic impedance is meant the combination of fluidic resistance and fluidic inductance determined by the length and flow area of a conduit.
- the present application thus makes it possible to adjust the metering volume by either adjusting the stroke of the actuating device and / or adjusting the position of the actuating device along a fluid line whose volume can be changed.
- a variability of the ratio of the mentioned flow resistances can preferably be achieved by forming the fluid line between the liquid reservoir and the ejection opening with a substantially linear structure, ie having a cross section without sudden cross-sectional changes between the liquid reservoir and the ejection opening. In the simplest case, this can be achieved by the fluid line between the liquid reservoir and the discharge opening having a substantially constant cross section in the quiescent state.
- the present invention requires no fine mechanical or microstructured components, as they are necessary with other drop generators, whereby the manufacturing cost can be significantly reduced and the reliability is increased. Further, the fluid-carrying parts can be made as disposable components simply made of plastic, such as polyimide, thereby eliminating a costly cleaning when changing media.
- the present invention further provides a method for the metered dispensing of liquids, comprising the following steps:
- the present invention also provides methods for setting a desired metering volume in a metering process using a microdosing device according to the invention, comprising the following step:
- the present invention further provides a method for setting a desired metering volume in a container siervorgang using a microdosing device according to the invention, comprising the following step:
- the present invention thus provides additional degrees of freedom in setting a desired metering volume.
- a desired metering volume can be set by the above-mentioned steps. If the stroke and thus the displacement of the actuating device can be adjusted, a desired dosing volume range can be set by the above-mentioned steps, in which case the respective dosing volume lying in the desired dosing volume range can be set by adjusting the stroke or the displacement of the actuating device.
- a characteristic feature and a significant advantage of volume displacement systems, as realized by the present invention, is that in the same dosing volume is largely independent of the viscosity of the liquid to be dispensed.
- the actuating device may be designed together with the fluid line in order to allow a complete squeezing of the fluid line through the displacer as an extreme case of the volume displacement.
- a valve function can additionally be implemented.
- the possibility of a complete interruption of the fluid line between reservoir and discharge point can thus represent a further advantage over known methods.
- a continuous pressure gradient is established over the entire fluid line, with the fluid being pushed out of the line, starting from the displacer. The entire fluid located between the displacer and the outlet opening is moved in the direction of the outlet opening. Acoustic phenomena are irrelevant here, since the volume displacement takes place on a time scale of a few milliseconds (much slower than with pulse methods).
- FIGS. 2a-2d are schematic views of an embodiment of a microdosing device according to the invention.
- FIG. 3 schematically shows an image sequence of the droplet formation
- Fig. 4 is a diagram showing drop volumes generated by a prototype
- 5a and 5b show schematic illustrations for illustrating how a dosing volume range can be set in a microdosing device according to the invention
- FIGS. 7-9 are schematic illustrations of known microdosing systems.
- 10a and 10b are schematic representations of alternative embodiments of microdosing devices according to the invention.
- FIGS. 1 a to 1 c With reference to the schematic representations in FIGS. 1 a to 1 c, the essential features of the present invention and the concept underlying the same are explained below.
- the present invention relates to a device or a method for producing microdrops or microarrays, especially in the nanoliter to picoliter range.
- the central element of a microdosing device according to the invention is a fluid-carrying line whose Einlassöff ⁇ voltage is connected to a liquid reservoir in which is the medium to be metered. At the other end of the line is an outlet opening through which the liquid to be dispensed can be dispensed.
- the fluid-carrying line is preferably made primarily of an elastic material, so that the volume of the conduit between inlet opening and outlet opening can be varied by deformation of the conduit, for example by compressing it.
- FIGS. 1 a to 1 c The essential elements of a metering device according to the invention during various phases of a metering process are shown in FIGS. 1 a to 1 c.
- a fluid conduit 100 which in preferred embodiments of the present invention is an elastic polymer tube, includes an inlet end 102 for connection to a fluid reservoir and an outlet end 104, can be delivered to the microdrop or micro-beams.
- the outlet end 104 can also be referred to as a nozzle.
- Respective walls 106 of the elastic poly erschlauchs 100 are shown in FIGS. La to lc by dashed lines.
- An actuator 108 in the form of a displacer which has a connection part 110 to which the displacer 108 can be attached to an actuator for driving the displacer 108.
- the elastic polymer tube has a substantially constant cross-section from its inlet end 102 to its outlet end 104, which will generally be circular.
- a region 112 disposed below the displacer 108 may be referred to as a dosing chamber region defined by the position of the displacer 108 with respect to the elastic polymer tube 100.
- a portion 114 that begins substantially at the right end of the displacer 108 represents an exhaust passage that fluidly connects the displacer portion 112 to the outlet end 104.
- the displacer 108 may include a displacer surface 120 extending at an angle to the wall 106 of the polymer tube 100, which, during operation of the microdosage device, permits the generation of a preferential direction of liquid flow towards the outlet opening 104 by an axially asymmetric volume change.
- the fluid line 100 is filled either by itself via an externally generated pressure difference or by capillary forces.
- An externally generated pressure difference may be applied, for example, by using a liquid reservoir by pressurizing the liquid.
