EP1259325A1 - Dispositif de microdosage pour distribution definie de volumes reduits de liquide, fermes en soi - Google Patents

Dispositif de microdosage pour distribution definie de volumes reduits de liquide, fermes en soi

Info

Publication number
EP1259325A1
EP1259325A1 EP01919276A EP01919276A EP1259325A1 EP 1259325 A1 EP1259325 A1 EP 1259325A1 EP 01919276 A EP01919276 A EP 01919276A EP 01919276 A EP01919276 A EP 01919276A EP 1259325 A1 EP1259325 A1 EP 1259325A1
Authority
EP
European Patent Office
Prior art keywords
channel
microdosing device
bypass
opening cross
section
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.)
Withdrawn
Application number
EP01919276A
Other languages
German (de)
English (en)
Inventor
Jens Albert
Rainer BRÄUTIGAM
Thomas Henkel
Günter Mayer
Andreas Schober
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institut fuer Physikalische Hochtechnologie eV
Original Assignee
Institut fuer Physikalische Hochtechnologie eV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institut fuer Physikalische Hochtechnologie eV filed Critical Institut fuer Physikalische Hochtechnologie eV
Publication of EP1259325A1 publication Critical patent/EP1259325A1/fr
Withdrawn legal-status Critical Current

Links

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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1039—Micropipettes, e.g. microcapillary tubes

