EP1401581B1 - Multi-channel fluid dispenser - Google Patents

Multi-channel fluid dispenser Download PDF

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Publication number
EP1401581B1
EP1401581B1 EP02740180A EP02740180A EP1401581B1 EP 1401581 B1 EP1401581 B1 EP 1401581B1 EP 02740180 A EP02740180 A EP 02740180A EP 02740180 A EP02740180 A EP 02740180A EP 1401581 B1 EP1401581 B1 EP 1401581B1
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EP
European Patent Office
Prior art keywords
duct
dispenser
ducts
cavities
channels
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EP02740180A
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German (de)
French (fr)
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EP1401581A1 (en
Inventor
Marc Boillat
Bart Van Der Schoot
Andreas Kuoni
Roeland Papen
Nico De Rooij
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Seyonic SA
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Seyonic SA
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—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 realization of miniaturized networks to high density of samples of biological substances (oligonucleotides, DNA, ...), often referred to as “biochips", for their treatment.
  • the invention relates to a multi-channel fluid dispenser for taking liquid from a plurality of cavities arranged on a reservoir tray and then depositing a network of micro-drops on a receiving tray so as to constitute a "biochip".
  • the channels are formed of a bundle of capillary threads gathered on a head printing. They are ordered together.
  • the present invention aims at providing a dispenser constituting a version improved systems of the prior art mentioned above.
  • Figures 1 and 2 show in 10 a tank tray, glass or plastic rigid, having a plurality of cavities 12, arranged in a matrix, in each of which is disposed a biological fluid 14 whose samples must to be deposited, in the form of microdrops, on a receiving tray miniaturized 16, also made of glass or rigid plastic (nylon).
  • the reservoir tray 10 has an area of about 100 cm 2 (12.5 cm x 8.5 cm) and has 384 cavities 12, having a volume of about 100 ⁇ l, arranged in a matrix of 16 columns of 24 rows and distant the each other, center to center, about 4.5 mm.
  • the receiver plate 16 has no cavities and has an area of only about 1 cm 2 (1.2 cm ⁇ 0.8 cm).
  • the device according to the invention comprises a plurality of flexible transfer plates 18 assembled between they. These plates are made of polyimide, for example, and have a thickness of the order of 50 to 150 microns.
  • Each plate 18 comprises an isosceles trapezoid-shaped lower portion 20, forming a fluidic interface, the large base of which has substantially the same length as the width I 1 of the reservoir plate 10 and is crenellated so as to end with as many portions of ends 22 that the tank plate comprises columns of cavities 12, 16 in the example described.
  • the slots are sized so that the portions 22 can enter the cavities 12.
  • the fluidic interface 20 in trapezoidal shape is extended, from its small base, by a rectangular portion 24 whose length substantially corresponds to the width I 2 of the receiving plate 16.
  • Each flexible plate 18 is provided with a bundle of channels 26 which take birth in each of its end portions 22 and end, parallel to each other, in the upper part 24. Typically, in the embodiment described, the channels 26 are then distant, each others, center to center, 0.5 mm.
  • the device according to the invention comprises as many identical plates 18 as the tank tray 10 has rows, ie 24 in the example described, the end portions 22 of each plate being intended to take place in one of the tray's columns.
  • the flexible plates 18 are gathered, at their upper part, parallel to each other, in a frame 28, to form a print head whose length substantially corresponds to the length L 2 of the receiving plate 16 and whose width, as already mentioned, corresponds substantially to its width I 2 .
  • the plates could also have a base of length corresponding to the length L1 of the tank plate 10.
  • the reservoir plate 10 is closed, sealingly, by a cover 30 crossed, also so sealed, by the flexible plates 18.
  • the sealing on the periphery is ensured by a bellows 32 whose role will appear later.
  • FIG 4 shows, on a larger scale, the in which the flexible plates 18 and their channels 26 are made. appears that these plates are formed of two thin sheets of plastic 34 and 36, one of which, the upper sheet 34 in the figure, has been previously etched, by any method well known to those skilled in the art, to draw the contour of the channels 26 and which are then assembled to one another by a rolling method, also well known to those skilled in the art.
  • the sheets 34 and 36 have a thickness of 25 to 50 ⁇ m and the total volume of a channel is about 0.5 to 3 ⁇ L.
  • the plates 18 comprise, fixed on their upper sheet 34, opposite each channel 26, a piezoelectric actuator 38 having the role of deforming the sheet at that location in order to reduce the thickness of the channel.
  • the channel 26 opens out of the sheet by a narrowing forming 40, while, on the other side, the channel has a narrowing 42.
  • the nozzle 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 shrinkage can even be lower than those of the beak.
  • 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 insulation layer 50 and an upper metal electrode 52.
  • the two electrodes are associated with electrical conductors 54 allowing control of the actuator.
  • 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.
  • the electrical supply conductors different actuators 38 lead to a control circuit 56 which, under the command of a computer 58, ensures their excitation.
  • the assembly formed by the transfer plates 18 assembled is placed above the tank plate 10 whose cavities 12 contain the liquids 14 to be transferred to the receiving tray 16.
  • the alignment is made so that after having crossed the lid 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, it 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 plateau but, as already mentioned, on a greatly reduced scale.
  • the micro-drops may have a volume of 20 ⁇ L to 1 ⁇ L.
  • the channels 26 could to be subjected to the effect of two identical actuators 38 arranged face to face with the outside of each of the sheets forming the flexible plates. Such a provision makes it possible to better control the direction of ejection of the drops.
  • the plate could be formed of three leaves, the central leaf of which would be pierced with openings through 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