- a negative pressure (negative pressure) relative to the outlet end may be applied to prevent leakage of liquid from the outlet end in the non-actuated state if the capillary forces are too weak for this. This counteracting pressure must be overcome when filling by the capillary forces.
- a first phase which may be termed a metering phase
- liquid is displaced from the conduit by a reduction in the line volume between the inlet port and the outlet port. This is achieved by placing the displacer 108 down, i. H. is moved toward the polymer tube 100, so that a compression of the polymer tube takes place in the displacement 112. This downward movement is illustrated by arrows 122 in FIG.
- the displacer region 112 thus represents the active region of the micro-metering device according to the invention.
- the fluid displaced from the conduit due to this change in volume of the fluid conduit 100 becomes the ends the line out or stored by a change in the line cross-section elsewhere, if the line has a fluidic capacity.
- the fluidic resistances between outlet opening 104 and active area 112, in which the volume change occurs ie the fluidic impedance of outlet channel 114
- the fluidic impedance of the line section between active area 14 and inlet opening 112 ie, the fluidic impedance of inlet channel 116)
- Good dosing quality can be achieved, for example, if the volume change in the vicinity of the outlet opening 104 is performed with a high dynamic range (for example 50 nL within one millisecond).
- the fluidic impedance of the outlet channel 114 may be made small compared to the fluidic impedance of the inlet channel 116, so that a large part of the displaced liquid is expelled from the outlet opening 104.
- the displacer is arranged in the vicinity of the outlet opening 104 if the length of the inlet channel 116 is at least twice the length of the outlet channel 114, more preferably at least five times as large and even more preferably at least ten times is great.
- the volume between inlet opening 102 and outlet opening 104 is increased again in a second phase, which can be referred to as a refill phase.
- a second phase which can be referred to as a refill phase.
- This is achieved by moving the displacer 108 away from the fluid conduit 100 in the direction of an arrow 132, as shown in FIG. 1c. Due to this change in volume, liquid from the reservoir flows through the inlet port 102 and the inlet channel 116 into the conduit, and more particularly into the active area 112 thereof, as indicated by an arrow 134 in FIG.
- the suction of air through the outlet opening 104 is prevented at correspondingly small line cross-sections by capillary forces.
- a preferred direction for filling from the reservoir can be predetermined by a hydrostatic pressure difference between inlet opening and outlet opening.
- the liquid reservoir could be subjected to a pressure.
- FIGS. 2a to 2d show a drop generator using a microdosing device according to the invention with corresponding holders for the fluid line or the actuating device.
- Fig. 2a shows a side view of the drop generator
- Fig. 2b is a bottom view thereof.
- Fig. 2c is a sectional view taken along the line A-A of Fig. 2b
- Fig. 2d shows an enlargement of the section B in the scale 5: 1.
- the drop generator shown in FIGS. 2a to 2d comprises a polyimide tube 150, which may for example have an inner diameter of 200 .mu.m.
- a bearing block 152 and an abutment block 154 are provided for storage of the polyimide tube 150.
- a guide groove is provided in the bearing block 152 and / or the abutment block 154, in which the polyimide hose is inserted, so that the polyimide hose between bearing block and abutment block is securely mounted in a stabilized manner.
- the bearing block 152 and the abutment block 154 are attached to a holding portion 160 of a holder 162 using, for example, retaining screws 156.
- the holder 162 is further formed to hold on the opposite side of the abutment 154 of the polyimide tube 150 a displacer 164, with the aid of the tube in the active region thereof can be compressed, whereby the volume change of the invention between the inlet opening and outlet opening is achieved.
- the displacer is thereby driven by a piezo stack actuator (not shown), the deflection of which can be electronically controlled, and which is connected via an adapter 166 to the displacer 164.
- the displacer 164 again has a relative beveled to the polyimide hose, that is, at an angle, displacement surface.
- the holder 162 further comprises a receptacle 170 for the drive unit in the form of Piezostackackaktuators. Furthermore, the holder 162 may have a recess 172 penetrating the same in order to enable it to be attached to a device which also contains the drive unit, for example by using a screw connection.
- FIG. 3 shows different phases of a metering operation carried out by means of the prototype, in each case the polyimide hose 150 with its outlet end 180 being shown.
- FIG. 4 shows the delivered mass in micrograms at a number of 1800 dosing processes using the prototype, wherein water was used as the liquid to be dosed.
- the average drop mass was 22.57 ⁇ g, with a standard deviation ⁇ of 0.35 ⁇ g.
- the polyimide tube had a diameter of 200 ⁇ m.
- the gravimetric measurement of the reproducibility shown in FIG. 4 proves that with the concept according to the invention a precision can be achieved which at least corresponds to that of conventional metering devices and is even superior to it.
- a desired metering volume or a desired metering volume range can be set in a microdosing device according to the invention.
- FIGS. 5a and 5b Shown schematically in FIGS. 5a and 5b is the polymer tube 100, whose inlet opening 102 is fluidically connected to a liquid reservoir 200, and whose outlet end 104 constitutes an ejection opening.
- the active area 112 as well as the outlet channel 114 and the inlet channel 116 are defined by the position of the displacer 108.
- the inlet channel 116 and the outlet channel 114 have substantially equal lengths x x and x 2 , so that their fluidic impedance is substantially identical assuming a constant cross section of the tube 100.
