WO2003101369A2 - Dispositif de transfert de liquides - Google Patents

Dispositif de transfert de liquides Download PDF

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Publication number
WO2003101369A2
WO2003101369A2 PCT/US2003/017443 US0317443W WO03101369A2 WO 2003101369 A2 WO2003101369 A2 WO 2003101369A2 US 0317443 W US0317443 W US 0317443W WO 03101369 A2 WO03101369 A2 WO 03101369A2
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WO
WIPO (PCT)
Prior art keywords
reservoir
hquid
momentum transfer
momentum
transfer component
Prior art date
Application number
PCT/US2003/017443
Other languages
English (en)
Other versions
WO2003101369A3 (fr
Inventor
Stuart Elmes
Jonathan Pearson
Alistair Taylor
David Frank Moore
Original Assignee
Matrix Technologies Corporation
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 Matrix Technologies Corporation filed Critical Matrix Technologies Corporation
Priority to AU2003249687A priority Critical patent/AU2003249687A1/en
Publication of WO2003101369A2 publication Critical patent/WO2003101369A2/fr
Publication of WO2003101369A3 publication Critical patent/WO2003101369A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/0036—Nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/0036—Nozzles
    • B01J2219/00362—Acoustic nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • the present invention relates to a device for transferring , controlled amounts of liquid, and more particularly to a device by which controlled amounts of liquid can be simultaneously transferred to a plurality of target locations upon demand.
  • the transfer of either all or a part of the biological solution from one storage vessel to another is another useful procedure for the scientist.
  • This may, for example, take the form of transferring a few drops of a solution from a vessel with topological discontinuities to another vessel with topological discontinuities or for example from a vessel with topological discontinuities to a surface with regions of hydrophobicity or hydeophilicity which define where the dispensed drop or drops are contained.
  • FIG. 1 One known technique for transferring liquid is illustrated in Figure 1 and is described in patent WO 97/15394. It takes the concept of the microtitre plate and drills a hole into the bottom of the sample well. To cause the droplets contained within the well to be ejected, the air pressure on the surface of the liquid in the well is raised by sealing the whole top of the microtitre plate with an o-ring and cover and then applying an impulse to the cover. By pressing down onto the lid of the sample well the air above the sample contained within is compressed, this compressive wave then presses onto the liquid causing a momentum transfer which will, with sufficient over pressure, cause the liquid to be ejected from the nozzle hole in the bottom of the well.
  • the use of air as the medium of momentum transfer causes a broadening of the imparted momentum pulse width, which can have the effect of increasing the volume of liquid dispensed at the nozzle.
  • the ratio of air to liquid in the well increases and alters the momentum transfer characteristics of the system, whereby the dispensed volume will change over time.
  • sufficient air pressure may not be developed above the surface of the fluid in the other wells as a result of the air escaping out of the empty wells nozzle.
  • FIG. 2 Another known technique is illustrated in Figure 2 and is described in WO 00/24511.
  • each of the wells is individually sealed with an air tight membrane.
  • a series of pneumatic passages allows each of the wells to potentially be ejected individually although in practise they are generally fired simultaneously. With this construction, the remainder of the wells still function even if one well is empty of fluid.
  • Figure 3 is a schematic representation of the device described in patent DEI 1913076.
  • the samples are stored around the edge of the dispensing head in holes, which may be 3- 4mm in diameter, and fed to respective nozzles at the centre via micromachined channels.
  • the routing of all the microchannels is configured to achieve uniform ejection characteristics for each of the nozzles.
  • Pneumatic pressure is applied to the volume of air sitting above all of the nozzles simultaneously using a piston which drives into a flexible cover or membrane that sits above all of the nozzles.
  • a clever scheme of fast acting pneumatic valves has been employed which evacuates the air above the nozzles a timed instant after the over pressure has been applied. This allows more control over the dispensing and in theory smaller drops to be dispensed.
  • a liquid transfer system for dispensing controlled amounts of liquid upon demand, including a reservoir structure defining a plurality of reservoirs each having at least one outlet nozzle commonly provided at a lower side of the reservoir structure, a plurality of momentum transfer components each supported for vertical movement in a respective one of the plurality of reservoirs from a rest position in which a lower surface of the momentum transfer component is located within the respective reservoir facing the nozzle, and an actuator provided externally of the reservoir structure for accelerating the momentum transfer components downwards relative to the reservoir structure, so as, in use, to dispense a controlled amount of liquid through the reservoir nozzles.
