CA2311622A1 - Sub-nanoliter liquid drop dispensing system and method therefor - Google Patents

Sub-nanoliter liquid drop dispensing system and method therefor Download PDF

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Publication number
CA2311622A1
CA2311622A1 CA002311622A CA2311622A CA2311622A1 CA 2311622 A1 CA2311622 A1 CA 2311622A1 CA 002311622 A CA002311622 A CA 002311622A CA 2311622 A CA2311622 A CA 2311622A CA 2311622 A1 CA2311622 A1 CA 2311622A1
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Canada
Prior art keywords
dispensing system
liquid drop
drop dispensing
liquid
sub
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.)
Abandoned
Application number
CA002311622A
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French (fr)
Inventor
Moussa Hoummady
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Individual
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Individual
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 Individual filed Critical Individual
Priority to CA002311622A priority Critical patent/CA2311622A1/en
Priority to PCT/FR2001/001873 priority patent/WO2001096019A1/en
Priority to CA002411748A priority patent/CA2411748A1/en
Priority to ES01945453T priority patent/ES2258533T3/en
Priority to AT01945453T priority patent/ATE317299T1/en
Priority to EP01945453A priority patent/EP1289660B1/en
Priority to US09/882,308 priority patent/US6833112B2/en
Priority to DK01945453T priority patent/DK1289660T3/en
Priority to IL15321601A priority patent/IL153216A0/en
Priority to KR1020027016885A priority patent/KR100780971B1/en
Priority to CNB018111289A priority patent/CN1307001C/en
Priority to DE60117146T priority patent/DE60117146T2/en
Priority to AU2001267673A priority patent/AU2001267673B2/en
Priority to AU6767301A priority patent/AU6767301A/en
Priority to JP2002510191A priority patent/JP2004503389A/en
Publication of CA2311622A1 publication Critical patent/CA2311622A1/en
Priority to IL153216A priority patent/IL153216A/en
Abandoned legal-status Critical Current

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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
    • 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
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • 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
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B01J2219/00317—Microwell devices, i.e. having large numbers of wells
    • 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
    • B01J2219/00364—Pipettes
    • B01J2219/00371—Pipettes comprising electrodes
    • 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
    • B01J2219/00378—Piezo-electric or ink jet dispensers
    • 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
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • 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
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • 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
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • 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
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00608—DNA chips
    • 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
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • 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
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • 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
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides
    • 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
    • B01L2300/0819—Microarrays; Biochips
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
    • 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
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1041—Ink-jet like dispensers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Abstract

A sub-nanoliter liquid drop dispensing system is described herein. The liquid drop dispensing system comprises a plurality of dishes embedded in a substrate, and a deformable membrane covering the dish. The dish includes a tapered liquid sample reservoir provided with a nozzle having an aperture at its narrow end, a pumping section adjacent to the reservoir and a microchannel for handling to the reservoir liquid samples.