- volume displacement caused by the displacer 108' would result in flows of equal size flowing toward the outlet port 104 and the inlet port 102.
- the volume expelled through the outlet port 104 would be half the volumetric displacement caused by the displacer 108 '.
- the displacer 108 ' is arranged in the vicinity of the outlet opening 104.
- the length Xi of the intake passage 116 is about five times as large as the length of the exhaust passage x 2 .
- the fluidic impedance of the inlet channel 116 at constant cross-section of the tube 100 is five times that of the outlet channel 114, so that a much greater proportion of the volume change effected by the displacer 108 'will flow toward the outlet port 104 and thus expel through it causes.
- the above adjustment of the position may be adjustment a desired dosing volume range while the final Position of the desired metering volume is carried out in the set Dosiervolumen Scheme by a corresponding control of the displacer.
- the dosing volume delivered at the outlet opening can be adjusted by changing the position of the displacer, as long as the ratio of the flow resistances of the inlet channel and outlet channel can be changed appreciably by changing the position of the displacer.
- An appreciable change is to be understood here which results in a change of a dispensing volume dispensed at the outlet opening by at least 10%, the actual setting range being dependent on the range over which the position of the displacer can be adjusted. It can be realized by changing the position of the displacer using the microdosing devices according to the invention also changes the dispensed dosing volume by 50% and above.
- This adjustability according to the invention of the ratio of the flow resistances of the inlet channel and the outlet channel is preferably possible according to the invention in that between metering chamber, i. H. active region, and inlet channel or outlet channel no sudden cross-sectional changes take place.
- the cross-section of the fluid conduit is from the segment of the displacement, i. H. the active area, to the outlet opening at rest constant.
- the entire fluid line between the liquid reservoir and the outlet has a substantially constant cross-section.
- FIGS. 6a and 6b A second possibility, as according to the invention a desired metering volume or a desired metering volume range can be adjusted, can be seen in FIGS. 6a and 6b.
- the displacer 108 ' has a length li along the tube 100
- a displacer 208 has a length 1 2 along the tube 100. has.
- the length 1 2 is greater than the length li, so that the displacer 208 allows a greater volume increase of the fluid line 100 with the same stroke.
- a desired metering volume or, similar to the above explanations a desired metering volume range can be set.
- the present invention thus provides a microdosing device which has a fluid line filled with a medium to be metered, one end of which is connectable to a fluid reservoir and at the other end of which there is an outlet opening, and an actuating device, through which the volume of a particular segment the fluid line can be changed over time, so that is given by the volume change liquid as free-floating droplets or as free-flying beam at the Auslasso réelle.
- the entire fluid line can be formed by a flexible polymer tube.
- only the particular segment addressed can be formed by a flexible polymer tube, while the supply and discharge of this segment are formed by a rigid fluid line.
- the fluid line of a microdosing device can also be formed by a channel formed in a substantially rigid carrier and covered by a membrane.
- the channel without sudden cross-sectional changes and preferably formed with a constant cross-section in the carrier, so that even in this embodiment, the fluid resistance of the inlet channel and Au ⁇ lasskanal can be adjusted by appropriate positioning of the Verdrangers, thus changing the dispensed at the Auslasso réelle dispensing volume to reach at least 10%.
- the Ver ⁇ crowding instead to an elastic segment of the fluid line.
- the elastic segment in the Flu ⁇ can idön, for example, the flexible polymer tube or membrane, taking again after actuation by itself the initial state, so that the displacer is not fixedly connected to the fluid conduit connected must be such that the fluid conduit as a single disposable component can be executed.
- the present invention also includes drop generators in which a plurality of microdosing devices according to the invention are arranged in parallel. Such parallel arranged microdosing can be controlled separately to dose different liquids or the same liquids.
- a drop generator may have a plurality of fluid lines, which are simultaneously driven by a displacer, so that the same or different liquids can be metered by the same.
- the inlet ends of the different fluid lines may be connected to the same or different liquid reservoirs.
- a microdosing device can thus consist of one or more microdroplet generators each having an (elastic) fluidic line filled with a medium to be dosed, one end of which has an inlet opening connected to a fluid reservoir and at the other end thereof an outlet opening, wherein there may be a pressure difference between the inlet opening and the outlet opening, and an actuating device, by means of which the volume of the line between the liquid reservoir and outlet opening can be changed over time, wherein in a first phase the fluid volume between the inlet opening and outlet opening starts at a sufficient speed from its initial one Volume is reduced to a smaller volume, thereby reducing a microdrop is ejected through the outlet port and a portion of the displaced volume is allowed to escape to the inlet port, the volume of the microdrop plus the volume receding into the reservoir through the inlet port substantially corresponding to the volume change effected by the actuator corresponds, and a second phase, in which the volume between the inlet opening and outlet opening is increased again, whereby the fluidic line driven
- an automated holder can also be provided, which enables an automatic adjustment of the position of the displacer to the fluid line, for example in response to a signal indicating a desired metering volume range or a desired metering volume.
- individual free-floating microdroplets are preferably created at an outlet port in contact with the surrounding atmosphere to thereby deliver fluid as free-flying droplets or free-flowing jet at the outlet port.