  • a liquid transfer device for dispensing controlled amounts of liquid upon demand, the liquid transfer device including a reservoir structure defining a plurality of reservoirs each having at least one outlet nozzle commonly provided at a lower side of the reservoir structure, and wherein each reservoir is also provided with a momentum transfer component supported on the reservoir structure for vertical movement from a rest position in which a lower surface of the momentum transfer component is located witixin the respective reservoir facing the nozzle and an upper portion projects out of the reservoir at an upper side of the reservoir structure opposite said lower side at which said nozzles are located; the upper portion facilitating the use of an external actuator to accelerate the respective momentum transfer component downwards relative to the reservoir to dispense a controlled amount of liquid.
  • liquid transfer system or liquid transfer device for the transfer of biological materials.
  • liquid transfer system or liquid transfer device for simultaneously filling a selected number or all of an array of storage vessels with liquid, or for producing a microarray on a substrate surface.
  • a method of improving dispensing performance in a liquid transfer device that operates by relatively accelerating a momentum transfer component supported in a reservoir from a rest position towards an outlet nozzle of the reservoir, the method including reducing the distance of the momentum transfer component from the outlet nozzle in the rest position.
  • FIGS 1 to 3 illustrate known liquid transfer devices
  • Figures 4 and 5 illustrate components of a liquid transfer device according to an embodiment o£ the present invention
  • Figure 6 illustrates the assembly of a liquid transfer device according to an embodiment of the present invention
  • Figure 7 illustrates a liquid transfer device according to another embodiment of the present invention
  • Figure 8 illustrates a liquid transfer device according to another embodiment of the present invention.
  • Figure 9 illustrates an example of a construction for the momentum transfer component of the type of device shown in Figure 8.
  • FIG. 10 illustrates a liquid transfer device employing the liquid transfer device of
  • FIGs 11 to 16 illustrate examples of momentum transfer devices for use in the type of device shown in Figures 7 and 8;
  • FIGS 17 and 18 illustrate further embodiments of the present invention.
  • FIGS 19 and 20 illustrate further embodiments of the present invention.
  • FIGS 21 and 22 illustrate examples of uses of the liquid transfer device of the present invention.
  • Figures 23 and 24 illustrate further embodiments of the liquid transfer device of the present invention including features for limiting the downward movement of the momentum transfer component
  • Figure 25 illustrates a further embodiment of a liquid transfer device according to the present invention.
  • Figure 26 illustrates an embodiment of a liquid transfer system according to the present invention
  • Figure 27 explains the dimensions of an embodiment of a liquid transfer device according to the present invention.
  • Figure 28 illustrates the use of roughened momentum transfer components in an embodiment of a liquid transfer device according to the present invention
  • Figure 29 is a graph illustrating how using a momentum transfer component with a roughened surface can improve the uniformity of volume deposition
  • Figure 30 illustrates a further embodiment of a liquid transfer device according to the present invention
  • Figure 31 illustrates an example of a snap-back mechanism for use in relation to the present invention.
  • a planar reservoir structure 6 defines an ordered 2D-array of elongate cylindrical reservoirs 2 spaced at regular pitch and each having a nozzle 4 at its lower end and a relatively large opening 8 at its upper end.
  • the reservoirs are orientated parallel to each other and are of substantially identical shape.
  • the diameter of the outlet nozzle 4 is selected according to the desired size of the ejected droplets. .
  • a lid component 10 comprising a flexible membrane 12 with momentum transfer components 14 embedded into it.
  • Each momentum transfer component includes a portion 16 above the membrane and a portion 18 below the membrane, which when the lid is fitted to the reservoir structure as shown in Figure 6, has a lower surface which lies over the nozzle 4 but slightly spaced from it, as shown by the broken line in Figure 6.
  • the present invention is a passive structure, which is acted upon by an external actuation.
  • FIG. 4 and 5 The construction is shown in Figures 4 and 5 is for a 5x5 format, but the device of the present invention could be produced in other formats, such as 8 x 12 format at 9mm pitch to match those of microtitre plates.