Definitions

  • Microdosing device for the defined delivery of small, closed liquid volumes
  • the invention relates to a dosing device for the defined delivery of small, self-contained liquid volumes, which enables the generation of individual drops with volumes in the range from 10 nl to 3 ⁇ l.
  • Such pipetting systems are used to fill cell compartments, e.g. Nanotiter plates, in particular with changing reagents and for the production of biochips with spot sizes, in particular in the range from 0.2 mm to 2 mm, application.
  • microdosing devices for the same purpose as the present invention are already known.
  • DE 197 06 513 AI, DE 198 02 367 Cl and DE 198 02 368 Cl describe microdosing devices in which a pressure chamber is provided which is delimited by a membrane-like displacer, the displacer being provided with an actuating device with the aid of which the dispensing is carried out a defined amount of liquid from the drain chamber is effected via an outlet opening.
  • These modules are micromechanically manufactured using these solutions.
  • a piezo stack actuator is used for the actuating device.
  • the solutions described above also require integrated valves in order to prevent the liquid from flowing back out of the outlet channel.
  • microdosing device is known: "Mikrodostechnik", company typeface from microdrop GmbH, Norderstedt, 1995, in which a thin glass capillary is enclosed by a piezoelectric actuator which, when voltage is applied, causes a contraction of the capillary section encompassed by it and thus defines a defined one Volume of liquid displaced from the capillary.
  • the integration density or adjacent arrangement on the media-dispensing channels is limited if several dispensing channels are provided. Furthermore, the design of the above-mentioned devices makes cleaning them difficult, particularly when changing media.
  • the invention is based on the object of specifying an inexpensive microdosing device which enables a defined delivery of small, self-contained liquid volumes with a liquid volume which can be freely selected from volume part to volume part in a relatively large range, without thereby influencing the dwell time of the dispenser moving relative to the settling area and which is free from the disadvantages of the prior art.
  • the object is achieved by the characterizing features of the first claim.
  • Advantageous embodiments are covered by the subordinate claims.
  • the essence of the invention consists in the structural decoupling of pressure-generating means from the actual dispensing means.
  • FIG. 2 a first embodiment of the invention in a transparent perspective illustration
  • FIG. 3 a a base body of a second embodiment of the invention in a transparent perspective illustration
  • FIG. 3 b a special, 3a capillary formation to be used in a basic body according to FIG. 3a
  • FIG. 3c the assemblies according to FIGS. 3a and 3b in the assembled state
  • 4 shows a possibility of integrating several microdosing devices in a common carrier and
  • FIG. 5 shows, by way of example, the volume of the liquid dispensed from a resting capillary as a function of that for the generation of a drain pulse for various
  • Figures la and lb show possibilities of pneumatic pressurization of the proposed microdosing device m.
  • Fig. La dl stand for a pneumatic d2 for a pressure regulator, d3 for a throttle, d4 for a pressure reservoir and s for a switching valve.
  • d5 stands for an acoustic, mechanical, magnetic or electromagnetic device to be designed according to the state of the art in Teclinik for generating a pneumatic pressure pulse.
  • FIG. 2 shows a transparent and perspective view of a first embodiment of a microdosing device m, consisting of a carrier body 1, into which a first channel 2 is introduced, which is connected at the upper end to a pressurizing agent d, the pressurizing agent d in the example shown in FIG Fig. La should contain modules enclosed by a dashed frame.
  • the switching valve s cf. FIG. 1 a
  • the channel 2 can be acted upon by a pneumatic pressure pulse.
  • the entire second channel 5 filled with the liquid to be dispensed (not shown), which in the example is fastened in channel 2 by means of a holding and sealing means 4, is either emptied all at once or only a partial amount dispensed in the form of a drop at the nozzle-shaped end 54 (not shown).
  • the liquid to be dispensed is taken up according to FIG. 2, in which the channel 5 is designed as a capillary, by simply immersing it in a container (not shown) which contains the liquid in question.
  • the inner capillary diameter of the channel 5 is 0.6 mm and in the nozzle-shaped end 54 between 50 ... 100 ⁇ m.
  • the first channel 2 is provided with a bypass 3 which brings about a pressure compensation with the surroundings, which in the example is designed as a bore through the carrier 1.
  • the opening cross-section of the channel 2, in the example with an inside diameter of 4 mm and a channel length of 4 cm, is larger than the opening cross-section of the bypass 3, which in the example is given an inside diameter of 1.2 mm.
  • the end 53 of the second channel 5 opening into the first channel 2 is arranged below the attachment for the bypass 3 and the smallest opening cross section of the channel 5, in the nozzle-shaped end 54, is smaller than the opening cross section of the bypass 5.
  • FIG. 5 shows, for a variant according to FIG.
  • the volume of the liquid dispensed from a capillary 5 based on a maximum of 5 ⁇ l as a function of the pressure specified for generating the pressure pulse by the pressure regulator d2, for example for water and the organic solvents ethanol, dimethylformamide, dimethyl sulfoxide and toluene.
  • FIG. 3a shows schematically a GmndMech a second embodiment of the invention in a transparent perspective view, in which on both sides of the first channel 2, which is connected to a pressurizing means d (see Fig. 3b), channel sections 22, 23 are provided which have openings are connected to the channel 2 and face each other in alignment.
  • An interrupted capillary path 51, 52 can be introduced into these channel sections 22, 23, the capillary paths 51, 52 being connected to a sealing and deformable membrane 6 in the interrupted area.
  • the interrupted capillary paths are formed by two tubular capillaries, which are connected to one another and spaced from one another via a tubular membrane 6.
  • said membrane area 6 is positioned such that it comes to lie within the first channel 2 and is sealed by the channel sections 22, 23 outside the deformable membrane area 6, only the deformable membrane area 6 can be acted upon with a pneumatic pressure pulse that can be applied to channel 2.
  • the channel 2 is again provided with a bypass 3 analogous to the embodiment according to FIG. 2.
  • the largest inner diameter of the channel 2 is 4 mm
  • the inner diameter of the capillary paths 51, 52 is determined analogously to FIG. 2
  • the outflow-side capillary path 51 is in turn to be made nozzle-shaped (not shown).
  • the inner diameter of the bypass 3 is 1.8 mm.
  • the inlet-side part of the capillary path 52 is connected to a liquid reservoir or inlet f, so that there is a continuous supply of liquid to the liquid to be dispensed.
  • the outflow-side capillary path 51 can be shorter than that shown in FIG. 2 and is 25 mm in the example, since due to the constant supply of liquid, the entire liquid to be dispensed no longer has to be taken up through this section.
  • Fig. 3c With an embodiment according to Fig. 3c With a nozzle cross-section between 50 ... 200 ⁇ m in the capillary outlet area 51 and pneumatic pressure pulses, drop volumes in a range from 30 nl to 2 ⁇ l can be generated.
  • a miniaturization of a device according to FIGS. 3 and arrangements of several such devices next to one another is within the scope of the invention and is easier to achieve due to the permanent fluid supply than according to FIG. 2.
  • a channel (2) is connected to melter pressure-compensating bypasses (3), the sum of the minimum opening cross sections of the bypasses (3) being a maximum of twice the opening cross section of the channel (2).
  • FIG. 1 A possibility of integrating a plurality of microdosing devices in a common carrier 1 is indicated schematically in FIG.
  • the channels 2 and 5 to be provided are congruent in each of two platelet-shaped carrier bodies 11, 12 (cf. the lower part of FIG. 4) by means of microsystem technology methods, with recesses for forming the per channel in one of the carrier bodies, here 11 2 bypasses are to be provided.
  • the two platelet-shaped carrier bodies 11, 12 can be connected to one another, for example, by anodic bonding.
  • the basic design of the individual assemblies 2, 3 and 5 in this example essentially follows the exemplary embodiment according to FIG.
  • each of the channels 2 should be provided with a separate pressurizing means.
  • the present invention enables e.g. when used according to FIG. 1 a, after calibration, the setting of the desired drop volume over a wide volume range exclusively via the pressure specification with which the pressure reservoir is acted upon.
  • the determination of the linear calibration function over wide ranges on the basis of the dependence of the drop volume on the pressure specification (cf. FIG. 5) takes place experimentally for the corresponding reagents in the device-specific experiment and is then available until the device configuration is changed.
  • the use of non-linear calibration functions can further increase the accuracy.
  • the calculation of the calibration function on the basis of the solvent parameters density, viscosity, surface tension, various device parameters and empirical device parameters is possible.
  • the user By integrating the calibration function and transferring the reagent parameter set to a control software, the user only needs to specify the drop volume to be dispensed. The operator's operating effort is thus reduced to the specification of the drop volumes, the target coordinates x, y, z (when coupling between the microdosing device and a positioning system) and the reagent parameters, which can be provided by an internal database.
  • microdosing device software-based control of the respective fill level of the microdosing device is possible, as a result of which the fully automatic reloading of reagent can be implemented.
  • One and the same microdosing device is thus able to dispense drops of different volumes over a large range even during a loading cycle of a drop receiving medium.
  • embodiments according to FIGS. 2 and 3 enable pipetting operations to be carried out without direct contact between the medium to be dispensed and mechanical, electromechanically active or passive assemblies or auxiliary media.
  • the proposed microdosing device thus extends the range of media and reagents accessible to the microdosing process, in particular highly reactive or highly corrosive media, such as e.g. Acid chlorides, trifluoroacetic acid, organometallic compounds such as e.g. Grignard reagents, solutions of metal amides (LDA), reducing agents, e.g.
  • deformable membrane d pressure application means dl pressure supply device d2 pressure regulator d3 throttle d4 pressure reservoir d5 acoustic, mechanical, magnetic or electromagnetic device for generating a pneumatic pressure pulse for liquid reservoir or inlet m microdosing device s switching valve