- the present invention enables the ejection of a droplet already in a single actuation cycle of the actuator, during which the displacer once causes a reduction in the volume of the fluid line, thereby expelling the droplet.
- the present invention allows adjustment of the dosing volume by adjusting the stroke of the movement means and / or arranging the actuator at a predetermined position along the portion of a fluid conduit.
- a displacer with a matched axial length can be selected.
- the drop volume is determined by the extent of the hammer along the tube axis and the hose diameter.
- the entire volume located in the relevant tube section is displaced.
- the displaced volume which then - with constant other arrangement - determines the drop volume substantially:
- V is the displaced volume
- a is the length of the displacer
- d is the diameter of the tube.
- the present invention enables a variable adjustment of the dosing volume without having to connect a hose with a different diameter or a displacer with different dimensions.
- the present invention also enables dosing with non-periodic excitation. This is advantageous, inter alia, when targeted non-periodic patterns are to be printed on a substrate.
- the actuating device is in each case designed to effect an actuation of the hose, starting from an uncompressed state thereof.
- the hose in standby mode is partially or completely squeezed, i. is compressed.
- a schematic cross-sectional view of such an embodiment is shown in FIG. 10a.
- the hose 100 rests with its back against a counter-holding element 300.
- a piezoactuator 302 is attached to a holder 304 of an actuator.
- a displacer 306 is arranged at the front end of the piezoelectric actuator 302, a displacer 306 is arranged.
- the tube 100 is completely squeezed off in standby mode.
- the metering cycle starts with a slow retraction of the piezoactuator 302, so that the cross section of the hose 100 is partially released.
- liquid from the reservoir to which the tube 100 is connected at the end 102 opposite the outlet opening 104 flows into the previously squeezed area around which compensate for increasing tube volume.
- the actual dosing process with the droplet formation at the outlet end 104 then takes place with the rapid extension of the piezoactuator 302 in order to reduce the tube volume again.
- the metered volume is, as in the embodiments described above, defined by the actuating path of the piezoelectric actuator 302 and can thus be controlled by varying the operating voltage or by varying the charging or discharging current in the piezoactuator 302.
- An advantage of the configuration shown in FIG. 10a is that the clamped hose has a significantly lower rate of evaporation of the medium to be metered than the hose which is normally open.
- the embodiment thus includes an integrated locking mechanism.
- the extended state of the piezo actuator is the state in which the electrical voltage is applied.
- the embodiment of an integrated shutter mechanism shown in FIG. 10a entails continuous, albeit small, energy consumption.
- An integrated shutter mechanism with reduced power consumption is implementable by providing the actuator with biasing means, such as a spring, which presses the displacer against the polymer tubing to achieve partial or total hose pinch off in standby mode.
- the actuating device then preferably has an actuator, which is arranged in order to control the displacement. ger against the force of the biasing device to move and release the tube cross section partially or completely.
- FIG. 10b An exemplary embodiment of such an integrated closure mechanism is shown in FIG. 10b.
- the hose 100 in turn abuts against a counter-holding device 310.
- An actuator in this embodiment includes a combination of a spring 312 and a piezo stack actuator 314.
- the actuator further includes a displacer 316 that is rigidly coupled to an actuator plate 318.
- two coupling rods 320 and 322 are shown in FIG. 10b.
- the spring 312 abuts a counter-holding element 324 at its right-hand end and, in the non-actuated state of the actuator 314, presses the displacer 316 against the hose 100 in order to squeeze it.
- This embodiment makes it possible to realize a metering device whose hose is squeezed when the electrical supply voltage is switched off, so that it has an integrated shutter mechanism without continuous energy consumption.
- the displacer 316 is pressed onto the tube 100 by the spring so that it is pressed against the counter-support 310 and squeezed off. If a dosing operation is to take place, the piezoactuator 314 is extended by applying an electrical voltage and thus the displacer 316 is reset against the spring force. The tube relaxes and the liquid to be dispensed flows from the reservoir which is connected to the side 102 of the tube opposite the outlet opening 104. Rapid retraction of the piezo stack actuator 318 causes the tube 100 to be squeezed again via the spring 312, which is dimensioned sufficiently strongly for this purpose.
- the spring is rigid enough dimensioned so that liquid is metered out as a free-flowing jet from the discharge opening 104.
- the dosed volume is in turn defined by the travel of the piezoelectric actuator and can thus be controlled by varying the operating voltage or via the variation of the charging or discharging current at the piezoelectric tape actuator.
- the displacer is moved between a first end position and a second end position, wherein the polymer tube is partially compressed in the first end position or the second end position is.
- the first end position defines a larger tube volume than the second end position, so that liquid is metered out of the ejection end by moving the displacer from the first end position into the second end position.
- the first end position can then define a completely relaxed state of the hose or a partially compressed state of the same.
- the second end position may include a partially compressed state or a fully compressed state of the polymer tube.
- the hose wall is moved by the actuating device or the displacer over part of the clear cross section of the flexible polymer tube.
- the tube wall is moved over the entire clear cross-section of the tube.
- the exemplary embodiments shown in FIGS. 10a and 10b can also be implemented in such a way that the position of the actuating device can be varied in order thereby to be able to vary the dosing volume dispensed from the outlet opening.