  • the reservoirs 20 and momentum transfer components 22 are shown as circular cross-section but could, for example, also be square, triangular or other polygonal.
  • air holes are provided in the portions of the elastic membrane around the momentum transfer components to allow pressure equalisation between inside and outside the reservoirs after firing, and facilitates liquid from the bulk of the reservoir filling the space between the bottom of the momentum transfer component and the nozzle upon restoration of the momentum transfer component to the rest position in preparation for the next firing.
  • planar reservoir structure could, for example, be a microtitre plate of the kind described in W097/15394.
  • a combined storage and dispensing device according to the present invention can be produced relatively simply by building momentum transfer block structures onto a lid which is used as standard for capping microtitre plates.
  • the elastic membrane is designed taking into account the level of force that is to be used to displace the momentum transfer block. For example, it may be desired that a droplet be ejected by the force imparted by a lg mass impacting into the top part of the device at lm/s.
  • the elastic membrane is preferably made not too flexible, in order to avoid an undesirable level of smearing out of the response of the input impulse.
  • the maximum speed at which successive drops can be ejected is decided by the design of the momentum transfer column and associated supporting elastic membrane.
  • the momentum transfer column can be designed to ensure that the "on" force is applied as a sharp impulse to the fluid.
  • the "off force is controlled by the speed at which the system returns to its initial state.
  • the momentum transfer column is also designed taldng into account the level of force that is to be used to displace it. In general, the smaller the area of the lower face of the momentum transfer component compared to the nozzle diameter the less efficient the transfer of the momentum impulse into the fluid that is required to eject a droplet.
  • the dimensions are selected such that a droplet can be ejected by the application of an impulse that is less than the maximum breaking stress of the device material.
  • the diameter of the momentum transfer component bottom should generally be greater than 0.1mm.
  • the distance of the bottom of momentum transfer component from the nozzle orifice is also selected according to the degree of pressure desired to eject a droplet. Generally, the greater the distance between the bottom of the momentum transfer component and the nozzle the higher the applied impulse required to eject a droplet. Generally, the distance between the bottom of the momentum transfer component and the nozzle plate should be in the range of l ⁇ m - 2000 ⁇ m. Relatively small spacings may be achieved using relatively precise mi ⁇ omachining techniques to manufacture the device.
  • the momentum transfer component is designed such that the diameter of the portion below the elastic membrane increases along its length towards its bottom. Such a design can help to prevent the stiffness of the device becoming excessively great whilst making it easier for a given momentum impulse to build up sufficient pressure to cause ejection of a droplet.
  • Example 1 For a device compliant with 96 well microtitre plate consumables Supporting membrane thickness (a) of 300 microns.
  • a gap distance (c) between the bottom of the piston and the nozzle of 500 microns.
  • Example 2 Also for a device compliant with 96 well microtitre plate consumables
  • Example 3 For a device complaint with 384 well microtitre plate consumables:
  • Example 4 Also For a device complaint with 384 well microtitre plate consumables:
  • a reservoir depth of 5mm It has been found that the uniformity of volume deposition with variations in the amount of liquid in the reservoir can be improved by using momentum transfer components with roughened surfaces as schematically shown in Figure 28.
  • a rapid prototyping process of the kind described later was used to manufacture momentum transfer components with surface roughnesses of (a) 300 microns, (b) 600 microns and (c) 900 microns. It was found that a surface roughness of 300 microns best reduced the effect of the fluid fill height on the deposition volume.
  • the improved performance is shown by the graph of Figure 29 in comparison with a momentum transfer component having a smooth surface.
  • the test fluid used for the comparison was 1.5M Betaine monohydrate.
  • Example 5 For a device complaint with 384 well microtitre plate consumables:
  • Height of lower reservoir portion (h) is 3mm.
  • Height of upper reservoir portion (g) is 3mm.
  • a reservoir depth (e) of 6mm can, for example, be used to facilitate refilling of the reservoirs with liquid.
  • One way of doing this is to construct the device such that the lid component including the elastic membrane and momentum transfer components is removable from the reservoir structure base (e.g. microtitre plate).
  • each momentum transfer component with a through hole extending from the upper end to a side wall to allow the reservoir to be filled via such through hole.