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 realization of miniaturized networks to high density of samples of biological substances (oligonucleotides, DNA, ...), often referred to as "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 oligonucleotides 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 Supplement, Vol. 21, January 1999).Such networks are particularly useful tools in the field of molecular biology, as attested in particular by the publications "High-density Oligonucleotides Arrays "(A. P. Blanchard et al. - Biosensors & Biolectronics, Vol. 11, No. 6/7, pp. 686-690, 1996) and "Array of hope" (E. S. 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".More particularly, the invention relates to a multi-channel fluid dispenser for taking liquid from a plurality of cavities arranged on a reservoir tray and then depositing a network of micro-drops on a receiving tray so as to constitute a "biochip".

Le dispensateur selon l'invention est du type comportant:

  • 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,
  • des moyens de remplissage des canaux, à partir de leurs premières extrémités, par le liquide contenu dans les cavités, et
  • des moyens d'expulsion d'une goutte de liquide de la deuxième extrémité de chaque canal en direction du plateau récepteur.
The dispenser according to the invention is of the type comprising:
  • a plurality of flexible channels arranged in a convergent beam, the first ends of which are intended to be immersed in the cavities of the reservoir tray and whose second ends are assembled in a miniaturized network,
  • means for filling the channels, from their first ends, with the liquid contained in the cavities, and
  • means for expelling a drop of liquid from the second end of each channel towards the receiving tray.

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.A device of this type is described in WO 98/29736. The channels are formed of a bundle of capillary threads gathered on a head printing. They are ordered 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 embodiments similar, but the expulsion of the liquid is then made by simple contact with the receiving tray. It is the same for the device described in US 4,621,665 but, in this case, there is no change of format between the tank tray and the receiving tray.

La présente invention vise à fournir un dispensateur constituant une version améliorée des systèmes de l'art antérieur susmentionnés.The present invention aims at providing a dispenser constituting a version improved systems of the prior art mentioned above.