Landscapes
- Health & Medical Sciences (AREA)
- Clinical Laboratory Science (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
- Measuring Volume Flow (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10337484A DE10337484B4 (de) | 2003-08-14 | 2003-08-14 | Mikrodosiervorrichtung und Verfahren zur dosierten Abgabe von Flüssigkeiten |
| PCT/EP2004/009063 WO2005016534A1 (fr) | 2003-08-14 | 2004-08-12 | Dispositif de microdosage et procede de delivrance dosee de liquides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP1654068A1 true EP1654068A1 (fr) | 2006-05-10 |
| EP1654068B1 EP1654068B1 (fr) | 2007-01-24 |
Family
ID=34177580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP04764062A Expired - Lifetime EP1654068B1 (fr) | 2003-08-14 | 2004-08-12 | Dispositif de microdosage et procede de delivrance dosee de liquides |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7900850B2 (fr) |
| EP (1) | EP1654068B1 (fr) |
| JP (1) | JP2007502399A (fr) |
| CN (1) | CN100428998C (fr) |
| AT (1) | ATE352374T1 (fr) |
| DE (2) | DE10337484B4 (fr) |
| WO (1) | WO2005016534A1 (fr) |
Families Citing this family (89)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0607427D0 (en) * | 2006-04-13 | 2006-05-24 | Imi Vision Ltd | Fluid dispenser |
| DE102006047579A1 (de) * | 2006-10-05 | 2008-04-17 | Institut Für Solarenergieforschung Gmbh | Verfahren zur Herstellung von Solarzellen mit durch eine Ätzlösung lokal strukturierten Oberflächen |
| ITVR20070024A1 (it) * | 2007-02-15 | 2008-08-16 | Z G Camini Inox S R L | Dispositivo di pompaggio particolarmente per fluidi contenenti sospensioni solide |
| US9394153B2 (en) | 2007-03-15 | 2016-07-19 | The Coca-Cola Company | Multiple stream filling system |
| US8479784B2 (en) * | 2007-03-15 | 2013-07-09 | The Coca-Cola Company | Multiple stream filling system |
| US8387599B2 (en) | 2008-01-07 | 2013-03-05 | Mcalister Technologies, Llc | Methods and systems for reducing the formation of oxides of nitrogen during combustion in engines |
| WO2011025512A1 (fr) | 2009-08-27 | 2011-03-03 | Mcallister Technologies, Llc | Injecteurs et allumeurs de combustible intégrés et procédés d'utilisation et de fabrication associés |
| US7628137B1 (en) * | 2008-01-07 | 2009-12-08 | Mcalister Roy E | Multifuel storage, metering and ignition system |
| US8986253B2 (en) | 2008-01-25 | 2015-03-24 | Tandem Diabetes Care, Inc. | Two chamber pumps and related methods |
| EP2252542B1 (fr) | 2008-02-04 | 2015-09-30 | The Coca-Cola Company | Procédés de création de produits de boisson personnalisés |
| DE102008032328A1 (de) | 2008-07-09 | 2010-01-14 | Schaeffler Kg | Wälzlager mit einem Schmierungssystem |
| CA2753214C (fr) * | 2009-02-27 | 2017-07-25 | Tandem Diabetes Care, Inc. | Procedes et dispositifs pour la determination d'un volume de reservoir d'ecoulement |
| US9250106B2 (en) | 2009-02-27 | 2016-02-02 | Tandem Diabetes Care, Inc. | Methods and devices for determination of flow reservoir volume |
| DE102009014647B4 (de) * | 2009-03-26 | 2013-03-28 | Helmholtz-Zentrum Für Umweltforschung Gmbh - Ufz | Dosiervorrichtung für Bioreaktoren |
| CA2921304C (fr) | 2009-07-30 | 2018-06-05 | Tandem Diabetes Care, Inc. | Dispositif de pompe a infusion dote d'une cartouche jetable a aeration de pression et retroaction de pression |
| US9109423B2 (en) * | 2009-08-18 | 2015-08-18 | Halliburton Energy Services, Inc. | Apparatus for autonomous downhole fluid selection with pathway dependent resistance system |
| WO2011071607A2 (fr) | 2009-12-07 | 2011-06-16 | Mcalister Roy E | Allumeurs d'injecteur de carburant intégrés pour applications moteur importantes et procédés associés d'utilisation et de fabrication |
| US8757511B2 (en) | 2010-01-11 | 2014-06-24 | AdvanJet | Viscous non-contact jetting method and apparatus |
| US8205805B2 (en) | 2010-02-13 | 2012-06-26 | Mcalister Technologies, Llc | Fuel injector assemblies having acoustical force modifiers and associated methods of use and manufacture |