  • this is achieved by providing the momentum transfer component as a tube-shaped structure closed at its lower end (to provide a momentum transfer surface above the nozzle) but open at its upper end and having " one or more holes (slots) formed in the side wall of the tube.
  • This "hollow" construction has the advantage of more fully exploiting the available space for liquid storage, which increases in importance the smaller the pitch between reservoirs.
  • additional air holes provided in the elastic membrane, as shown in Figure 8 facilitate the filling of the reservoir with liquid, by allowing air to escape
  • FIGS 9 to 16 illustrate examples of alternative designs for the momentum transfer component and associated elastic membrane.
  • Figure 9 illustrates an example of a construction for the momentum transfer component shown in Figure 8.
  • the device is tube-shaped, closed at its lower end and open at its upper end and including two slots 30 arranged opposite to each other in the side wall.
  • the portion of the elastic membrane covering the reservoir opening is also shown, and includes two air holes 32.
  • Figure 10 shows how these momentum transfer components are fitted into the respective reservoirs.
  • the elastic membrane is not shown.
  • Figure 11 illustrates an example of a momentum transfer component that is similar to that of Figure 9 but is of square section. The air holes in the membrane are not shown.
  • Figure 12 illustrates an example of a momentum transfer component similar to that of Figure 9 except that it includes four fluid exit slots in the tube side wall rather than two. Again, the air holes in the membrane are not shown.
  • Figure 13 illustrates another example of a momentum transfer component.
  • the device includes a solid cyhndrical body with upper and lower portions 16, 18 about a porous elastic membrane 12.
  • the porosity of the plate allows liquid in, air out and decreases the stiffness of the elastic membrane.
  • Figures 14 and 15 show perspective and side views of another example of a momentum transfer component similar to that of Figure 9 except that the upper portion 16 above the elastic membrane 12 is of greater diameter than the lower portion 18 (both portions are of smaller diameter than that of the reservoir). The air holes in the membrane are not shown.
  • FIG 16 illustrates another embodiment of the present invention, in which the momentum transfer component (which may be of solid or hollow construction) is supported on a membrane which has a weak link 40 manufactured into it which extends 360 degrees and which acts like a hinge allowing more flexibility in an otherwise relatively stiff structure. Air holes in the membrane 12 are not shown.
  • the momentum transfer component is supported by an elastic membrane at the top of the planar reservoir structure 2. However, it may also be supported elastically for vertical movement at one or more locations below the top of the planar reservoir structure.
  • Figure 17(a) and Figure 17(b) shows a horizontal cross-section.
  • the momentum transfer component includes a solid column 50 that is elastically supported in the reservoir by two sets of three spokes 52 which are secured to the side walls of the reservoir.
  • the additional bottom set of spokes increases the stability of the structure.
  • Figures 18(a) and 18(b) illustrate a variation of the design shown in Figure 17 but with 2 sets of 2 spokes. This type of construction may be produced by forming the hub 50 and spokes 52 as an integral part of the reservoir structure.
  • FIG. 19(a), Figures 19 (b) and 19(c) which are horizontal cross sections at different levels
  • Figure 20 show a cyhndrical unit cell, a plurality of which are integrally combined together in the final device.
  • Each reservoir of the planar reservoir structure 58 includes a main reservoir 60 in which the momentum transfer component 62 is located above the nozzle (not shown) and a separate fluid channel 64 that is only connected to the main reservoir 60 at a lower portion thereof.
  • the momentum transfer component 62 is elastically supported within the main reservoir 60 by an elastic membrane 66 secured to the top side of the planar reservoir structure, and which has air holes through to the main reservoir and a hole for accessing the fluid channel 64.
  • This design allows fluid to be injected at the base of the momentum transfer component minimising the risk that air becomes trapped between the bottom of the momentum transfer column and the nozzle (not shown) at the bottom of the main reservoir.
  • Prototypes of the above-described devices have been made using conventional rapid prototyping techniques such as selective laser sintering (SLS) and stereolithography. Both these techniques have yielded working devices at low cost. It is envisaged that the device could be mass-produced using injection moulding.
  • a two part (or multi-part) manufacturing process can be used.
  • a first part could define the array of reservoirs including the nozzles, and a second part the lid including the momentum transfer components.