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 ;
  • ces plaques sont liées ensemble par leur partie qui comporte les deuxièmes extrémités des canaux ;
  • 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,
  • chaque canal comporte un premier rétrécissement situé à proximité de sa deuxième extrémité et un deuxième rétrécissement situé à ladite extrémité ; et
  • lesdits 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 afin de réduire l'épaisseur du canal.
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;
  • these plates are linked together by their part which comprises the second ends of the channels;
  • each plate is formed of two polymer sheets sealed together and at least one of which is provided with a network of convergent grooves forming the channels,
  • each channel has a first narrowing located near its second end and a second narrowing located at said end; and
  • said expulsion means comprise a piezoelectric actuator disposed on an outer wall of the channel, between its two constrictions, and having the role of deforming it at this point in order to reduce the thickness of the channel.

De façon avantageuse, le dispensateur selon l'invention présente encore les principales caractéristiques suivantes.

  • 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.
  • Les moyens d'expulsion comportent un deuxième actionneur piézo-électrique identique au premier et disposé en face de lui sur l'autre paroi extérieure du canal.
  • 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.
  • Les moyens d'expulsion sont agencés de manière à pouvoir agir individuellement sur chaque canal.
Advantageously, the dispenser according to the invention still has the following main characteristics.
  • The reservoir plate is closed, in a sealed 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 uniting the lid and its plate by their periphery.
  • The expulsion means comprise a second piezoelectric actuator identical to the first and disposed opposite it on the other outer wall of the channel.
  • The piezoelectric actuator is formed of a stack which, starting from the outer wall of the channel, comprises a lower metal electrode, an insulation layer, a layer of piezoelectric material, a new insulation layer, and an upper metal electrode.
  • The expulsion means are arranged to be able to act individually on each channel.

D'autres caractéristiques de l'invention ressortiront de la description qui va suivre, faite en regard du dessin annexé, sur lequel:

  • les figures 1 et 2 représentent, respectivement vu de face et de côté, un dispensateur selon l'invention,
  • la figure 3 montre, disposés côte à côte, en respectant le rapport de leurs dimensions, un plateau réservoir et un plateau récepteur;
  • la figure 4 est une vue en coupe d'un canal, et
  • la figure 5 montre, en coupe, la structure de l'actionneur associé à chaque canal.
Other features of the invention will emerge from the description which follows, given with reference to the appended drawing, in which:
  • FIGS. 1 and 2 are respectively seen from the front and from the side, a dispenser according to the invention,
  • Figure 3 shows, arranged side by side, respecting the ratio of their dimensions, a reservoir tray and a receiving tray;
  • FIG. 4 is a sectional view of a channel, and
  • 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 in 10 a tank tray, glass or plastic rigid, having a plurality of cavities 12, arranged in a matrix, in each of which is disposed a biological fluid 14 whose samples must to be deposited, in the form of microdrops, on a receiving tray miniaturized 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'apparaít 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).Note immediately, with reference to Figure 3 because, for obvious reasons, it does not appear in Figures 1 and 2, that the two plates have very different dimensions. Typically, the reservoir tray 10 has an area of about 100 cm 2 (12.5 cm x 8.5 cm) and has 384 cavities 12, having a volume of about 100 μl, arranged in a matrix of 16 columns of 24 rows and distant the each other, center to center, about 4.5 mm. On the other hand, the receiver plate 16 has no cavities and has an area of only about 1 cm 2 (1.2 cm × 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 collect liquid contained in the cavities 12 and project a network of micro-drops on the receiving plate 16, the device according to the invention comprises a plurality of flexible transfer plates 18 assembled between they. These plates are made of polyimide, for example, and have a thickness of the order of 50 to 150 microns.

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 I1 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.Each plate 18 comprises an isosceles trapezoid-shaped lower portion 20, forming a fluidic interface, the large base of which has substantially the same length as the width I 1 of the reservoir plate 10 and is crenellated so as to end with as many portions of ends 22 that the tank plate comprises columns of cavities 12, 16 in the example described.

Les créneaux sont dimensionnés de manière à ce que les portions 22 puissent pénétrer dans les cavités 12.The slots are sized so that the portions 22 can enter the cavities 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 I2 du plateau récepteur 16.The fluidic interface 20 in trapezoidal shape is extended, from its small base, by a rectangular portion 24 whose length substantially corresponds to the width I 2 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 take birth in each of its end portions 22 and end, parallel to each other, in the upper part 24. Typically, in the embodiment described, the channels 26 are then distant, each others, center to center, 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 tank tray 10 has rows, ie 24 in the example described, the end portions 22 of each plate being intended to take place in one of the tray's columns.

