EP1401581A1 - Multi-channel fluid dispenser - Google Patents

Multi-channel fluid dispenser

Info

Publication number
EP1401581A1
EP1401581A1 EP02740180A EP02740180A EP1401581A1 EP 1401581 A1 EP1401581 A1 EP 1401581A1 EP 02740180 A EP02740180 A EP 02740180A EP 02740180 A EP02740180 A EP 02740180A EP 1401581 A1 EP1401581 A1 EP 1401581A1
Authority
EP
European Patent Office
Prior art keywords
channels
channel
plate
cavities
dispenser according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP02740180A
Other languages
German (de)
French (fr)
Other versions
EP1401581B1 (en
Inventor
Marc Boillat
Bart Van Der Schoot
Andreas Kuoni
Roeland Papen
Nico De Rooij
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.)
Seyonic SA
Original Assignee
Seyonic SA
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 Seyonic SA filed Critical Seyonic SA
Priority to EP02740180A priority Critical patent/EP1401581B1/en
Publication of EP1401581A1 publication Critical patent/EP1401581A1/en
Application granted granted Critical
Publication of EP1401581B1 publication Critical patent/EP1401581B1/en
Anticipated expiration legal-status Critical
Expired - Lifetime 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
    • 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

Definitions

  • the present invention relates to the production of high density miniaturized networks of samples of biological substances (oligonucleotides, DNA, ...), often designated “biochips", for their treatment.
  • Such networks are particularly useful tools in the field of molecular biology, as evidenced, in particular, by the publications "High-density oligonucleotides arrays” (AP Blanchard et Al. - Biosensors & Biolectronics, Vol. 11, N ° 6/7, pp. 686-690, 1996) and "Array of hope” (ES Lander - Nature Genetics Supplement, Vol. 21, January 1999).
  • the invention relates, more particularly, to a multi-channel fluid dispenser making it possible to withdraw liquid from a plurality of cavities formed on a reservoir tray and then to deposit a network of microdrops on a receiving tray so as to constitute a "biochip".
  • the dispenser according to the invention is of the type comprising:
  • the channels are formed by a bundle of capillary wires gathered on a print head. They are ordered all together.
  • the dispenser according to the invention is designed to respond, better than the systems of the prior art mentioned above, to the following main requirements:
  • the dispenser according to the invention is characterized in that the channels are formed in a plurality of flexible plates so as to converge from their first ends to their second ends, in that these plates are linked together by their part which has the second ends of the channels and in that each plate is formed of two polymeric sheets sealed together and one of which, at least, has a network of converging grooves forming the channels.
  • the dispenser according to the invention also has the following main characteristics:
  • the reservoir plate is closed, in a leaktight manner, by a cover through which the channels pass and the filling means are arranged so as to establish an overpressure in the space between the cover and the cavities;
  • the filling means comprise a bellows joining the cover and its tray by their periphery;
  • Each channel has a first narrowing located near its second end and a second narrowing located at this end and the expulsion means comprise a piezoelectric actuator disposed on an outer wall of the channel, between its two narrowing, and having the role of deforming it there so as to reduce the thickness of the channel;
  • the expulsion means comprise a second piezoelectric actuator identical to the first and arranged opposite it on the other outer wall of the channel;
  • the piezoelectric actuator is formed of a stack which comprises, starting from the outer wall of the channel, a lower metal electrode, an insulation layer, a layer of piezoelectric material, a new insulation layer and an upper metal electrode; finally,
  • each actuator is controlled individually.
  • FIGS. 1 and 2 represent, respectively seen from the front and from the side, a dispenser according to the invention
  • FIG. 3 shows, arranged side by side, respecting the ratio of their dimensions, a tank tray and a receiver tray;
  • FIG. 4 is a sectional view of a channel
  • FIG. 5 shows, in section, the structure of the actuator associated with each channel.
  • Figures 1 and 2 show at 10 a reservoir plate, made of rigid glass or plastic, provided with a plurality of cavities 12, arranged in a matrix, in each of which is disposed a biological liquid 14, samples of which must be deposited, in the form of micro-drops, on a miniaturized receiving tray 16, also made of glass or rigid plastic (nylon).
  • a reservoir plate made of rigid glass or plastic, provided with a plurality of cavities 12, arranged in a matrix, in each of which is disposed a biological liquid 14, samples of which must be deposited, in the form of micro-drops, on a miniaturized receiving tray 16, also made of glass or rigid plastic (nylon).
  • the reservoir tray 10 has a surface of approximately 100 cm 2 (12.5 cm x 8.5 cm) and has 384 cavities 12, having a volume of approximately 100 ⁇ l, arranged in a matrix of 16 columns of 24 rows and separated by each other, center to center, approximately 4.5 mm.