  • These two parts can then either be bonded together or interlocked using snap fit components, which have been designed into the two parts structures.
  • the nozzle holes could depending on their required size and hence manufacturing resolution, be made in a one-part moulding process as an integral part of the reservoir structure, or formed in a subsequent process using a technique such as, for example, lithography, laser machining or ultrasonic drilling.
  • the device would be contained on a robot that would retrieve the device from a refrigerated storage area either on or off the machine in some modular structure. After removing any casing that could be used for either physical or environmental protection during storage the destination plate would be brought underneath the dispensing plate.
  • a tool could be used, which is a series of (for the 96 well device) 96 Hghtweight pins positioned in a free-floating 2D grid. It is used to impact the momentum transfer components to eject fluid from the nozzles.
  • the pin tool is rapidly brought down into contact with the tops of the momentum transfer components. Any variations in the heights of the momentum transfer components are accounted for by the free-floating nature of the pins in the pin tool.
  • the force it generates as it strikes the dispensing head is sufficient to eject fluid from the dispensing head into all the respective wells on the empty microtitre plate. Ejection volumes depend on the velocity and mass of the individual pins, the size of the nozzle and the geometry of the momentum transfer component and associated device.
  • the devices could, for example, be designed for the storage of liquid over a relatively long period of time.
  • the device is used to dispense the required reagents and then the liquid removed from the reservoirs using centrifugation or pipetting.
  • the device could then be either cleaned and re-used, or disposed of, in which case it is preferably of a design that can be manufactured at low cost.
  • the devices also have use in the preparation of microarrays of biological material, such as DNA, on, for example, a microscope slide as illustrated in Figure 22.
  • a subsection of the reservoirs could be actuated using a pin tool array as discussed above with the number and distribution of pins matching the configuration of the desired array.
  • the device could also be used in the preparation of subsets of existing Hbraries of samples.
  • individual reservoirs can be actuated using an individual pin or a user definable array pattern of pins to selectively eject reagent into/onto the required substrate.
  • the above-described devices can give sharp and consistent momentum pulses (which allows droplets of consistently relatively small size to be dispensed) for the dispensing of a relatively large number of droplets of liquid from a single reservoir because the momentum of the momentum transfer component is applied directly to the liquid (rather than via a cushion of air) even when the reservoir becomes almost emptied of its liquid content. Furthermore, since the momentum transfer component includes a portion that extends out of the upper end of the reservoir (opposite to that at which the nozzle is formed), the actuation mechanism can be external to the liquid transfer device and yet maintain the in-line aspect of the design.
  • the gap between the wall of the reservoir and the momentum transfer component is substantially the same along the entire length of the portion of the momentum transfer component that resides in the reservoir, and/or the reservoir and momentum transfer components are both cyhndrical and arranged concentrically.
  • the ejected volume depends on several factors, one of which is the stiffness of the supporting membrane. Tolerances during the manufacturing process may result in variations in the stiffness of the membrane from batch to batch and/or between individual momentum transfer components from a common batch.
  • the device is designed so that momentum transfer component is sufficiently close to the nozzle plate in the rest position so that upon the required actuation level the two parts touch thereby limiting the downward movement of the device and compensating for any variations in the stiffness of the supporting membrane.
  • a plurality of standoffs 70 are manufactured on the lower reservoir wall 72 so as to project upwards into the reservoir towards the momentum transfer component.
  • a plurality of standoffs 74 are provided on the lower portion of the momentum transfer component so as to project from the momentum transfer component towards a portion of the lower reservoir wall defining the outlet nozzle.
  • the momentum transfer components can be accelerated downwards relative to the reservoir towards the outlet nozzles by either holding the reservoir structure stationary and displacing the momentum transfer component downwards or by holding the momentum transfer component stationary and displacing the nozzle plate upwards.
  • each momentum transfer component is provided as a discrete component that can be inserted into and withdrawn from the respective reservoir separately from the other momentu transfer components.
