EP1614469B1 - Méthode et dispositif pour distribuer un liquide avec une aiguille de pipette - Google Patents
Méthode et dispositif pour distribuer un liquide avec une aiguille de pipette Download PDFInfo
- Publication number
- EP1614469B1 EP1614469B1 EP05075977A EP05075977A EP1614469B1 EP 1614469 B1 EP1614469 B1 EP 1614469B1 EP 05075977 A EP05075977 A EP 05075977A EP 05075977 A EP05075977 A EP 05075977A EP 1614469 B1 EP1614469 B1 EP 1614469B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- needle
- pulse
- pipetting needle
- tip
- signal
- 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.)
- Expired - Lifetime
Links
Images
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
- B01L3/021—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
- B01L3/0234—Repeating pipettes, i.e. for dispensing multiple doses from a single charge
-
- 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
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
-
- 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
- B01L2400/0493—Specific techniques used
- B01L2400/0496—Travelling waves, e.g. in combination with electrical or acoustic forces
Definitions
- the invention concerns a method for dispensing a liquid volume according to claim 1.
- the invention further concerns a micropipetting apparatus according to of claim 5.
- Pipetting of liquids is an important function of automatized analysis of samples examined for the purposes of medical diagnosis. Mastering of the pipetting operations is a basic condition for performing analysis which are correct, fast, cheap and ecological. There is a need for a pipetting apparatus which is able to pipette with the required accuracy liquid volumes in the nanoliter and microliter range.
- Dispensing of very small liquid volumes requires contact of the pipetting needle with a solid surface or with another liquid to which the dispensed volume is added. This is so because the adhesion forces which retain the small volume to be dispensed to the pipetting needle are larger than the weight of that small liquid volume. This weight alone is thus not sufficient for releasing a drop attached by adhesion forces to the tip of a pipetting needle.
- prior art automatic pipetting apparatus of analyzers used for medical diagnosis a drop of a liquid to be dispensed is therefore brought into contact with and thereby delivered into another liquid, which can be a sample or a reagent. In order to avoid erroneous analysis results, it is necessary to clean the pipetting needle after each such contact with liquid in a container and this requires a lot of time.
- Fig. 1 shows a prior art dispensing of very small aliquots of a liquid to a plurality of different vessels.
- a pipetting needle 11 is used for taking a sample of liquid contained in a vessel 12 and for successively dispensing aliquots of that sample to different vessels 13 and 14.
- the tip needle 11 has to contact a liquid contained in the vessel 13, 14 which receives the aliquot.
- the needle 11 has to be cleaned after each such dispensing, before dispensing an aliquot in a different vessel.
- Fig. 1 shows cleaning positions 15 and 16 of the pipetting needle.
- arrows represent the sense of motion of the pipetting needle during the above-mentioned dispensing operations.
- Drops can be dispensed for instance like in inkjet printers, wherein a pressure pulse is generated within a liquid and this pulse propagates towards a nozzle which closes one end of a container which contains the liquid to be dispensed. Due to the reduction of the cross-section at the transition from the interior of the container to the nozzle, a small liquid volume is strongly accelerated and this allows to release through the nozzle one drop of liquid from the container.
- the size of a drop generated by the inkjet principle lies in a range going from 5 to 500 picoliter and depends from the properties of the liquid and from the size of the nozzle. Drops generated only by the weight of the drop to be dispensed are much larger.
- a nozzle of the type used in inkjet printers cannot be a part of a pipetting needle of an analyzer for analyzing samples for the purposes of medical analysis, because the structure of the pipetting needle should allow the required sufficient cleaning of the pipetting needle as often as required the presence of a nozzle in the structure of the pipetting needle would render this impossible.
- Other requirements the pipetting needle should fulfill are:
- U.S. Patent Specification No. 6,033,388 discloses a method and an apparatus of the kind defined by claims 1 and 5 respectively. According to U.S. Patent Specification No. 6,033,388 acoustic radiation energy pulsed waves generated by a transducer are applied to one end of a hollow needle which is opposite to the discharge end of the needle and focusing of those waves is achieved by a tapering of a portion of the the needle, the side wall of that portion of the needle having a thickness which decreases towards the discharge end of the needle.