  • the receiving plate 16 has no cavities and has an area of only about 1 cm 2 (1.2 cm x 0.8 cm).
  • the device according to the invention comprises a plurality of flexible transfer plates 18 assembled together. These plates are made of polyimide, for example and have a thickness of the order of 50 to 150 ⁇ m.
  • Each plate 18 has a lower part in the form of an isosceles trapezoid 20, forming a fluidic interface, the large base of which has substantially the same length as the width of the reservoir plate 10 and is crenellated so as to end in as many end portions. 22 that the reservoir plate comprises columns of cavities 12, ie 16 in the example described. The slots are dimensioned so that the portions 22 can penetrate into the cavities 12.
  • the fluidic interface 20 in the shape of a trapezoid is extended, from its small base, by a rectangular part 24 whose length corresponds substantially to the width fe of the receiving plate 16.
  • Each flexible plate 18 is provided with a bundle of channels 26 which originate in each of its end portions 22 and terminate, parallel to each other, in the upper part 24. Typically, in the embodiment described , the channels 26 are then spaced from each other, center to center, by 0.5 mm.
  • the device according to the invention comprises as many identical plates 18 as the reservoir plate 10 comprises rows, that is 24 in the example described, the end portions 22 of each plate being intended to take place in one of the columns of the tray.
  • the flexible plates 18 are assembled, at their upper part, parallel to each other, in a frame 28, to form a printing head whose length corresponds substantially to the length L2 of the receiver plate 16 and whose width, as already mentioned, corresponds substantially to its width fe.
  • the plates could also have a base of length corresponding to the length L1 of the reservoir tray 10.
  • the reservoir tray 10 is closed, in a leaktight manner, by a cover 30 traversed , also in a sealed manner, by the flexible plates 18.
  • the sealing on the periphery is ensured by a bellows 32 whose role will appear below.
  • FIG. 4 shows, on a larger scale, the way in which the flexible plates 18 and their channels 26 are made. It appears that these plates are formed from two thin plastic sheets 34 and 36, one of which , the upper sheet 34 in the figure, was previously engraved, by any process well known to those skilled in the art, to draw the outline of the channels 26 and which are then assembled to each other by a rolling process , also well known to those skilled in the art.
  • the sheets 34 and 36 have a thickness of 25 to 50 ⁇ m, while the channels 26 have a depth of 70 to 50 ⁇ m and a width of 30 to 1000 ⁇ m.
  • the total volume of a channel is approximately 0.5 to 3 ⁇ L.
  • the plates 18 comprise, fixed on their upper sheet 34, opposite each channel 26, a piezoelectric actuator 38 whose role is to deform the sheet at this location in order to reduce the thickness of the channel.
  • the channel 26 opens to the outside of the sheet by a narrowing forming a spout 40, while, on the other side, the channel has a narrowing 42.
  • the spout 40 and the narrowing 42 have the same depth, from 10 to 40 ⁇ m, and the same width, from 40 to 90 ⁇ m. The dimensions of the narrowing may even be smaller than those of the spout.
  • FIG. 5 shows that the actuator 38 is formed of a stack which comprises, starting from the sheet 34, a lower metal electrode 44, an insulation layer 46, a layer of piezoelectric material 48, a new layer insulation 50 and an upper metal electrode 52. The two electrodes are associated with electrical conductors 54 allowing the actuator to be controlled.
  • the electrodes 44 and 52 are deposited by evaporation, while the insulation layers 46 and 50 are deposited by plasma and the piezoelectric layer 48 is deposited by vaporization using a magnetron. As shown in FIG. 1, the electrical supply conductors of the various actuators 38 lead to a control circuit 56 which, under the orders of a computer 58, ensures their excitation.
  • the assembly formed by the transfer plates 18 assembled is placed above the reservoir plate 10, the cavities 12 of which contain the liquids 14 to be transferred to the receiver plate 16.
  • the alignment is carried out so that after passing through the cover 30, each of the end portions 22 of the transfer plates 18 is located vertically in a cavity 12.
  • the ends of the plates are immersed in the liquid, the latter is sucked into the different channels 26 by capillarity.
  • the receiving plate 16 can thus receive a network of micro-drops of liquid formed of the same number of rows and columns as the reservoir plate but, as already mentioned, on a greatly reduced scale.
  • the micro-drops can have a volume of 20 pL to 1 nL.
  • the channels 26 could be subjected to the effect of two identical actuators 38 arranged face to face on the outside of each of the sheets forming the flexible plates. Such an arrangement allows better control of the direction of ejection of the drops.
  • the present description has been made with reference to a flexible plate formed from two sheets sealed together.
  • the plate could be formed from three sheets, the central sheet of which would be pierced with through openings forming the channels.