Abstract

L'invention concerne un dispositif de microdosage permettant de distribuer de manière dosée des volumes réduits de liquide, fermés en soi. L'invention vise à mettre au point un dispositif de microdosage (m) économique permettant de distribuer de manière définie des volumes de liquide, fermés en soi, avec un volume de liquide pouvant être sélectionné librement de partie en volume à partie en volume, dans une plage relativement importante, sans influer pour autant sur le temps de séjour du distributeur qui se déplace par rapport à la zone de sédimentation. A cet effet, un corps support (1) comporte au moins un premier canal (2) relié à un moyen de sollicitation en pression (d) qui sollicite le canal (2) avec une impulsion de pression pneumatique pouvant être prédéterminée de manière variable. Le canal (2) est relié à au moins une dérivation (3) compensatrice de pression. La section transversale d'ouverture minimale de la dérivation (3) correspond au plus au double de la section transversale d'ouverture du canal (2). Ledit canal (2) est muni, à l'extrémité (21) opposée à la face de sollicitation en pression, à au moins un second canal (5) recevant le liquide à distribuer, second canal dont la section transversale d'ouverture est inférieure à celle de la dérivation (3).
EP01919276A 2000-02-25 2001-02-13 Dispositif de microdosage pour distribution definie de volumes reduits de liquide, fermes en soi Withdrawn EP1259325A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10010208A DE10010208C2 (de) 2000-02-25 2000-02-25 Mikrodosiervorrichtung zur definierten Abgabe kleiner in sich geschlossener Flüssigkeitsvolumina
DE10010208 2000-02-25
PCT/EP2001/001572 WO2001062387A1 (fr) 2000-02-25 2001-02-13 Dispositif de microdosage pour distribution definie de volumes reduits de liquide, fermes en soi