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 I2.The flexible plates 18 are gathered, at their upper part, parallel to each other, in a frame 28, to form a print head whose length substantially corresponds to the length L 2 of the receiving plate 16 and whose width, as already mentioned, corresponds substantially to its width I 2 .

Il va de soi que les plaques pourraient aussi avoir une base de longueur correspondant à la longueur L1 du plateau réservoir 10.It goes without saying that the plates could also have a base of length corresponding to the length L1 of the tank plate 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 apparaítra plus loin.As shown in FIGS. 1 and 2, the reservoir plate 10 is closed, sealingly, by a cover 30 crossed, also so sealed, by the flexible plates 18. The sealing on the periphery is ensured by a bellows 32 whose role will appear later.

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 apparaít 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.Reference is now made to Figure 4 which shows, on a larger scale, the in which the flexible plates 18 and their channels 26 are made. appears that these plates are formed of two thin sheets of plastic 34 and 36, one of which, the upper sheet 34 in the figure, has been previously etched, by any method well known to those skilled in the art, to draw the contour of the channels 26 and which are then assembled to one another by a rolling method, also well known to those skilled in the art.

Typiquement, les feuilles 34 et 36 ont une épaisseur de 25 à 50 µm et 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 and the total volume of a channel is about 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 piézo-électrique 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 having the role of deforming the sheet at that 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.Above the actuator 38, the channel 26 opens out of the sheet by a narrowing forming 40, while, on the other side, the channel has a narrowing 42. In the example described, the nozzle 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 shrinkage can even be lower than those of the beak.

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.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 insulation layer 50 and an upper metal electrode 52. The two electrodes are associated with electrical conductors 54 allowing control of the actuator.

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 piézo-électrique 48 est déposée par vaporisation à l'aide d'un magnétron.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.

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.As shown in FIG. 1, the electrical supply conductors different actuators 38 lead to a control circuit 56 which, under the command 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 tank plate 10 whose cavities 12 contain the liquids 14 to be transferred to the receiving tray 16. The alignment is made so that after having crossed the lid 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, it 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 the lid 30 to compress the bellows 32 in order to establish in the enclosure an overpressure of a few millibars, whose value is read on a pressure gauge 60. Because of this overpressure, the liquid continues its rise in the channels 26, passes through the constrictions 42 and is stopped at the nozzles 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 towards the receiving tray 16, it is then sufficient to order the computer 58 to apply across the electrodes 44 and 52 of each actuator 38 an electrical pulse which causes a narrowing of the corresponding channel 26. Part of the liquid that is finds, prevented from going back by the narrowing 42, is thus ejected by the spout 40 and projected on the receiving plate 16, at a place well determined.

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.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 plateau but, as already mentioned, on a greatly reduced scale.

Typiquement, dans l'exemple décrit, les micro-gouttes peuvent avoir un volume de 20 pL à 1 nL.Typically, in the example described, the micro-drops may have a volume of 20 μL to 1 μL.

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 micro-droplets ejected, several trays 16 can be then used after each 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 maítriser la direction d'éjection des gouttes.In an embodiment variant not shown, the channels 26 could to be subjected to the effect of two identical actuators 38 arranged face to face with the outside of each of the sheets forming the flexible plates. Such a provision makes it possible to better control the direction of ejection of the drops.

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.This description has been made with reference to a formed flexible plate two sheets sealed together. Alternatively, the plate could be formed of three leaves, the central leaf of which would be pierced with openings through forming the channels.