Abstract

The multi-channel fluid dispenser takes the fluid (14) at a reservoir plate (10) with a number of hollow cavities (12) and project the fluid to a receiving plate (16) as a biochip. A number of supple channels (26) are in a converging configuration, where one of their ends is extended into the hollow cavities and the other ends are gathered into a miniaturized grid. The multi-channel fluid dispenser takes the fluid (14) at a reservoir plate (10) with a number of hollow cavities (12) and project the fluid to a receiving plate (16) as a biochip. A number of supple channels (26) are in a converging configuration, where one of their ends is extended into the hollow cavities and the other ends are gathered into a miniaturized grid. The channels are filled from their ends in the hollow cavities. A droplet of the fluid is ejected from the other ends of the channels, towards the biochip, which is of glass or a rigid plastics. The channels are shaped in supple side plates (18). The fluid droplet ejection is by piezo electrical impulses.

Description

DISPENSATEUR DE FLUIDE MULTI-CANAL MULTI-CHANNEL FLUID DISPENSER
La présente invention se rapporte à la réalisation de réseaux miniaturisés à haute densité d'échantillons de substances biologiques (oligonucléotides, DNA,...), souvent désignés "biochips", en vue de leur traitement.The present invention relates to the production of high density miniaturized networks of samples of biological substances (oligonucleotides, DNA, ...), often designated "biochips", for their treatment.
De tels réseaux sont des outils particulièrement utiles dans le domaine de la biologie moléculaire, ainsi que l'attestent, notamment, les publications "High- density oligonucléotides arrays" (A. P. Blanchard et Al. - Biosensors & Biolectronics, Vol. 11 , N° 6/7, pp. 686-690, 1996) et "Array of hope" (E. S. Lander - Nature Genetics Supplément, Vol. 21 , January 1999).Such networks are particularly useful tools in the field of molecular biology, as evidenced, in particular, by the publications "High-density oligonucleotides arrays" (AP Blanchard et Al. - Biosensors & Biolectronics, Vol. 11, N ° 6/7, pp. 686-690, 1996) and "Array of hope" (ES Lander - Nature Genetics Supplement, Vol. 21, January 1999).
L'invention concerne, plus particulièrement, un dispensateur de fluide multi- canal permettant de prélever du liquide dans une pluralité de cavités ménagées sur un plateau réservoir puis d'en déposer un réseau de micro- gouttes sur un plateau récepteur de manière à constituer un "biochip".The invention relates, more particularly, to a multi-channel fluid dispenser making it possible to withdraw liquid from a plurality of cavities formed on a reservoir tray and then to deposit a network of microdrops on a receiving tray so as to constitute a "biochip".
Le dispensateur selon l'invention est du type comportant:The dispenser according to the invention is of the type comprising:
- une pluralité de canaux souples disposés en un faisceau convergent, dont les premières extrémités sont destinées à être plongées dans les cavités du plateau réservoir et dont les deuxièmes extrémités sont assemblées en un réseau miniaturisé,a plurality of flexible channels arranged in a convergent bundle, the first ends of which are intended to be immersed in the cavities of the reservoir plate and the second ends of which are assembled in a miniaturized network,
- des moyens de remplissage des canaux, à partir de leurs premières extrémités, par le liquide contenu dans les cavités, etmeans for filling the channels, from their first ends, with the liquid contained in the cavities, and
- des moyens d'expulsion d'une goutte de liquide de la deuxième extrémité de chaque canal en direction du plateau récepteur. Un dispositif de ce type est décrit dans le document WO 98/29736. Les canaux sont formés d'un faisceau de fils capillaires rassemblés sur une tête d'impression. Ils sont commandés tous ensemble.- Means for expelling a drop of liquid from the second end of each channel towards the receiving plate. A device of this type is described in document WO 98/29736. The channels are formed by a bundle of capillary wires gathered on a print head. They are ordered all together.
Les documents US 4 058 146 et EP 0 955 084 proposent des réalisations semblables, mais l'expulsion du liquide s'effectue alors par simple contact avec le plateau récepteur. Il en est de même pour le dispositif décrit dans le document US 4 621 665 mais, dans ce cas, il n'y a pas de changement de format entre le plateau réservoir et le plateau récepteur.Documents US 4,058,146 and EP 0 955 084 propose similar embodiments, but the expulsion of the liquid is then carried out by simple contact with the receiving plate. It is the same for the device described in the document US 4,621,665 but, in this case, there is no change in format between the reservoir tray and the receiver tray.
Le dispensateur selon l'invention est conçu pour répondre, mieux que les systèmes de l'art antérieur susmentionnés, aux principales exigences suivantes:The dispenser according to the invention is designed to respond, better than the systems of the prior art mentioned above, to the following main requirements:
- homogénéité du trajet du liquide entre les deux plateaux et volume mort minimum;- homogeneity of the path of the liquid between the two plates and minimum dead volume;
- possibilité d'utiliser des plateaux réservoirs et des plateaux récepteurs de différentes dimensions; - absence de contamination du liquide traversant les canaux;- possibility of using tank trays and receiving trays of different dimensions; - absence of contamination of the liquid passing through the channels;
- homogénéité en volume des micro-gouttes.- homogeneity in volume of the micro-drops.
Pour atteindre cet objectif, le dispensateur selon l'invention est caractérisé en ce que les canaux sont formés dans une pluralité de plaques souples de façon à converger de leurs premières extrémités vers leurs deuxièmes extrémités, en ce que ces plaques sont liées ensemble par leur partie qui comporte les deuxièmes extrémités des canaux et en ce que chaque plaque est formée de deux feuilles polymériques scellées ensemble et dont l'une, au moins, est dotée d'un réseau de rainures convergentes formant les canaux.To achieve this objective, the dispenser according to the invention is characterized in that the channels are formed in a plurality of flexible plates so as to converge from their first ends to their second ends, in that these plates are linked together by their part which has the second ends of the channels and in that each plate is formed of two polymeric sheets sealed together and one of which, at least, has a network of converging grooves forming the channels.