- An aim of the invention is to provide a method and an apparatus of the above mentioned kind which enable a contact-free dispensing of liquid drops from the tip of a pipetting needle, and which in particular allow the use of a pipetting needle having any of various shapes and dimensions suitable for use as part of a an analyzer system for analyzing samples for the purposes of medical analysis, and which can be properly cleaned by washing it with conventional washing means and which is suitable for piercing a closure of a vessel.
- a method according to the invention is described hereinafter with reference to Figures 2 to 12. This method is suitable for dispensing a liquid volume into a vessel by means of a pipetting needle and without any contact between said needle and a liquid contained in said vessel.
- a volume of liquid 17 corresponding to the volume of a drop to be dispensed is formed at the tip 22 of a pipetting needle 11 by exerting pressure on the liquid contained in the interior of the pipetting needle. Adhesion forces retain the drop so formed attached to the tip 22 of the pipetting needle 11.
- the volume 17 is ejected from the tip of needle 11 as a drop 18 which is delivered to and thereby added to a liquid contained in a vessel 13. It should be noted that drop 18 is delivered without any contact between needle 11 and a liquid contained in vessel 13.
- Fig. 3 illustrates a successive dispensing of drops 18, 19 to different vessels 13, 14 respectively, by the method represented in Fig. 2.
- the invention makes use of the fact that the tubular wall of the pipetting needle 11 is a dispersive medium for the transmission of mechanical waves. Due to the mechanical wave propagation behaviour of the pipetting needle a mechanical wave which is applied at a first point (excitation point) of the pipetting needle and propagates through the tubular wall of the needle travels towards the tip of the needle at a speed which depends on the frequency of that wave.
- a simple beam e.g. a steel beam having a radius of 0.005 m
- Timoshenko Beam theory see Graff, K. F., Wave Motion in Elastic Solids, Ohio State University Press, 1975
- the phase speed of a mechanical wave that propagates through the beam is a function of the frequency of the mechanical wave.
- Fig. 18 shows the dispersion characteristics of the above-mentioned Timoshenko beam, i.e. how the phase speed varies in function of the frequency in such a case.
- mechanical waves which have higher frequencies propagate through the beam with higher phase speeds and have also higher group velocities than mechanical waves which have lower frequencies. This means that mechanical waves which have higher frequencies travel faster than mechanical waves which have lower frequencies.
- a mechanical excitation which corresponds to the signal represented by Fig. 20.
- Such a signal is computed using the dispersion characteristics shown by Fig. 18 and in the frequency space using well known methods based on the Fourier Transform described e.g. by Doyle, J.F., Wave Propagation in Structures, Springer, New York, 1989 .
- Fig. 20 shows that the low frequency components of the excitation signal have to be sent off first, because their wave speed is smaller.
- This is the basic principle used according to the invention for focusing a pulse using the dispersion characteristics of a mechanical structure: a relatively long pulse is transformed by the dispersion characteristics of the beam into a short pulse that can be used e.g. for releasing a drop as proposed by the instant invention.
- the dispersion characteristics necessary for computing the excitation signal can be taken from any book of wave propagation, e.g. Graff, K. F., Wave Motion in Elastic Solids, Ohio State University Press, 1975.
- a tube there are several propagation modes and each mode has its own dispersion characteristics. This property can be used in addition for obtaining the desired focusing effect.
- An additional focusing effect is obtainable by effecting suitable time delays of pulses of the various modes with respect to each other and thereby obtaining an overlap of pulses corresponding to the various modes at a desired location.
- pulses of several modes of propagation having each their individual mechanical wave propagation behaviour are focused and superimposed at the tip of the pipetting needle (11). This is achieved for instance by effecting suitable time delays of pulses of the various modes with respect to each other and thereby obtain an overlap of pulses corresponding to the various modes and a focusing of the energy of those pulses at the tip of the pipetting needle (11) .
- the portion of the pipetting needle used according to the invention for the above mentioned transmission of mechanical waves is shown in Figures 4 to 9. This portion has the shape of a capillary tube.