  • the momentum transfer components are provided as individual caps 80 that can be inserted, by for example using a robot, into the individual reservoirs after they have been filled with liquid.
  • Each cyhndrical momentum transfer component is provided with an elastic supporting member 82 that rests on top of the reservoir structure when the momentum transfer component is inserted into the respective reservoir with its lower surface facing the outlet nozzle in the rest position. The elastic supporting member thus assists the setting of the respective momentum transfer component in the rest position ready for actuation and also serves to automatically return the momentum transfer component back to the rest position after each actuation.
  • a preferred actuator includes plungers for impacting against the tops of the momentum transfer components, stepper motors for repeatedly driving the plungers down into impact with the momentum transfer component, and a snap-back mechanism to avoid any plunger delivering multiple impulses to the respective momentum transfer component upon a single actuation.
  • An example of a snap-back mechanism is illustrated schematically in Figure 31.
  • the plunger 100 is driven down with an associated lever spring system 106 by the stepper motor (not shown) at a constant speed towards the top of the momentum transfer component 102, giving the desired impact force.
  • the plunger is pushed upwards relative to the lever spring system 106, and the end of the lever 103 is pushed over the lip 104 on the plunger (by virtue of the circular surface at the end of the lever 103) and towards the sloping ramp, 105 (as seen in B).
  • the lever-spring system, 106 couples with the ramp and rapidly pulls the plunger away from the surface (as seen in C). In this way, any vibrations of the plunger after this point will not affect drop ejection in anyway.
  • the actuator is set up such that the stepper motor reaches its cruise velocity before impact of the plunger with the momentum transfer component, and then decelerates sometime after the impact whereby the impact will always be consistent. It was also found that once a critical velocity was reached drops would start ejecting, but increasing the speed further appeared to have little effect on the drop size.
  • the momentum transfer components are not supported by the reservoir structure, but it is the actuator that supports the momentum transfer components in the rest position as well as providing the force for the acceleration the momentum transfer components when a droplet is to be dispensed from the respective reservoir.
  • the actuator also functions to return the momentum transfer component back to the rest position after each actuation.
  • the momentum transfer components are removably supported by the actuator, thereby facilitating replacement of the momentum transfer components.
  • the ' momentum transfer components are designed to be disposable or readily cleanable after each use to prevent contamination when a reservoir is emptied and filled with a new different hquid or when the same momentum transfer component is used for dispensing a different Hquid from a different reservoir.
  • each momentum transfer component 86 is made of two parts, a first part 88 that is not intended to come into contact with the fluid in the reservoirs and which is permanently supported by the actuator 84, and a second lower part 90 that is readily detachable from the first part and made, of a low cost material, such as for example injection moulded plastic part.
  • the lower part which is immersed in the Hquid, can be disposed of after it has been used to dispense fluid out of the Hquid reservoir through the methods outlined previously.
  • the momentum transfer component is designed with respect to the reservoir such that the space between the lower surface of the momentum transfer component and the outlet nozzle is in fluid communication with a part of the reservoir above the lower surface of the momentum transfer component. After each actuation, the space between the lower surface of the momentum transfer component and the outlet nozzle is automatically filled with fluid from the bulk of the reservoir as the momentum transfer component returns to the rest position in preparation for the next actuation.
  • This replenishing action is facihtated by the top of reservoir being open for pressure equahsation with the outside, in some cases by the use of air holes or perforations in the elastic membrane supporting the momentum transfer component on the reservoir structure.
  • a controUed amount of fluid is dispensed by displacing the momentum transfer component down towards the outlet nozzle at a rate sufficient to propagate acoustic waves and cause a directional pressure front in the fluid that is sufficiently high to cause a droplet to be ejected from the outlet nozzle.
  • the above-described devices and systems are adapted to dehver a volume of Hquid less than 1 milHHtre per reservoir and per actuation.
  • the devices can be adapted to dehver amounts of Hquid less than 1 nanohtre (i.e. in the picoHtre range).
  • the devices would typicaUy be adapted to deHver 100 to 2000 picoHtres per actuation per reservoir.