Description

TITLE OF THE INVENTION
SUB-NANOLITER LIQUID DROP DISPENSING SYSTEM AND METHOD
THEREFOR
FIELD OF THE INVENTION
The present invention relates to liquid drop dispensing systems. More specifically, the present invention is concerned with a sub-nanoliter liquid drop dispensing system.
BACKGROUND OF THE INVENTION
Recent progress in the genomic field led to increasing speed of expirementation, minimized sample volumes and parallel operation systems. This brought different techniques for biochemical liquid handling, such as micro-spotting systems, micro pipetting with piezoelectric actuators, and more recently, inkjet technology. The driven force for these technologies is micro-array preparation and DNA-Chips preparation by printing, in major cases, pre-synthesized oligonucleotides on a glass or a quartz surface.
Some techniques of the prior-art, such as micro pipetting with piezoelectric actuators and inkjet-based methods, are particularly interesting since they allow dropping of pre-synthesized oligonucleotides or in-situ synthesis.
However, a drawback of such techniques is that the geometry of these liquid dropping systems does not allow both high-speed and high-density screening.
According to high-density criteria combined with short time micro-array preparation, there is a need for Ultra-High Throughput (UHTP) systems, which allow the printing of very small amount of biological samples, in batches, with a spatial resolution comparable to a photo-lithographical method for DNA fixation.
OBJECTS OF THE INVENTION
An object of the present invention is therefore to provide an improved sub-nanoliter liquid drop dispensing system.
BRIEF DESCRIPTION OF THE DRAWINGS
In the appended drawings:
Figure 1 is a sectional view of a sub-nanoliter liquid drop dispensing system according to a first embodiment of the present invention;
Figure 2 is an isometric view of a plurality of dishes of the liquid drop dispensing system of Figure 1;
Figure 3 is an isometric view of a one of the dish of Figure 2;
Figure 4 is a sectional view of a sub-nanoliter liquid drop dispensing system according to a second embodiment of the present invention;
Figure 5 is a sectional view of a sub-nanoliter liquid drop dispensing system according to a third embodiment of the present invention;
Figure 6 is an isometric view of a matrix of pyramidal nozzles according to a first embodiment of the present invention;
Figure ? is an isometric view of a matrix of cylindrical nozzles according to a second embodiment of the present invention.
Figure 8 is a photographic image of a pyramidal nozzle according to the first embodiment of the present invention; and Figure 9 is a photographic image of a pyramidal nozzle according to a second embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Generally stated, the present invention concerns an ultra high throughput, a batch sub-nanoliter liquid drop dispensing system with integrated reservoirs, micro-channels, and individual drop ejection actuators.
Turning now to Figures 1 to 4 of the appended drawings, a sub-nanoliter liquid drop dispensing system 10, according to a first embodiment of the present invention, will be described.
The liquid drop dispensing system 10 comprises a plurality of dishes 12 embedded in a substrate 14 (Figure 2), deformable membranes 16 covering the dish and an actuator in the form of a thin film 17 having magnetic properties.
Turning now to Figure 3, the dish 12 will be described in more detail.
The dish 12 includes a tapered liquid sample reservoir 18 provided with a nozzle 19 (Figure 1 ) and having an aperture 20 at its narrow end, a pumping chamber 22 adjacent to the reservoir 18, and a microchannel 24 for handling liquid samples to the reservoir 18.
Although the reservoir 18 is illustrated as being pyramidal in shape, it may have other configurations, such as cylindrically integrated and cubic without departing from the spirit and nature of the present invention.
The reservoir 18 may advantageously be formed in an 5 etchable material, using, for example, a method that allows the fabrication of microwells with different shapes.
The sizes of the reservoir 18, of the nozzle 19, and of the aperture 20 are chosen according to the application and the desired density.
More specifically, the nozzle 19 is configured and sized to allow control of the droplet sizes. Indeed, droplet size control has been found advantageous, for example, in the field of micro or nano-array printing which allows the density of printable material such DNA Chips to increase. In addition, it has been found advantageous to include a nozzle 19 having a high aspect ratio.
In order to build a matrix of nozzles 19 with high aspect ratio (side walls 26), different methods can be used, such as photolithography bulk and surface micro-machining.
Methods such as wet chemical etching, deep reactive ion etching, electro-forming of materials, electro-discharge micro-machining, molding, hot embossing and polymerization may be used to form the reservoir 18, nozzle 19 and aperture 20.
Figure 6 illustrates a matrix of pyramidal nozzles 40, with individual liquid sample reservoirs according to a first embodiment of the present invention. Each of the pyramidal nozzles includes side walls 42 and an aperture 44.