- a suitable composite mechanical excitation pulse is applied at a point 24 of the pipetting needle which lies at some distance from the needle delivery tip 22 from which the drops are ejected.
- the latter excitation pulse and the mechanical system comprising the needle 11, the liquid in the needle and the means for generating the excitation pulse, e.g. a piezoelectric transducer connected to the needle, are so configured that the excitation pulse has frequency components which arrive simultaneously to the drop delivery tip 22 of the needle and thereby provide a maximum of mechanical energy at that tip.
- the latter configuration is such that transmission of the excitation pulse by the mechanical system mentioned above focuses the mechanical wave at the tip 22 of the pipetting needle and reflection of the focused wave at that tip causes ejection of a drop which was held there by adhesion forces.
- a drop 17 is formed at the delivery tip 22 of the pipetting needle 11 by pressing a predetermined liquid volume out of the needle and thereby forming a liquid meniscus at the delivery tip 22 of the pipetting needle.
- the above described method for dispensing a liquid thus essentially comprises
- the ejection of the drop is achieved by mechanically exciting the needle by means of an excitation pulse having a composition that focuses a pulsed wave at the tip of said pipetting needle.
- an excitation pulse having a composition that focuses a pulsed wave at the tip of said pipetting needle.
- a superposition of a focused incident wave with a reflected wave at the delivery tip of the pipetting needle causes ejection of the drop from the tip.
- a suitable composition of the excitation pulse is obtained by a simulation process.
- the wave propagation of a desired focused pulse in a system comprising a needle filled with a liquid and a piezoelectric actuator mechanically connected with the needle is simulated by means of finite difference method (FDM).
- FDM finite difference method
- the FDM code is programmed with second order central differences, a so called staggered grid being used for discretization in space and time.
- the liquid is modeled as an acoustical fluid. In this way the behavior of the complete system can be simulated.
- the excitation pulses necessary for the desired energy focusing are computed making use of a time reversal method.
- the result of the above mentioned calculation is the electrical signal 26 to be applied to the piezoelectric transducer.
- This signal is generated by a function generator.
- a piezoelectric tube with electrodes on its major surfaces (radial electric field) and radial polarization generates mainly radial displacements.
- a piezoelectric tube with electrodes on its major surfaces (radial electric field) and axial polarization generates mainly axial displacements.
- Generation of the desired displacements in the pipetting needle can thus be obtained by election of a suitable piezoelectric transducer.
- Fig. 17 shows an example of the wave shape of excitation pulse signal 26 obtained as described above by simulation of the wave propagation in the tubular body of the needle and by time reversal of the signal recorded in that simulation.
- the obtention of the latter excitation pulse signal 26 thus take into account the complete wave propagation behavior of that tubular body, all wave propagation modes in the frequency range used and their frequency dependent propagation speeds.
- a method for generating an excitation pulse signal 26 that has a composition suitable for focusing the energy applied by that pulse to the pipetting needle is described as follows. To simplify the description and make it easier to understand the method is described for the simplified case of a pipetting needle which has the shape of simple empty tube, which does not contain any liquid and which is not mechanically coupled with any electromechanical transducer. A FDM code of the above mentioned case is written for this case and is used for the simulation. Three Hanning pulses comprising each five periods of their central frequencies of 0.5 MHz, 1.2 MHz and 2.7 MHz are symmetrically superposed in order to form a desired pulse 21 shown by Fig. 10 which should be the pulse resulting of focusing the excitation pulse applied to the needle.
- this desired pulse 21 is applied at the spot 22, where the mechanical pulses should be focused in the real experiment, and a signal 25 shown by Fig. 11 is recorded at the spot 24, where the mechanical excitation pulse is applied to the needle in the real experiment.
- Time reversal of recorded signal 25 and selection of a portion of this signal with a suitable time window provides the excitation pulse 26.
- the time window is so chosen that only the first arriving pulses are considered, but not those already reflected.
- An excitation pulse 26 obtained in the latter way is applied at spot 24 of the needle and this provides the desired focused pulse 21 shown in Fig. 12.