| EP2392842B1 (fr) | 2010-06-02 | 2013-05-08 | Technische Universität Berlin | Dispositif de soupape pour la commande de l'écoulement d'un fluide à travers un canal de fluide, agencement et dispositif de soupape à voies multiples |
| DE102010017216A1 (de) | 2010-06-02 | 2011-12-08 | Technische Universität Berlin | Ventilvorrichtung zum Steuern eines Flusses eines Fluides durch einen Fluidkanal, Anordnung sowie Mehrwegventilvorrichtung |
| US20130153738A1 (en) * | 2010-07-02 | 2013-06-20 | Mark J. Meiners | Anti-spin mounting pole and method of forming |
| USD673536S1 (en) * | 2010-07-02 | 2013-01-01 | Tubular USA, Inc. | Satellite mounting pole |
| US10154923B2 (en) | 2010-07-15 | 2018-12-18 | Eyenovia, Inc. | Drop generating device |
| FR2963872B1 (fr) * | 2010-08-18 | 2012-08-03 | Exel Ind | Dispositif et procede pour distribuer un produit liquide a projeter sur une surface |
| CN103429348B (zh) | 2011-01-21 | 2016-03-09 | 拜奥-多特公司 | 具有纵向变换器和可替换毛细管的压电分配器 |
| US8919377B2 (en) | 2011-08-12 | 2014-12-30 | Mcalister Technologies, Llc | Acoustically actuated flow valve assembly including a plurality of reed valves |
| US9346075B2 (en) | 2011-08-26 | 2016-05-24 | Nordson Corporation | Modular jetting devices |
| US9254642B2 (en) | 2012-01-19 | 2016-02-09 | AdvanJet | Control method and apparatus for dispensing high-quality drops of high-viscosity material |
| EP2662137A1 (fr) | 2012-05-08 | 2013-11-13 | Roche Diagniostics GmbH | Ensemble de distribution |
| EP2662138A1 (fr) | 2012-05-08 | 2013-11-13 | Roche Diagniostics GmbH | Distributeur de microfluidique, cartouche et système d'analyse pour analyser un échantillon biologique |
| US9180242B2 (en) | 2012-05-17 | 2015-11-10 | Tandem Diabetes Care, Inc. | Methods and devices for multiple fluid transfer |
| DE102012209314B4 (de) | 2012-06-01 | 2015-04-02 | Albert-Ludwigs-Universität Freiburg | Vorrichtung und Verfahren zur Abgabe oder Aufnahme eines Flüssigkeitsvolumens |
| US9555186B2 (en) | 2012-06-05 | 2017-01-31 | Tandem Diabetes Care, Inc. | Infusion pump system with disposable cartridge having pressure venting and pressure feedback |
| GB201217390D0 (en) * | 2012-09-28 | 2012-11-14 | Agplus Diagnostics Ltd | Test device and sample carrier |
| US9169821B2 (en) | 2012-11-02 | 2015-10-27 | Mcalister Technologies, Llc | Fuel injection systems with enhanced corona burst |
| US9169814B2 (en) | 2012-11-02 | 2015-10-27 | Mcalister Technologies, Llc | Systems, methods, and devices with enhanced lorentz thrust |
| US8752524B2 (en) | 2012-11-02 | 2014-06-17 | Mcalister Technologies, Llc | Fuel injection systems with enhanced thrust |
| US9527075B2 (en) | 2012-11-05 | 2016-12-27 | Austen Bioinnovation Institute In Akron | Low-volume syringe pipette |
| US9200561B2 (en) | 2012-11-12 | 2015-12-01 | Mcalister Technologies, Llc | Chemical fuel conditioning and activation |
| US9194337B2 (en) | 2013-03-14 | 2015-11-24 | Advanced Green Innovations, LLC | High pressure direct injected gaseous fuel system and retrofit kit incorporating the same |
| US9173998B2 (en) | 2013-03-14 | 2015-11-03 | Tandem Diabetes Care, Inc. | System and method for detecting occlusions in an infusion pump |
| DE202013003390U1 (de) | 2013-04-11 | 2014-07-14 | Brand Gmbh + Co Kg | Pipettiervorrichtung mit einer Mikrodosiereinheit |
| DE102013006227A1 (de) | 2013-04-11 | 2014-10-16 | Brand Gmbh + Co Kg | Pipettiervorrichtung mit einer Mikrodosiereinheit |
| EP3030352B1 (fr) | 2013-08-07 | 2019-03-20 | Roche Diagnostics GmbH | Cartouche pour distribuer un fluide, analyseur automatique et procédé d'analyse d'un échantillon biologique |
| WO2015120053A1 (fr) | 2014-02-04 | 2015-08-13 | Austen Bioinnovation Institute In Akron | Piston pour pipette seringue à faible volume |
| JP5802347B1 (ja) * | 2014-05-20 | 2015-10-28 | エンジニアリングシステム株式会社 | 微量液体滴下方法および微量液体ディスペンサ |
| US10221060B2 (en) | 2014-05-20 | 2019-03-05 | Engineering System Co., Ltd. | Microvolume-liquid dispensing method and microvolume-liquid dispenser |