De façon avantageuse, dispensateur selon l'invention présente encore les principales caractéristiques suivantes:Advantageously, the dispenser according to the invention also has the following main characteristics:
- le plateau réservoir est fermé, de façon étanche, par un couvercle que traversent les canaux et les moyens de remplissage sont agencés de manière à établir une surpression dans l'espace compris entre le couvercle et les cavités; - les moyens de remplissage comportent un soufflet réunissant le couvercle et son plateau par leur périphérie;- The reservoir plate is closed, in a leaktight manner, by a cover through which the channels pass and the filling means are arranged so as to establish an overpressure in the space between the cover and the cavities; - The filling means comprise a bellows joining the cover and its tray by their periphery;
- chaque canal comporte un premier rétrécissement situé à proximité de sa deuxième extrémité et un deuxième rétrécissement situé à cette extrémité et les moyens d'expulsion comportent un actionneur piézo-électrique disposé sur une paroi extérieure du canal, entre ses deux rétrécissements, et ayant pour rôle de la déformer à cet endroit de façon à réduire l'épaisseur du canal;- Each channel has a first narrowing located near its second end and a second narrowing located at this end and the expulsion means comprise a piezoelectric actuator disposed on an outer wall of the channel, between its two narrowing, and having the role of deforming it there so as to reduce the thickness of the channel;
- les moyens d'expulsion comportent un deuxième actionneur piézoélectrique identique au premier et disposé en face de lui sur l'autre paroi extérieure du canal;- The expulsion means comprise a second piezoelectric actuator identical to the first and arranged opposite it on the other outer wall of the channel;
- l'actionneur piézo-électrique est formé d'un empilement qui comporte, en partant de la paroi extérieure du canal, une électrode métallique inférieure, une couche d'isolation, une couche de matériau piézo-électrique, une nouvelle couche d'isolation et une électrode métallique supérieure; enfin,- the piezoelectric actuator is formed of a stack which comprises, starting from the outer wall of the channel, a lower metal electrode, an insulation layer, a layer of piezoelectric material, a new insulation layer and an upper metal electrode; finally,
- chaque actionneur est commandé individuellement.- each actuator is controlled individually.
D'autres caractéristiques de l'invention ressortiront de la description qui va suivre, faite en regard du dessin annexé, sur lequel:Other characteristics of the invention will emerge from the description which follows, given with reference to the appended drawing, in which:
- les figures 1 et 2 représentent, respectivement vu de face et de côté, un dispensateur selon l'invention,FIGS. 1 and 2 represent, respectively seen from the front and from the side, a dispenser according to the invention,
- la figure 3 montre, disposés côte à côte, en respectant le rapport de leurs dimensions, un plateau réservoir et un plateau récepteur;- Figure 3 shows, arranged side by side, respecting the ratio of their dimensions, a tank tray and a receiver tray;
- la figure 4 est une vue en coupe d'un canal, etFIG. 4 is a sectional view of a channel, and
- la figure 5 montre, en coupe, la structure de l'actionneur associé à chaque canal.- Figure 5 shows, in section, the structure of the actuator associated with each channel.
Les figures 1 et 2 montrent en 10 un plateau réservoir, en verre ou plastique rigide, doté d'une pluralité de cavités 12, disposées en matrice, dans chacune desquelles est disposé un liquide biologique 14 dont des échantillons doivent être déposés, sous forme de micro-gouttes, sur un plateau récepteur miniaturisé 16, également en verre ou plastique rigide (nylon).Figures 1 and 2 show at 10 a reservoir plate, made of rigid glass or plastic, provided with a plurality of cavities 12, arranged in a matrix, in each of which is disposed a biological liquid 14, samples of which must be deposited, in the form of micro-drops, on a miniaturized receiving tray 16, also made of glass or rigid plastic (nylon).
On notera immédiatement, en se référant à la figure 3 car, pour d'évidentes raisons, cela n'apparaît pas sur les figures 1 et 2, que les deux plateaux ont des dimensions très différentes. Typiquement, le plateau réservoir 10 a une surface d'environ 100 cm2 (12.5 cm x 8.5 cm) et possède 384 cavités 12, ayant un volume d'environ 100 μl, disposées en une matrice de 16 colonnes de 24 rangées et distantes les unes des autres, centre à centre, d'environ 4.5 mm. Par contre, le plateau récepteur 16 ne possède pas de cavités et a une surface d'environ seulement 1 cm2 (1.2 cm x 0.8 cm).It will be noted immediately, with reference to FIG. 3 because, for obvious reasons, this does not appear in FIGS. 1 and 2, that the two plates have very different dimensions. Typically, the reservoir tray 10 has a surface of approximately 100 cm 2 (12.5 cm x 8.5 cm) and has 384 cavities 12, having a volume of approximately 100 μl, arranged in a matrix of 16 columns of 24 rows and separated by each other, center to center, approximately 4.5 mm. By cons, the receiving plate 16 has no cavities and has an area of only about 1 cm 2 (1.2 cm x 0.8 cm).
Pour prélever du liquide contenu dans les cavités 12 et en projeter un réseau de micro-gouttes sur le plateau récepteur 16, le dispositif selon l'invention comporte une pluralité de plaques de transfert souples 18 assemblées entre elles. Ces plaques sont réalisées en polyimide, par exemple et ont une épaisseur de l'ordre de 50 à 150 μm.To take the liquid contained in the cavities 12 and project a network of micro-drops onto the receiving plate 16, the device according to the invention comprises a plurality of flexible transfer plates 18 assembled together. These plates are made of polyimide, for example and have a thickness of the order of 50 to 150 μm.
Chaque plaque 18 comporte une partie inférieure en forme de trapèze isocèle 20, formant une interface fluidique, dont la grande base a sensiblement la même longueur que la largeur du plateau réservoir 10 et est crénelée de manière à se terminer par autant de portions d'extrémités 22 que le plateau réservoir comporte de colonnes de cavités 12, soit 16 dans l'exemple décrit. Les créneaux sont dimensionnés de manière à ce que les portions 22 puissent pénétrer dans les cavités 12. L'interface fluidique 20 en forme de trapèze est prolongée, à partir de sa petite base, par une partie rectangulaire 24 dont la longueur correspond sensiblement à la largeur fe du plateau récepteur 16.Each plate 18 has a lower part in the form of an isosceles trapezoid 20, forming a fluidic interface, the large base of which has substantially the same length as the width of the reservoir plate 10 and is crenellated so as to end in as many end portions. 22 that the reservoir plate comprises columns of cavities 12, ie 16 in the example described. The slots are dimensioned so that the portions 22 can penetrate into the cavities 12. The fluidic interface 20 in the shape of a trapezoid is extended, from its small base, by a rectangular part 24 whose length corresponds substantially to the width fe of the receiving plate 16.