- the first mode is a torsional mode.
- the second mode is a longitudinal mode.
- Fig. 11 shows four pulses of different modes which reach spot 24 in Fig. 5 and which are the result of applying a pulse 21 at spot 22 in Fig. 5.
- excitation pulse 26 consists of four pulses.
- Fig. 12 shows six pulses that arise at the right end 22 of the capillary tube when a mechanical excitation corresponding to excitation pulse 26 is applied at spot 24. The latter six pulses result from the four pulses of the excitation pulse 26, because above 2 MHz there are 2 propagation modes.
- the method just described above is just a simplified example of a method for focusing mechanical pulses.
- a pipetting needle For the purpose of releasing drops from the delivery tip of a pipetting needle not only the behavior of a capillary tube (pipetting needle), but also the behavior of a piezoelectric transducer used for applying the mechanical pulses is simulated. Simulation of the behavior of a liquid in the interior of the needle is less important than simulation of the behavior of the capillary tube and the piezoelectric transducer, because the liquid in the needle has less influence on the process for releasing a drop by the above described method.
- a suitable FDM code of the above mentioned kind is also available for performing a simulation of the behavior of the capillary tube and the piezoelectric transducer for the propagation of a mechanical pulse applied by the transducer to the capillary tube. If the simulation includes simulation of the behavior of the piezoelectric transducer, a voltage would be recorded that corresponds to the displacements shown in Fig. 11.
- a first embodiment of a micropipetting apparatus according to the invention is described hereinafter with reference to Figures 13 and 14.
- This micropipetting apparatus is suitable for dispensing a liquid volume into a vessel by means of a pipetting needle and without any contact between said needle and a liquid contained in said vessel.
- a micropipetting apparatus comprises a pipetting needle 11, a needle holder 31, an electromechanical transducer 32, a generator 33 for generating electrical signals, a connecting piece 34 which fluidically connects needle 11 with a conduit 35 which connects needle 11 with a source of positive or negative pressure, a transport system 36 for transporting needle holder 31 and a control unit 37 for controlling the operation of the entire system.
- Needle 11 has a substantially constant cross-section over the portion thereof that ends in a delivery tip 22 and that portion extends over more than one half of the total length of needle 11.
- Electromechanical transducer 32 is e.g. a piezoelectric transducer mechanically connected pipetting needle 11. This piezoelectric transducer comprises one or more piezoelectric elements.
- Transport system 36 comprises an arm 38 which carries needle holder 31.
- Fig. 14 shows a cross-sectional view of arm 38, needle holder 31, electromechanical transducer 32 and of a portion of needle 11.
- Signal generator 33 generates an excitation pulse signal and applies this signal to piezoelectric transducer 32 for mechanically exciting pipetting needle 11 at an excitation point 24 with an excitation pulse 26 that propagates through needle 11 and is focused at the end tip 22 thereof (as shown in Figures 8 and 9). The latter mechanical excitation thereby causes release of a drop from tip 22 of needle 11.
- composition of the excitation pulse 26 is adapted to the length and the wave propagation characteristic of the portion of needle 11 that has a substantially constant cross-section.
- piezoelectric element is radially polarized.
- piezoelectric element is axially polarized.
- the composition of excitation pulse 26 signal applied to piezoelectric transducer 32 is such that it causes a mainly radial displacement of liquid within said needle.
- composition of excitation pulse 26 signal applied to piezoelectric transducer 32 is such that it causes a mainly axial displacement of liquid within said needle.
- the excitation signal 26 applied at the excitation point 24 of needle 11 is generated by a method as described above with reference to Figures 4-12.
- the dimensions of the pipetting needle shown in Fig. 15 are as follows: Dimension Size in millimeter A1 69 L1 86 L2 5 L3 9 D1 0.9 D2 1.5 D3 3 D4 5 L4 13.5 L5 0.5 D5 0.6
- the tip 23 of needle has the cylindrical shape shown and that tip is shown to have a diameter D5.