| US10928236B2 (en) * | 2014-07-25 | 2021-02-23 | Hoffmann-La Roche Inc. | Dosing a fluid at a volume of less than one milliliter |
| DE102015009695A1 (de) | 2014-08-07 | 2016-02-11 | Brand Gmbh + Co Kg | Pipettiervorrichtung mit einer Mikrodosiereinheit |
| DE202014006241U1 (de) | 2014-08-07 | 2015-11-12 | Brand Gmbh + Co Kg | Pipettiervorrichtung mit einer Mikrodosiereinheit |
| DK3204520T3 (da) * | 2014-10-08 | 2020-04-20 | Univ Cornell | Fremgangsmåde til identificering og kvantificering af nukleinsyreekspression, splejsningsvariant, translokation, kopiantal eller methyleringsændringer |
| EP3244851B1 (fr) * | 2015-01-12 | 2024-10-16 | Bausch + Lomb Ireland Limited | Dispositif de distribution de micro-gouttelettes |
| JP6185510B2 (ja) * | 2015-03-24 | 2017-08-23 | エンジニアリングシステム株式会社 | 微量液体ディスペンサ |
| KR20170135862A (ko) | 2015-04-10 | 2017-12-08 | 켄달리온 테라퓨틱스 인코포레이티드 | 교체 가능한 앰플을 갖는 압전 디스펜서 |
| US10492141B2 (en) | 2015-11-17 | 2019-11-26 | Tandem Diabetes Care, Inc. | Methods for reduction of battery usage in ambulatory infusion pumps |
| WO2017085624A1 (fr) * | 2015-11-20 | 2017-05-26 | Advanced Microfluidics Sa | Micropompe |
| DE202016004140U1 (de) | 2016-07-05 | 2017-10-08 | Brand Gmbh + Co Kg | Pipettiervorrichtung zum Aspirieren und Dispensieren von Flüssigkeiten |
| KR102412086B1 (ko) | 2017-01-20 | 2022-06-22 | 켄달리온 테라퓨틱스 인코포레이티드 | 압전 유체 분배기 |
| CN107101689A (zh) * | 2017-05-18 | 2017-08-29 | 长沙执先智量科技股份有限公司 | 一种直压式流体计量方法及计量装置 |
| CN115300226A (zh) | 2017-06-10 | 2022-11-08 | 艾诺维亚股份有限公司 | 用于将一体积的流体输送到眼睛的设备 |
| EP3450020B1 (fr) | 2017-09-01 | 2021-04-07 | Eppendorf AG | Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide |
| EP3485974B2 (fr) | 2017-11-17 | 2024-07-10 | Eppendorf SE | Dispositif de microdosage permettant le dosage de plus petits échantillons de fluide |
| CN111712219A (zh) | 2017-12-08 | 2020-09-25 | 科达莱昂治疗公司 | 流体递送对准系统 |
| US11529458B2 (en) | 2017-12-08 | 2022-12-20 | Amf Medical Sa | Drug delivery device |
| KR101914166B1 (ko) * | 2018-04-03 | 2018-11-01 | 주식회사 팀즈 | 정밀토출 제어 디스펜서 |
| US12350194B1 (en) | 2018-04-12 | 2025-07-08 | Bausch + Lomb Ireland Limited | Topical ocular delivery of fluids with controlled mass dosing and wireless communication |
| US20190314198A1 (en) | 2018-04-12 | 2019-10-17 | Kedalion Therapeutics, Inc. | Topical Ocular Delivery Methods and Devices for Use in the Same |
| EP3817696B8 (fr) | 2018-07-03 | 2024-12-11 | Bausch + Lomb Ireland Limited | Dispositifs d'administration oculaire topique |
| DE102018131088A1 (de) | 2018-12-05 | 2020-06-10 | Biofluidix Gmbh | Flüssigkeitsdosiervorrichtung zur ballistischen Abgabe von Dosiermengen im Nanoliterbereich, Flüssigkeitsdosierverfahren und Pipettierspitze hierfür |
| FR3092011B1 (fr) * | 2019-01-25 | 2021-11-05 | Fluigent | Dispositif et procédé pour créer une émulsion |
| US12097145B2 (en) | 2019-03-06 | 2024-09-24 | Bausch + Lomb Ireland Limited | Vented multi-dose ocular fluid delivery system |
| US11679028B2 (en) | 2019-03-06 | 2023-06-20 | Novartis Ag | Multi-dose ocular fluid delivery system |
| DE102019109493A1 (de) * | 2019-04-10 | 2020-10-15 | Sartorius Stedim Biotech Gmbh | Mindermengen-Flüssigkeitsbehälter |
| DE102019113679A1 (de) | 2019-05-22 | 2020-11-26 | Hamilton Storage Gmbh | Flüssigkeit-Screeningbaugruppe mit mechanischer Auslösung kleinster Flüssigkeitsmengen |
| CN115038414A (zh) | 2019-12-11 | 2022-09-09 | 艾诺维亚股份有限公司 | 用于向眼睛输送流体的系统和装置及使用方法 |
| WO2021151973A1 (fr) * | 2020-01-28 | 2021-08-05 | Mycronic AB | Dispositifs d'éjection dotés d'un actionneur de conduit d'alimentation |
| WO2021212038A1 (fr) | 2020-04-17 | 2021-10-21 | Kedalion Therapeutics, Inc. | Système de distribution sans conservateur à actionnement hydrodynamique comprenant un réservoir de liquide pliable |
| US12290472B2 (en) | 2020-04-17 | 2025-05-06 | Bausch + Lomb Ireland Limited | Hydrodynamically actuated preservative free dispensing system |