Chaque plaque souple 18 est dotée d'un faisceau de canaux 26 qui prennent naissance dans chacune de ses portions d'extrémités 22 et se terminent, parallèlement les uns aux autres, dans la partie supérieure 24. Typiquement, dans l'exemple de réalisation décrit, les canaux 26 sont alors distants, les uns des autres, centre à centre, de 0.5 mm.Each flexible plate 18 is provided with a bundle of channels 26 which originate in each of its end portions 22 and terminate, parallel to each other, in the upper part 24. Typically, in the embodiment described , the channels 26 are then spaced from each other, center to center, by 0.5 mm.
Le dispositif selon l'invention comporte autant de plaques identiques 18 que le plateau réservoir 10 comporte de rangées, soit 24 dans l'exemple décrit, les portions d'extrémités 22 de chaque plaque étant destinées à prendre place dans l'une des colonnes du plateau.The device according to the invention comprises as many identical plates 18 as the reservoir plate 10 comprises rows, that is 24 in the example described, the end portions 22 of each plate being intended to take place in one of the columns of the tray.
Les plaques souples 18 sont rassemblées, à leur partie supérieure, parallèlement les unes aux autres, dans un cadre 28, pour former une tête d'impression dont la longueur correspond sensiblement à la longueur L2 du plateau récepteur 16 et dont la largeur, comme déjà mentionné, correspond sensiblement à sa largeur fe.The flexible plates 18 are assembled, at their upper part, parallel to each other, in a frame 28, to form a printing head whose length corresponds substantially to the length L2 of the receiver plate 16 and whose width, as already mentioned, corresponds substantially to its width fe.
Il va de soi que les plaques pourraient aussi avoir une base de longueur correspondant à la longueur L1 du plateau réservoir 10. Ainsi que le montrent les figures 1 et 2, le plateau réservoir 10 est fermé, de manière étanche, par un couvercle 30 traversé, également de manière étanche, par les plaques souples 18. L'étanchéité sur la périphérie est assurée par un soufflet 32 dont le rôle apparaîtra plus loin.It goes without saying that the plates could also have a base of length corresponding to the length L1 of the reservoir tray 10. As shown in FIGS. 1 and 2, the reservoir tray 10 is closed, in a leaktight manner, by a cover 30 traversed , also in a sealed manner, by the flexible plates 18. The sealing on the periphery is ensured by a bellows 32 whose role will appear below.
On se référera maintenant à la figure 4 qui montre, à plus grande échelle, la façon dont sont réalisées les plaques souples 18 et leurs canaux 26. Il apparaît que ces plaques sont formées de deux minces feuilles de plastique 34 et 36 dont l'une, la feuille supérieure 34 sur la figure, a été préalablement gravée, par tout procédé bien connu de l'homme de métier, pour dessiner le contour des canaux 26 et qui sont ensuite assemblées l'une à l'autre par un procédé de laminage, également bien connu de l'homme de métier.We will now refer to FIG. 4 which shows, on a larger scale, the way in which the flexible plates 18 and their channels 26 are made. It appears that these plates are formed from two thin plastic sheets 34 and 36, one of which , the upper sheet 34 in the figure, was previously engraved, by any process well known to those skilled in the art, to draw the outline of the channels 26 and which are then assembled to each other by a rolling process , also well known to those skilled in the art.
Typiquement, les feuilles 34 et 36 ont une épaisseur de 25 à 50 μm, alors que les canaux 26 ont une profondeur de 70 à 50 μm et une largeur de 30 à 1000 μm. Le volume total d'un canal est d'environ 0.5 à 3 μL.Typically, the sheets 34 and 36 have a thickness of 25 to 50 μm, while the channels 26 have a depth of 70 to 50 μm and a width of 30 to 1000 μm. The total volume of a channel is approximately 0.5 to 3 μL.
Dans leur partie rectangulaire 24, les plaques 18 comportent, fixé sur leur feuille supérieure 34, en face de chaque canal 26, un actionneur piézoélectrique 38 ayant pour rôle de déformer la feuille à cet endroit afin de réduire l'épaisseur du canal.In their rectangular part 24, the plates 18 comprise, fixed on their upper sheet 34, opposite each channel 26, a piezoelectric actuator 38 whose role is to deform the sheet at this location in order to reduce the thickness of the channel.
Au-dessus de l'actionneur 38,- le canal 26 débouche à l'extérieur de la feuille par un rétrécissement formant bec 40, tandis que, de l'autre côté, le canal présente un rétrécissement 42. Dans l'exemple décrit, le bec 40 et le rétrécissement 42 ont la même profondeur, de 10 à 40 μm, et la même largeur, de 40 à 90 μm. Les dimensions du rétrécissement peuvent même être inférieures à celles du bec. La figure 5 montre que l'actionneur 38 est formé d'un empilement qui comporte, en partant de la feuille 34, une électrode métallique inférieure 44, une couche d'isolation 46, une couche de matériau piézo-électrique 48, une nouvelle couche d'isolation 50 et une électrode métallique supérieure 52. Les deux électrodes sont associées à des conducteurs électriques 54 permettant la commande de l'actionneur.Above the actuator 38, the channel 26 opens to the outside of the sheet by a narrowing forming a spout 40, while, on the other side, the channel has a narrowing 42. In the example described, the spout 40 and the narrowing 42 have the same depth, from 10 to 40 μm, and the same width, from 40 to 90 μm. The dimensions of the narrowing may even be smaller than those of the spout. FIG. 5 shows that the actuator 38 is formed of a stack which comprises, starting from the sheet 34, a lower metal electrode 44, an insulation layer 46, a layer of piezoelectric material 48, a new layer insulation 50 and an upper metal electrode 52. The two electrodes are associated with electrical conductors 54 allowing the actuator to be controlled.