- Another embodiment of the pipetting needle shown in Fig. 16 has a similar shape and dimensions, but the tip of the needle has a sharp end which is suitable for piercing a closure of a vessel.
Landscapes
- Health & Medical Sciences (AREA)
- Clinical Laboratory Science (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Sampling And Sample Adjustment (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
Claims (11)
- Procédé de distribution d'un volume de liquide dans un récipient à l'aide d'une aiguille de pipette et sans aucun contact entre ladite aiguille et un liquide contenu dans ledit récipient, ledit procédé comprenant(a) la formation d'une goutte (17) au niveau de la pointe de distribution (22) de l'aiguille de pipette (11), ladite goutte étant retenue au niveau de la pointe par des forces d'adhérence, et(b) l'éjection de ladite goutte (17) depuis ladite pointe (22) en focalisant une onde mécanique au niveau de ladite pointe de l'aiguille de pipette (11), ladite focalisation étant réalisée en excitant un transducteur électromécanique (32) avec un signal d'impulsion d'excitation électrique (26) et en appliquant ce signal audit transducteur électromécanique (32) afin d'exciter mécaniquement ladite aiguille de pipette (11) avec une impulsion d'ondes mécaniques qui se propagent dans ladite aiguille, ledit procédé étant caractérisé en ce queladite impulsion possède une composition prédéterminée calculée pour être focalisée au niveau de la pointe de ladite aiguille de pipette par le comportement de propagation d'ondes mécaniques de celle-ci, une superposition d'une onde incidente focalisée avec une onde reflétée au niveau de la pointe de l'aiguille de pipette provoquant l'éjection de ladite goutte (17) depuis ladite pointe.
- Procédé selon la revendication 1, dans lequel ledit signal d'impulsion d'excitation (26) est adapté à la longueur et au comportement de propagation d'ondes de ladite aiguille de pipette (11).
- Procédé selon la revendication 1, dans lequel les impulsions de plusieurs modes de propagation d'ondes mécaniques ayant chacune leur comportement de propagation individuel sont focalisées et superposées au niveau de la pointe de l'aiguille de pipette (11).
- Procédé selon l'une quelconque des revendications 1 à 3, dans lequel ladite impulsion d'excitation (26) est générée en(a) simulant, à l'aide d'un procédé à différence finie, la propagation d'une impulsion mécanique au sein de la paroi d'une partie d'une aiguille de pipette qui possède la forme d'un tube capillaire, ladite impulsion étant appliquée lors de la simulation au niveau du point (22) auquel, pendant l'expérience réelle, une impulsion focalisée doit être générée afin d'éjecter une goutte (17) formée au niveau de la pointe de distribution (22) de ladite aiguille (11) et reliée à celle-ci par des forces d'adhérence,(b) enregistrant un signal d'impulsion électrique (25) qui correspond aux impulsions mécaniques qui, lors de la simulation, ont lieu au niveau du point (24) auquel l'impulsion d'excitation mécanique doit être appliquée à ladite aiguille de pipette (11) dans la réalité, et(c) en calculant un signal d'impulsion d'excitation (26) à appliquer en réalité audit transducteur piézoélectrique (32), ce dernier signal d'impulsion d'excitation étant calculé par une inversion temporelle dudit signal enregistré (25) obtenu à l'étape (b),(d) et en excitant le transducteur piézoélectrique avec ledit signal d'impulsion afin d'exciter mécaniquement l'aiguille de pipette avec une impulsion d'ondes qui se propagent dans ladite aiguille et se focalisent au niveau de la pointe de celle-ci.