Ainsi est réalisé un dispensateur de liquide qui présente les principaux avantages suivants:

  • 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;
  • 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.
Thus is realized a liquid dispenser which has the following main advantages:
  • since the printing head 24 and the fluidic interface 20 are united in one piece, the plates 18, the liquid path is perfectly homogeneous and only a minimum dead volume remains;
  • since the plates 18 are flexible, adaptation to reservoir trays 10 and receiving trays 16 of different dimensions is facilitated;
  • since the flexible plates 18 are formed of two laminated and unglued polymeric sheets, any adhesive contamination of the liquids passing through the channels is eliminated;
  • since each channel 26 can be individually controlled by a pulse which ejects a single micro-drop, the volume homogeneity of the micro-drops can be ensured.

Claims (6)

  1. A multi-duct fluid dispenser for withdrawing liquid (14) from a plurality of cavities (12) formed in a reservoir platter (10) and spraying it onto a receiving platter (16), comprising :
    a plurality of flexible ducts (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 array,
    means of filling said ducts, from their first ends, with the liquid contained in the cavities, and
    means of expelling a drop of liquid from the second end of each duct toward the receiving platter,
    characterized in that :
    said ducts (26) are formed in a plurality of flexible plates (18) so as to converge from their first ends toward their second ends ;
    said plates (18) are joined together by their part (24) that comprises the second ends of the ducts,
    each plate is formed of two polymer sheets (34, 36) sealed together and of which at least one is endowed with an array of convergent grooves forming said ducts ;
    each duct (26) has a first narrowing (42) near its second end and a second narrowing (40) at said end ; and
    said expelling means comprise a piezoelectric actuator (38) arranged on an exterior wall of the duct, between its two narrowings, and the purpose of which is to deform said wall at this point so as to reduce the thickness of the duct.
  2. The dispenser of claim 1, characterized in that the reservoir platter (10) is sealed closed by a lid (30) through which the ducts pass and in that said filling means are arranged in such a way as to raise the pressure in the space lying between the lid and the cavities.
  3. The dispenser of claim 2, characterized in that said filling means comprise a bellows (32) connecting the lid (30) and its platter (10) at their periphery.
  4. The dispenser of claim 1, characterized in that said expelling means comprise a second piezoelectric actuator (38) identical to the first one and arranged facing it on the other exterior wall of the duct.
  5. The dispenser of any of claims 1 and 4, characterized in that said actuator is formed as a stack which comprises, starting from the exterior wall of the duct, a lower metal electrode (44), an insulating layer (46), a block of piezoelectric material (48), a further insulating layer (50) and an upper metal electrode (52).
  6. The dispenser of any of claims 1, 4 and 5, characterized in that said expelling means (38) are designed in such a way as to be able to act on each duct 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
EP01810661A EP1273346A1 (en) 2001-07-05 2001-07-05 Multi-channel fluid dispensing apparatus
EP01810661 2001-07-05
EP02740180A EP1401581B1 (en) 2001-07-05 2002-06-28 Multi-channel fluid dispenser
PCT/CH2002/000353 WO2003004163A1 (en) 2001-07-05 2002-06-28 Multi-channel fluid dispenser

Publications (2)

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

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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
JP2849647B2 (en) * 1991-12-04 1999-01-20 ザ テクノロジー パートナーシップ ピーエルシー Apparatus and method for producing small droplets of fluid
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
EP2295988A2 (en) * 1996-12-31 2011-03-16 High Throughput Genomics, Inc. Multiplexed molecular analysis apparatus and its fabrication method
EP0955084B1 (en) * 1998-04-27 2006-07-26 Corning Incorporated Method of depositing an array of biological samples using a redrawn capillary reservoir

Also Published As

Publication number Publication date
US6904945B2 (en) 2005-06-14
CA2452184A1 (en) 2003-01-16
ATE291965T1 (en) 2005-04-15
EP1273346A1 (en) 2003-01-08
DE60203507D1 (en) 2005-05-04
EP1401581A1 (en) 2004-03-31
US20040238064A1 (en) 2004-12-02
WO2003004163A1 (en) 2003-01-16
DE60203507T2 (en) 2006-02-09

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