Les électrodes 44 et 52 sont déposées par évaporation, tandis que les couches d'isolation 46 et 50 sont déposées par plasma et la couche piézoélectrique 48 est déposée par vaporisation à l'aide d'un magnétron. Comme représenté sur la figure 1, les conducteurs électriques d'alimentation des différents actionneurs 38 aboutissent à un circuit de commande 56 qui, sous les ordres d'un ordinateur 58, assure leur excitation.The electrodes 44 and 52 are deposited by evaporation, while the insulation layers 46 and 50 are deposited by plasma and the piezoelectric layer 48 is deposited by vaporization using a magnetron. As shown in FIG. 1, the electrical supply conductors of the various actuators 38 lead to a control circuit 56 which, under the orders of a computer 58, ensures their excitation.
En fonctionnement, l'ensemble formé par les plaques de transfert 18 assemblées est placé au-dessus du plateau réservoir 10 dont les cavités 12 contiennent les liquides 14 à transférer sur le plateau récepteur 16. L'alignement est réalisé de manière à ce qu'après avoir traversé le couvercle 30, chacune des portions d'extrémités 22 des plaques de transfert 18 se trouve à la verticale d'une cavité 12. Lorsque les extrémités des plaques sont immergées dans le liquide, celui-ci est aspiré dans les différents canaux 26 par capillarité.In operation, the assembly formed by the transfer plates 18 assembled is placed above the reservoir plate 10, the cavities 12 of which contain the liquids 14 to be transferred to the receiver plate 16. The alignment is carried out so that after passing through the cover 30, each of the end portions 22 of the transfer plates 18 is located vertically in a cavity 12. When the ends of the plates are immersed in the liquid, the latter is sucked into the different channels 26 by capillarity.
Il est nécessaire ensuite d'appuyer sur le couvercle 30 pour comprimer le soufflet 32 afin d'établir dans l'enceinte une surpression de quelques millibars, dont la valeur est lue sur un manomètre 60. Du fait de cette surpression, le liquide continue sa montée dans les canaux 26, traverse les rétrécissements 42 et se trouve stoppé au niveau des becs 40 par l'effet de tension de surface.It is then necessary to press on the cover 30 to compress the bellows 32 in order to establish in the enclosure an overpressure of a few millibars, the value of which is read on a pressure gauge 60. Due to this overpressure, the liquid continues its mounted in the channels 26, passes through the constrictions 42 and is stopped at the level of the spouts 40 by the effect of surface tension.
Pour éjecter le liquide en direction du plateau récepteur 16, il suffit alors de donner l'ordre à l'ordinateur 58 d'appliquer aux bornes des électrodes 44 et 52 de chaque actionneur 38 une impulsion électrique qui provoque un rétrécissement du canal 26 correspondant. Une partie du liquide qui s'y trouve, empêchée de revenir en arrière par le rétrécissement" 42, est ainsi éjectée par le bec 40 et projetée sur le plateau récepteur 16, à un endroit bien déterminé.To eject the liquid in the direction of the receiving plate 16, it then suffices to give the order to the computer 58 to apply across the electrodes 44 and 52 of each actuator 38 an electric pulse which causes a narrowing of the corresponding channel 26. A part of the liquid which is there, prevented from going back by the narrowing " 42, is thus ejected by the spout 40 and projected onto the receiving plate 16, at a well-determined location.
Le plateau récepteur 16 peut ainsi recevoir un réseau de micro-gouttes de liquide formé du même nombre de rangées et de colonnes que le plateau réservoir mais, comme déjà mentionné, à une échelle fortement réduite. Typiquement, dans l'exemple décrit, les micro-gouttes peuvent avoir un volume de 20 pL à 1 nL.The receiving plate 16 can thus receive a network of micro-drops of liquid formed of the same number of rows and columns as the reservoir plate but, as already mentioned, on a greatly reduced scale. Typically, in the example described, the micro-drops can have a volume of 20 pL to 1 nL.
Les plaques 18 contenant un volume de liquide largement supérieur à celui des micro-gouttes éjectées, plusieurs plateaux récepteurs 16 peuvent être ensuite utilisés à la suite les uns des autres.The plates 18 containing a volume of liquid much greater than that of the ejected microdrops, several receiving plates 16 can then be used one after the other.
Dans une variante de réalisation non représentée, les canaux 26 pourraient être soumis à l'effet de deux actionneurs identiques 38 disposés face à face à l'extérieur de chacune des feuilles formant les plaques souples. Une telle disposition permet de mieux maîtriser la direction d'éjection des gouttes. La présente description a été faite en se référant à une plaque souple formée de deux feuilles scellées ensemble. En variante, la plaque pourrait être formée de trois feuilles, dont la feuille centrale serait percée d'ouvertures traversantes formant les canaux.In an alternative embodiment not shown, the channels 26 could be subjected to the effect of two identical actuators 38 arranged face to face on the outside of each of the sheets forming the flexible plates. Such an arrangement allows better control of the direction of ejection of the drops. The present description has been made with reference to a flexible plate formed from two sheets sealed together. Alternatively, the plate could be formed from three sheets, the central sheet of which would be pierced with through openings forming the channels.
Ainsi est réalisé un dispensateur de liquide qui présente les principaux avantages suivants:Thus a liquid dispenser is produced which has the following main advantages:
- du fait que la tête d'impression 24 et l'interface fluidique 20 sont réunies une seule pièce, les plaques 18, le trajet du liquide est parfaitement homogène et il ne subsiste qu'un volume mort minimum ; - du fait que les plaques 18 sont souples, l'adaptation à des plateaux réservoirs 10 et des plateaux récepteurs 16 de différentes dimensions est facilitée;- the fact that the print head 24 and the fluid interface 20 are united in one piece, the plates 18, the path of the liquid is perfectly homogeneous and only a minimum dead volume remains; - the fact that the plates 18 are flexible, adaptation to reservoir plates 10 and receiving plates 16 of different dimensions is facilitated;
- du fait que les plaques souple 18 sont formées de deux feuilles polymériques assemblées par laminage et non collées, toute contamination par la colle des liquides traversant les canaux est éliminée; du fait que chaque canal 26 peut être commandé individuellement par une impulsion qui éjecte une seule micro-goutte, l'homogénéité en volume des micro-gouttes peut être assurée. - the fact that the flexible plates 18 are formed from two polymeric sheets assembled by rolling and not glued, all glue contamination of liquids passing through the channels is eliminated; since each channel 26 can be controlled individually by a pulse which ejects a single micro-drop, the volume homogeneity of the micro-drops can be ensured.