Publications (1)

Publication Number Publication Date
EP1259325A1 true EP1259325A1 (fr) 2002-11-27

Family

ID=7633260

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01919276A Withdrawn EP1259325A1 (fr) 2000-02-25 2001-02-13 Dispositif de microdosage pour distribution definie de volumes reduits de liquide, fermes en soi

Country Status (5)

Country Link
US (1) US20030003027A1 (fr)
EP (1) EP1259325A1 (fr)
JP (1) JP2003523284A (fr)
DE (1) DE10010208C2 (fr)
WO (1) WO2001062387A1 (fr)

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DE10255595A1 (de) * 2002-11-26 2004-06-03 Cybio Ag Mehrkanaldosiervorrichtung mit automatischer Kalibrierung
US7344002B2 (en) 2003-03-31 2008-03-18 Minebea Co., Ltd. Method and apparatus for filling the bearing gap of a hydrodynamic bearing with a lubricant
DE10315222B3 (de) * 2003-03-31 2005-02-24 Minebea Co., Ltd. Verfahren und Vorrichtung zur Einbringung von Schmiermittel bei einem hydrodynamischen Lager
US8383059B2 (en) 2005-09-30 2013-02-26 University Of Utah Research Foundation Microfluidic interface for highly parallel addressing of sensing arrays
DE102008039117B3 (de) * 2008-08-21 2010-05-20 Institut für Bioprozess- und Analysenmesstechnik e.V. Anordnung und Verfahren zum Erzeugen, Manipulieren und Analysieren von Kompartimenten
US8757511B2 (en) 2010-01-11 2014-06-24 AdvanJet Viscous non-contact jetting method and apparatus
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
US10300450B2 (en) 2012-09-14 2019-05-28 Carterra, Inc. Method and device for depositing a substance on a submerged surface
CN111803275A (zh) * 2019-04-10 2020-10-23 上海交通大学医学院附属第九人民医院 一种微量注射装置
LU501473B1 (en) * 2022-02-15 2023-08-16 Dispendix Gmbh Method for setting a volume of liquid to be dispensed
LU501475B1 (en) * 2022-02-15 2023-08-16 Dispendix Gmbh Method for determining a function for determining a volume of liquid to be dispensed
LU501476B1 (en) * 2022-02-15 2023-08-16 Dispendix Gmbh Method for determining a function for determining a volume of liquid to be dispensed
LU501474B1 (en) * 2022-02-15 2023-08-17 Dispendix Gmbh Method for determining a volume of liquid arranged in a receptacle
LU501663B1 (en) * 2022-03-15 2023-09-20 Dispendix Gmbh Method for determining a function for determining a volume of liquid to be dispensed
LU501823B1 (en) * 2022-04-10 2023-10-10 Dispendix Gmbh Method for determining a function for determining a volume of liquid to be dispensed
LU501825B1 (en) * 2022-04-10 2023-10-10 Dispendix Gmbh Method for setting a volume of liquid to be dispensed by using a function
LU501824B1 (en) * 2022-04-10 2023-10-10 Dispendix Gmbh Method for setting a volume of liquid to be dispensed from a receptacle
LU502213B1 (en) * 2022-06-02 2023-12-04 Dispendix Gmbh Method for Determining a Volume of Liquid dispensed from a Receptacle
CN115106143A (zh) * 2022-06-29 2022-09-27 合肥瀚海星点生物科技有限公司 一种高精度电动微量液体移液器

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Also Published As

Publication number Publication date
DE10010208A1 (de) 2001-09-13
WO2001062387A1 (fr) 2001-08-30
US20030003027A1 (en) 2003-01-02
DE10010208C2 (de) 2002-02-07
JP2003523284A (ja) 2003-08-05

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