| US11925577B2 (en) | 2020-04-17 | 2024-03-12 | Bausch + Lomb Ireland Limted | Hydrodynamically actuated preservative free dispensing system |
| US11938057B2 (en) | 2020-04-17 | 2024-03-26 | Bausch + Lomb Ireland Limited | Hydrodynamically actuated preservative free dispensing system |
| US11241530B1 (en) | 2020-11-23 | 2022-02-08 | Amf Medical Sa | Insulin patch pump having photoplethysmography module |
| US11529464B1 (en) | 2021-06-01 | 2022-12-20 | Amf Medical Sa | Systems and methods for monitoring delivery of microdoses of medication |
| US11857757B2 (en) | 2021-06-01 | 2024-01-02 | Tandem Diabetes Care Switzerland Sàrl | Systems and methods for delivering microdoses of medication |
| US11679199B2 (en) | 2021-06-01 | 2023-06-20 | Amf Medical Sa | Systems and methods for delivering microdoses of medication |
| CN113501925B (zh) * | 2021-07-28 | 2022-11-25 | 中山市长盈包装材料有限公司 | 一种可自发沉水的聚氨酯泡沫塑料及其制备方法和应用 |
| CN114225988B (zh) * | 2021-11-30 | 2023-04-28 | 广东省科学院健康医学研究所 | 一种双向构型微流控液滴生成装置及其制备方法 |
| CN114534630B (zh) * | 2022-01-11 | 2022-12-20 | 深圳本草雾华医药科技有限公司 | 一种细粉及组织液雾化对喷的喷射装置 |
| DE102022211313A1 (de) | 2022-10-25 | 2024-04-25 | Biofluidix Gmbh | Dosiermodul mit Betätigungsfenster |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3171360A (en) * | 1962-03-09 | 1965-03-02 | Walton William Melin | Pulsation type pumps |
| US3683212A (en) * | 1970-09-09 | 1972-08-08 | Clevite Corp | Pulsed droplet ejecting system |
| US4015914A (en) * | 1972-05-18 | 1977-04-05 | Delta Scientific Corporation | Metering pump wherein tubular pump is responsive to force impulses |
| GB1470515A (en) * | 1973-03-30 | 1977-04-14 | Flow Labor Ltd | Micro pipetting apparatus |
| FI70473C (fi) * | 1978-06-23 | 1986-09-19 | Inst Biologicheskoi Fiz | Peristaltisk doserare och medelst denna foerverkligat doseringssystem |
| AU2519184A (en) * | 1983-03-21 | 1984-09-27 | Miles Laboratories Inc. | Microdroplet dispensing apparatus |
| JPS60189834U (ja) | 1984-05-26 | 1985-12-16 | 株式会社島津製作所 | 定量分注装置 |
| DE4314343C2 (de) * | 1993-04-30 | 1995-03-16 | Vermes Technik Gmbh & Co Kg | Vorrichtung zur Dosierung von Flüssigkeiten |
| US5593290A (en) * | 1994-12-22 | 1997-01-14 | Eastman Kodak Company | Micro dispensing positive displacement pump |
| EP0725267B1 (fr) * | 1995-02-01 | 1998-11-18 | Forschungszentrum Rossendorf e.V. | Micro-pipette actionnée électriquement |
| DE19511198A1 (de) * | 1995-03-27 | 1996-10-02 | Bosch Gmbh Robert | Verfahren zur Herstellung von Strukturen, insbesondere für ein Mikrodosiersystem |
| DE19802367C1 (de) * | 1997-02-19 | 1999-09-23 | Hahn Schickard Ges | Mikrodosiervorrichtungsarray und Verfahren zum Betreiben desselben |
| DE19802368C1 (de) * | 1998-01-22 | 1999-08-05 | Hahn Schickard Ges | Mikrodosiervorrichtung |
-
2003
- 2003-08-14 DE DE10337484A patent/DE10337484B4/de not_active Expired - Fee Related
-
2004
- 2004-08-12 EP EP04764062A patent/EP1654068B1/fr not_active Expired - Lifetime
- 2004-08-12 JP JP2006522991A patent/JP2007502399A/ja active Pending
- 2004-08-12 DE DE502004002800T patent/DE502004002800D1/de not_active Expired - Lifetime
- 2004-08-12 CN CNB2004800232624A patent/CN100428998C/zh not_active Expired - Lifetime
- 2004-08-12 AT AT04764062T patent/ATE352374T1/de not_active IP Right Cessation
- 2004-08-12 WO PCT/EP2004/009063 patent/WO2005016534A1/fr not_active Ceased
-
2006
- 2006-02-14 US US11/353,681 patent/US7900850B2/en active Active
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2005016534A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100428998C (zh) | 2008-10-29 |
| JP2007502399A (ja) | 2007-02-08 |
| EP1654068B1 (fr) | 2007-01-24 |
| DE10337484A1 (de) | 2005-03-24 |
| DE10337484B4 (de) | 2005-05-25 |
| DE502004002800D1 (de) | 2007-03-15 |
| US7900850B2 (en) | 2011-03-08 |
| ATE352374T1 (de) | 2007-02-15 |
| US20060147313A1 (en) | 2006-07-06 |
| CN1835804A (zh) | 2006-09-20 |
| WO2005016534A1 (fr) | 2005-02-24 |
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