Claims

REVENDICATIONS
1. Dispensateur de fluide multi-canal permettant de prélever du liquide (14) dans une pluralité de cavités (12) ménagées sur un plateau réservoir (10) et de le projeter sur un plateau récepteur (16), comportant: - une pluralité de canaux souples (26) disposés en un faisceau convergent, dont les premières extrémités sont destinées à être plongées dans lesdites cavités et dont les deuxièmes extrémités sont assemblées en un réseau miniaturisé,1. Multi-channel fluid dispenser making it possible to take liquid (14) from a plurality of cavities (12) formed on a reservoir plate (10) and to project it onto a receiving plate (16), comprising: - a plurality of flexible channels (26) arranged in a convergent bundle, the first ends of which are intended to be immersed in said cavities and the second ends of which are assembled in a miniaturized network,
- des moyens de remplissage desdits canaux, à partir de leurs premières extrémités, par le liquide contenu dans les cavités, etmeans for filling said channels, from their first ends, with the liquid contained in the cavities, and
- des moyens d'expulsion d'une goutte de liquide de la deuxième extrémité de chaque canal en direction du plateau récepteur, caractérisé en ce que lesdits canaux sont formés dans une pluralité de plaques souples (18) de façon à converger de leurs premières extrémités vers leurs deuxièmes extrémités, en ce que lesdites plaques (18) sont liées ensemble par leur partie (24) qui comporte les deuxièmes extrémités des canaux et en ce que chaque plaque est formée de deux feuilles polymériques (34, 36) scellées ensemble et dont l'une, au moins, est dotée d'un réseau de rainures convergentes formant lesdits canaux. - means for expelling a drop of liquid from the second end of each channel in the direction of the receiving plate, characterized in that said channels are formed in a plurality of flexible plates (18) so as to converge from their first ends towards their second ends, in that said plates (18) are linked together by their part (24) which comprises the second ends of the channels and in that each plate is formed from two polymeric sheets (34, 36) sealed together and of which at least one has a network of converging grooves forming said channels.
2. Dispensateur selon la revendication 1 , caractérisé en ce que le plateau réservoir (10) est fermé, de manière étanche, par un couvercle (30) que traversent les canaux et en ce que lesdits moyens de remplissage sont agencés pour établir une surpression dans l'espace compris entre le couvercle et les cavités. 2. Dispenser according to claim 1, characterized in that the reservoir plate (10) is closed, in a leaktight manner, by a cover (30) which the channels pass through and in that said filling means are arranged to establish an overpressure in the space between the cover and the cavities.
3. Dispensateur selon la revendication 2, caractérisé en ce que lesdits moyens de remplissage comportent un soufflet (32) réunissant le couvercle (30) et son plateau (10) par leur périphérie.3. Dispenser according to claim 2, characterized in that said filling means comprise a bellows (32) joining the cover (30) and its plate (10) by their periphery.
4. Dispensateur selon la revendication 1 , caractérisé en ce que chaque canal4. Dispenser according to claim 1, characterized in that each channel
(26) comporte un premier rétrécissement (42) situé à proximité de sa deuxième extrémité- et un deuxième rétrécissement (40) situé à ladite extrémité et en ce que lesdits moyens d'expulsion comportent un actionneur piézo-électrique (38) disposé sur une paroi extérieure du canal, entre ses deux rétrécissements, et ayant pour rôle de la déformer à cet endroit afin de réduire l'épaisseur du canal. (26) has a first constriction (42) located near its second end and a second constriction (40) located at said end end and in that said expulsion means comprise a piezoelectric actuator (38) disposed on an outer wall of the channel, between its two narrowing, and having the role of deforming it there in order to reduce the thickness of the channel .
5. Dispensateur selon la revendication 4, caractérisé en ce que lesdits moyens d'expulsion comportent un deuxième actionneur piézo-électrique (38) identique au premier et disposé en face de lui sur l'autre paroi extérieure du canal.5. A dispenser according to claim 4, characterized in that said expulsion means comprise a second piezoelectric actuator (38) identical to the first and arranged opposite it on the other outer wall of the channel.
6. Dispensateur selon l'une des revendications 4 et 5, caractérisé en ce que ledit actionneur est formé d'un empilement qui comporte, en partant de la paroi extérieure du canal, une électrode métallique inférieure (44), une couche d'isolation (46), une pastille de matériau piézo-électrique (48), une nouvelle couche d'isolation (50) et une électrode métallique supérieure (52). 6. Dispenser according to one of claims 4 and 5, characterized in that said actuator is formed of a stack which comprises, starting from the outer wall of the channel, a lower metal electrode (44), an insulation layer (46), a pellet of piezoelectric material (48), a new insulating layer (50) and an upper metal electrode (52).
7. Dispensateur selon l'une des revendications 4 à 6, caractérisé en ce chaque actionneur (38) est commandé individuellement. 7. Dispenser according to one of claims 4 to 6, characterized in that each actuator (38) is controlled individually.
EP02740180A 2001-07-05 2002-06-28 Multi-channel fluid dispenser Expired - Lifetime EP1401581B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP02740180A EP1401581B1 (en) 2001-07-05 2002-06-28 Multi-channel fluid dispenser

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP01810661 2001-07-05
EP01810661A EP1273346A1 (en) 2001-07-05 2001-07-05 Multi-channel fluid dispensing apparatus
PCT/CH2002/000353 WO2003004163A1 (en) 2001-07-05 2002-06-28 Multi-channel fluid dispenser
EP02740180A EP1401581B1 (en) 2001-07-05 2002-06-28 Multi-channel fluid dispenser

Publications (2)

Publication Number Publication Date
EP1401581A1 true EP1401581A1 (en) 2004-03-31
EP1401581B1 EP1401581B1 (en) 2005-03-30

Family

ID=8184007

Family Applications (2)

Application Number Title Priority Date Filing Date
EP01810661A Withdrawn EP1273346A1 (en) 2001-07-05 2001-07-05 Multi-channel fluid dispensing apparatus
EP02740180A Expired - Lifetime EP1401581B1 (en) 2001-07-05 2002-06-28 Multi-channel fluid dispenser

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP01810661A Withdrawn EP1273346A1 (en) 2001-07-05 2001-07-05 Multi-channel fluid dispensing apparatus

Country Status (6)

Country Link
US (1) US6904945B2 (en)
EP (2) EP1273346A1 (en)
AT (1) ATE291965T1 (en)
CA (1) CA2452184A1 (en)
DE (1) DE60203507T2 (en)
WO (1) WO2003004163A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7958887B2 (en) * 2006-03-10 2011-06-14 Aradigm Corporation Nozzle pore configuration for intrapulmonary delivery of aerosolized formulations
DE102008022835B3 (en) * 2008-05-12 2009-10-22 Torsten Dr. Matthias analyzer
US8352089B2 (en) * 2010-03-31 2013-01-08 Fishman Corporation Remotely controlled fluid dispenser
EP2771128A4 (en) * 2011-10-28 2015-09-30 Hewlett Packard Development Co Parallel addressing method