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  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

La présente invention concerne un système de transfert de liquides. Ledit système permet de distribuer des quantités contrôlées de liquide, à la demande. Le système de transfert de liquides comprend, selon un mode de réalisation, une structure de réservoir définissant une pluralité de réservoirs, chacun présentant au moins une buse de sortie généralement située sur une face inférieure de la structure de réservoir, une pluralité d'éléments de transfert de quantité de mouvement, chacun étant monté de façon à pouvoir se déplacer verticalement dans un réservoir respectif de la pluralité de réservoirs par rapport à une position de repos dans laquelle une surface inférieure de l'élément de transfert de quantité de mouvement est située à l'intérieur du réservoir respectif opposé à la buse, et un actionneur situé à l'extérieur de la structure de réservoir, permettant d'accélérer les éléments de transfert de quantité de mouvement de haut en bas relativement à la structure de réservoir. Le système ou dispositif de transfert de liquides selon la présente invention peut être utilisé pour transférer des matières biologiques. Le système de transfert de liquide ou dispositif de transfert de liquides selon la présente invention peut également être utilisé pour remplir simultanément un nombre sélectionné ou tout un réseau de récipients de stockage à l'aide de liquide ou pour produire un microréseau sur une surface de substrat. L'invention concerne également une méthode permettant d'améliorer le rendement de distribution d'un dispositif de transfert de liquides. Ladite méthode consiste à accélérer de manière relative un élément de transfert de quantité de mouvement monté dans un réservoir, d'une position de repos vers une buse de sortie du réservoir et à réduire la distance de l'élément de transfert de quantité de mouvement par rapport à la buse de sortie dans la position de repos.
PCT/US2003/017443 2002-06-04 2003-06-04 Dispositif de transfert de liquides WO2003101369A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003249687A AU2003249687A1 (en) 2002-06-04 2003-06-04 Liquid transfer device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US38559802P 2002-06-04 2002-06-04
US60/385,598 2002-06-04

Publications (2)

Publication Number Publication Date
WO2003101369A2 true WO2003101369A2 (fr) 2003-12-11
WO2003101369A3 WO2003101369A3 (fr) 2009-06-18

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Family Applications (1)

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PCT/US2003/017443 WO2003101369A2 (fr) 2002-06-04 2003-06-04 Dispositif de transfert de liquides

Country Status (2)

Country Link
AU (1) AU2003249687A1 (fr)
WO (1) WO2003101369A2 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5320250A (en) * 1991-12-02 1994-06-14 Asymptotic Technologies, Inc. Method for rapid dispensing of minute quantities of viscous material
US5338688A (en) * 1990-08-02 1994-08-16 Boehringer Mannheim Gmbh Method for the metered application of a biochemical analytical liquid to a target

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5338688A (en) * 1990-08-02 1994-08-16 Boehringer Mannheim Gmbh Method for the metered application of a biochemical analytical liquid to a target
US5320250A (en) * 1991-12-02 1994-06-14 Asymptotic Technologies, Inc. Method for rapid dispensing of minute quantities of viscous material

Also Published As

Publication number Publication date
AU2003249687A1 (en) 2003-12-19
WO2003101369A3 (fr) 2009-06-18
AU2003249687A8 (en) 2009-07-30

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