- Appareil de micro-pipetage destiné à distribuer un volume de liquide situé dans un récipient à l'aide d'une aiguille de pipette et sans aucun contact entre ladite aiguille et un liquide contenu dans ledit récipient, ledit appareil comprenant(a) une aiguille de pipetage (11) ayant une première extrémité qui comprend une pointe de distribution et une seconde extrémité qui est reliée à une source de pression positive ou négative,(b) un transducteur électromécanique (32) mécaniquement relié à ladite aiguille de pipetage (11) au niveau d'une première partie de celui-ci qui comprend ladite seconde extrémité de l'aiguille de pipetage,
une seconde partie de l'aiguille s'étendant entre ladite première partie et ladite pointe de distribution, et(c) un moyen de génération de signaux électriques (33) destiné à générer un signal d'impulsion d'excitation (26) et à appliquer ce signal audit transducteur électromécanique (32) afin d'exciter mécaniquement ladite aiguille de pipetage (11) avec une impulsion d'ondes mécaniques qui se propagent dans ladite aiguille,ledit appareil étant caractérisé en ce que
ledit moyen de génération de signaux électriques (33) génère une impulsion ayant une composition prédéterminée calculée pour être focalisée au niveau de la pointe de celui-ci par le comportement de propagation d'ondes mécaniques de ladite aiguille de pipetage, ladite excitation mécanique provoquant ainsi l'éjection d'une goutte (17) formée sur la pointe de distribution de ladite aiguille de pipetage. - Appareil de micro-pipetage selon la revendication 5, dans lequel ledit moyen de génération de signaux électriques (33) génère un signal d'impulsion d'excitation (26) qui est adapté à la longueur et au comportement de propagation d'ondes mécaniques de ladite aiguille de pipetage (11).
- Appareil de micro-pipetage selon la revendication 5, dans lequel ledit transducteur électromécanique (32) est un transducteur piézoélectrique.
- Appareil de micro-pipetage selon la revendication 7, dans lequel ledit transducteur piézoélectrique (32) est radialement polarisé.
- Appareil de micro-pipetage selon la revendication 7, dans lequel ledit transducteur piézoélectrique (32) est axialement polarisé.
- Appareil de micro-pipetage selon l'une quelconque des revendications 7 à 9, dans lequel ledit signal d'impulsion d'excitation (26) appliqué audit transducteur piézoélectrique (32) est configuré de telle sorte qu'il provoque un déplacement principalement radial du liquide dans ladite aiguille (11).
- Appareil de micro-pipetage selon l'une quelconque des revendications 7 à 9, dans lequel ledit signal d'impulsion d'excitation (26) appliqué audit transducteur piézoélectrique (32) est configuré de telle sorte qu'il provoque un déplacement principalement axial du liquide dans ladite aiguille (11).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05075977A EP1614469B1 (fr) | 2004-05-14 | 2005-04-25 | Méthode et dispositif pour distribuer un liquide avec une aiguille de pipette |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04076436A EP1604741A1 (fr) | 2004-05-14 | 2004-05-14 | Methode et dispositif pour dispersion des fluides avec une aiguille de pipette |
| EP05075977A EP1614469B1 (fr) | 2004-05-14 | 2005-04-25 | Méthode et dispositif pour distribuer un liquide avec une aiguille de pipette |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP1614469A2 EP1614469A2 (fr) | 2006-01-11 |
| EP1614469A3 EP1614469A3 (fr) | 2006-03-22 |
| EP1614469B1 true EP1614469B1 (fr) | 2007-09-19 |
Family
ID=35464438
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP05075977A Expired - Lifetime EP1614469B1 (fr) | 2004-05-14 | 2005-04-25 | Méthode et dispositif pour distribuer un liquide avec une aiguille de pipette |
Country Status (1)
| Country | Link |
|---|---|
| EP (1) | EP1614469B1 (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107754963A (zh) * | 2017-10-31 | 2018-03-06 | 南京航空航天大学 | 超声移液器 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6003388A (en) * | 1997-09-17 | 1999-12-21 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | System for manipulating drops and bubbles using acoustic radiation pressure |
| US6296811B1 (en) * | 1998-12-10 | 2001-10-02 | Aurora Biosciences Corporation | Fluid dispenser and dispensing methods |
| US6232129B1 (en) * | 1999-02-03 | 2001-05-15 | Peter Wiktor | Piezoelectric pipetting device |
| US6874699B2 (en) * | 2002-10-15 | 2005-04-05 | Wisconsin Alumni Research Foundation | Methods and apparata for precisely dispensing microvolumes of fluids |
-
2005
- 2005-04-25 EP EP05075977A patent/EP1614469B1/fr not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1614469A2 (fr) | 2006-01-11 |
| EP1614469A3 (fr) | 2006-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7354141B2 (en) | Acoustic assessment of characteristics of a fluid relevant to acoustic ejection | |
| US6938995B2 (en) | Acoustic assessment of fluids in a plurality of reservoirs | |
| CN101035681B (zh) | 推断液滴声辐射脉冲的参数的方法和声发射系统 | |
| CA2505216C (fr) | Methode et dispositif de distribution d'un liquide au moyen d'une aiguille de pipettage | |
| EP0903563B1 (fr) | Dispositif pour la détection et/ou la surveillance d'un niveau prédéterminé dans un récipient | |
| WO2009124290A1 (fr) | Procédés et systèmes de couplage ultrasonique en utilisant la pression des rayons ultrasoniques | |