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4058146A (en) * 1975-07-11 1977-11-15 Dynatech Laboratories Incorporated Method and apparatus for transferring liquid
DE3410508C2 (en) * 1984-03-22 1986-06-26 Kernforschungsanlage Jülich GmbH, 5170 Jülich Serial filling device for filling the cups of a micro cup plate
EP0615470B1 (en) * 1991-12-04 1995-12-13 The Technology Partnership Public Limited Company Fluid droplet production apparatus and method
GB9225098D0 (en) * 1992-12-01 1993-01-20 Coffee Ronald A Charged droplet spray mixer
JP2974537B2 (en) * 1993-04-07 1999-11-10 株式会社日立製作所 Capillary array, electrophoresis method and electrophoresis apparatus
CA2276462C (en) * 1996-12-31 2007-06-12 Genometrix Incorporated Multiplexed molecular analysis system apparatus and method
EP0955084B1 (en) * 1998-04-27 2006-07-26 Corning Incorporated Method of depositing an array of biological samples using a redrawn capillary reservoir

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03004163A1 *

Also Published As

Publication number Publication date
US20040238064A1 (en) 2004-12-02
WO2003004163A1 (en) 2003-01-16
DE60203507D1 (en) 2005-05-04
CA2452184A1 (en) 2003-01-16
US6904945B2 (en) 2005-06-14
DE60203507T2 (en) 2006-02-09
ATE291965T1 (en) 2005-04-15
EP1273346A1 (en) 2003-01-08
EP1401581B1 (en) 2005-03-30

Similar Documents

Publication Publication Date Title
EP1100729B1 (en) Fluid product sample
EP1827694B1 (en) Drop dispenser device
FR2691404A1 (en) Multi-layer electrothermal ink print head.
EP1672394B1 (en) Method for producing a device having a plastic membrane and device so manufactured
EP0014918A1 (en) Apparatus for depositing ink droplets on a recording medium
EP2318136A1 (en) Method and device for manipulating and observing liquid droplets
WO2019215417A1 (en) Reservoir for liquid, carousel for such reservoirs, and distribution device
WO2017042115A1 (en) Liquid sample support substrate, assembly comprising such a substrate and use thereof
WO2001049422A1 (en) Device for collectively filling blind cavities
EP1401581B1 (en) Multi-channel fluid dispenser
EP3183046A1 (en) Distribution device comprising a distributor with polygonal channels and contacting assembly comprising such a distribution device
WO2008037505A1 (en) Process and device for manufacturing individual packaging for a liquid or solid product at a very high production rate
WO2007066000A1 (en) Colour display device
FR2811588A1 (en) HEAT INJECTION AND DOSING HEAD, MANUFACTURING METHOD THEREOF, AND FUNCTIONALIZATION OR ADDRESSING SYSTEM COMPRISING THE SAME
EP1830694A2 (en) Method for making a miniaturized device in volume
WO2012117182A2 (en) Process for monolithic series connection of the photovoltaic cells of a solar module and a photovoltaic module implementing this process
EP2942111B1 (en) Device for producing a deposit of particles on a substrate and depositing method using such a device
EP3112793A1 (en) Device for dispensing falling film on a plate cooler comprising first and second distribution stages
FR2974739A1 (en) SOLID REACTOR MODULE / HEAT PUMP COMPRISING GAS DIFFUSERS WITH REDUCED SHUTDOWN HAZARDS
WO2004001493A1 (en) Method for production of a device defining a volume for retaining a fluid or a sensitive material
FR2676023A1 (en) MODULAR MULTIJET DEFLECTION HEAD AND METHOD OF MANUFACTURE.
FR3139738A1 (en) Method for simultaneously depositing several different conductive inks adjacently on the same substrate
FR2795135A1 (en) Micro-propulsion system for satellite includes reservoir in substrate with orifice and electrical resistance for ejecting charged solid particles
EP3904019A1 (en) Head for gripping by suction with foam body
FR3088312A1 (en) Multi-channel insert device in particular for capsule or pod, or other similar article for liquid dispenser and associated method.

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

17P Request for examination filed

Effective date: 20031222

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

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 CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

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: 20050330

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: 20050330

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT;WARNING: LAPSES OF ITALIAN PATENTS WITH EFFECTIVE DATE BEFORE 2007 MAY HAVE OCCURRED AT ANY TIME BEFORE 2007. THE CORRECT EFFECTIVE DATE MAY BE DIFFERENT FROM THE ONE RECORDED.

Effective date: 20050330

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: 20050330

Ref country code: IE

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: 20050330

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: 20050330

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REF Corresponds to:

Ref document number: 60203507

Country of ref document: DE

Date of ref document: 20050504

Kind code of ref document: P

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: FRENCH

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: 20050628

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: 20050628

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: 20050630

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: 20050630

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: 20050630

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050630

REG Reference to a national code

Ref country code: CH

Ref legal event code: NV

Representative=s name: GLN GRESSET & LAESSER NEUCHATEL CABINET DE CONSEIL

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 FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20050711

GBT Gb: translation of ep patent filed (gb section 77(6)(a)/1977)

Effective date: 20050711

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

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: 20050908

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: IE

Ref legal event code: FD4D

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

26N No opposition filed

Effective date: 20060102

BERE Be: lapsed

Owner name: S.A. *SEYONIC

Effective date: 20050630

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: 20050630

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20100630

Year of fee payment: 9

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20100629

Year of fee payment: 9

Ref country code: GB

Payment date: 20100625

Year of fee payment: 9

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20110628

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

Effective date: 20120229

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120103

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110630

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 60203507

Country of ref document: DE

Effective date: 20120103

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110628

REG Reference to a national code

Ref country code: CH

Ref legal event code: PFA

Owner name: SEYONIC SA, CH

Free format text: FORMER OWNER: SEYONIC SA, CH

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 20160627

Year of fee payment: 15

REG Reference to a national code

Ref country code: CH

Ref legal event code: PFA

Owner name: SEYONIC SA, CH

Free format text: FORMER OWNER: SEYONIC SA, CH

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20170630

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20170630