| US20250018387A1 (en) | Focused acoustic radiation for the ejection of subwavelength droplets | |
| US20040119793A1 (en) | Acoustic assessment of fluids in a plurality of reservoirs | |
| EP3620787B1 (fr) | Éjection acoustique activée par focalisation | |
| US10800170B1 (en) | Droplet ejection using focused acoustic radiation having a plurality of frequency ranges | |
| EP1614469B1 (fr) | Méthode et dispositif pour distribuer un liquide avec une aiguille de pipette | |
| US11986848B2 (en) | Acoustic droplet ejection | |
| US7281413B2 (en) | Acoustic method for determining the viscosity and/or surface tension of a liquid | |
| IE20020333A1 (en) | A method and device for dispensing of droplets |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR |
|
| AX | Request for extension of the european patent |
Extension state: AL BA HR LV MK YU |
|
| PUAL | Search report despatched |
Free format text: ORIGINAL CODE: 0009013 |
|
| 17P | Request for examination filed |
Effective date: 20060123 |
|
| AK | Designated contracting states |
Kind code of ref document: A3 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR |
|
| AX | Request for extension of the european patent |
Extension state: AL BA HR LV MK YU |
|
| RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: ROCHE DIAGNOSTICS GMBH Owner name: F. HOFFMANN-LA ROCHE AG |
|
| AKX | Designation fees paid |
Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR |
|
| GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
| GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR |
|
| REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
| REF | Corresponds to: |
Ref document number: 602005002499 Country of ref document: DE Date of ref document: 20071031 Kind code of ref document: P |
|
| REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: VENTOCILLA PATENT AG |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: PL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| NLV1 | Nl: lapsed or annulled due to failure to fulfill the requirements of art. 29p and 29m of the patents act | ||
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2293472 Country of ref document: ES Kind code of ref document: T3 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| ET | Fr: translation filed | ||
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 Ref country code: GR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20071220 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 Ref country code: PT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20080219 Ref country code: CZ Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20080119 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20071219 Ref country code: RO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| 26N | No opposition filed |
Effective date: 20080620 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MC Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20080430 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20080425 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BG Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20071219 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: ROCHE DIAGNOSTICS AG |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20080425 Ref country code: HU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20080320 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: TR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070919 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: PFA Owner name: F. HOFFMANN-LA ROCHE AG, CH Free format text: FORMER OWNER: F. HOFFMANN-LA ROCHE AG, CH |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 12 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 13 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 14 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20200327 Year of fee payment: 16 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20200325 Year of fee payment: 16 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20200320 Year of fee payment: 16 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20200317 Year of fee payment: 16 Ref country code: ES Payment date: 20200505 Year of fee payment: 16 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20200417 Year of fee payment: 16 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 20200326 Year of fee payment: 16 |
|
| REG | Reference to a national code |
Ref country code: DE Ref legal event code: R119 Ref document number: 602005002499 Country of ref document: DE |
|
| REG | Reference to a national code |
Ref country code: AT Ref legal event code: MM01 Ref document number: 373519 Country of ref document: AT Kind code of ref document: T Effective date: 20210425 |
|
| GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 20210425 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210430 Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210425 Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210430 Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210425 Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210430 Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20211103 |
|
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20220701 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210426 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20200425 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20210425 |