Figure 7 illustrates a matrix of cylindrical nozzles 48 with individual sample reservoirs 46. Each nozzle 48 includes an aperture 50.
Figure 8 is a photo illustrating a pyramidal nozzle according to the first embodiment of the present invention. The pyramidal nozzle is provided with an aperture 52 of 15x15 Nm2 and is covered with a protective layer of silicon dioxide.
Figure 9 is a photo illustrating a pyramidal nozzle, similar to the nozzle of Figure 8, with an aperture of 5x5 Nm2.
Methods such as electroforming, electroplating and molding allow the fabrication of the nozzle 19 in a different material from that of reservoir 18.
The microchannel 24 can be made of materials such as, for example, glass, quartz, silicon, electroforming materials and PDMS.
The width and depth of the microchannel 24 is typically micrometric and advantageously allows the flow of liquid from input holes (not shown in the figures) to the pumping chamber 22. To prevent sticking of biological samples in the microchannel 24, its inner surfaces are advantageously treated to have specific hydrophobic or hydrophilic properties.
Examples of materials that can be used for the reservoirs 18 or for the microchannels 24 with the pumping chambers 22 include, but are not restricted to, silicium, Si02, Glass, quartz, polymers, resins, plastics and metals (electroformed or processed).
As can be better seen in Figure 1, a membrane 16 is advantageously provided to cover the dishes 12. The deformation of the membrane 16 can trigger either one or both of the following functions:
pumping liquid sample from microchannels and individual drop injection.
The deformation of the membrane 16 is triggered by a thin film 17 having magnetic properties. An electrical coil 28 is advantageously used to selectively generate a magnetic field that allows deformation of the membrane 16 without direct contact. The membrane 16 can advantageously be deformed in both directions.
Other actuators can alternatively be used to cause deformation of the membrane 16, including actuators based on electro-magnetic forces (piezoelectric), thermal expansion, electro-mechanical stress, and electrostatic forces. Any other actuators allowing static or dynamic deformation of the membrane 16 can also be used without departing from the spirit of the present invention.
Figure 4 illustrates the use of a piezoelectric thin film 30, between lower and upper conductive electrodes 32 and 34. The membrane 16 may be deformed by applying a tension between the electrodes 32 and 34. Such actuator allows deformation of the membrane 16 in static or in resonance.
When thermal expansion is used, a thin film, having a thermal expansion coefficient sufficiently different from the one of the membrane 16, is deposited on the membrane 16. Heating of the film will then induce a deformation of the membrane 16.
Alternatively, the membrane 16 and the actuator 17 may be replaced by other means to cause injection of droplets. Such means include an electrical field applied between the reservoir and the liquid sample input reactors to cause electrophoretic mobility, low pressure liquid attraction from the aperture 20 of the nozzle 19, electrospray (allowing extraction of droplets by inducing an electro-magnetic force), and deformation of the aperture 20 or combination thereof. Since these techniques are believed to be well known in the art, they will not be discussed in more detail.
To independently trigger the pumping and the liquid drop injection, independent actuators may be used, as illustrated in Figure16, where an actuator for drop injection 36, and an actuator for liquid sample pumping 38 are shown.
It is to be noted that each ,reservoir 18 may contain different liquid samples. Moreover, the liquid drop dispensing system 10 may advantageously be provided with specific arrangements of connected reservoirs through microchannels (lines, columns or specific blocs).
A liquid drop dispensing system of the present invention allows for example:
~ Injection of droplets in high density with volume of 1 micro liter and 1 hundredth of a picoliter;
~ Individual addressing on demand on an important surface;
~ Integration of all elements of the liquid drop dispensing system that can be processed in whole or in part;
~ Obtaining of hollow injectors that can have an high aspect ratio;
~ Obtaining of injectors having miniature and precise apertures for controlling the size of the liquid droplets;
~ Obtaining of injectors provided with apertures of different sizes;
~ Usage of reservoirs that can include different reagents; and ~ Usage of individual or custom-built injectors.
It is to be noted that the operation of the liquid drop dispensing system may be reversed to pump and then carry small quantities of liquid (for example PCR product) from one place to another.
Indeed, in this case, the liquid is pumped through the apertures 20 to fill the reservoirs 18 from microarray, or by performing a parallel processing such as PCR. The delivery of the liquid is later performed by injection.
A liquid drop dispensing system, according to an embodiment of the present invention, may be used in many applications, 5 including, for example:
~ High speed screening that allows distribution and controlled manipulation of a small quantity of liquid, such as biological substances (including DNA, RNA, 10 proteins, blood, etc.), reagents, drugs and chemical prod ucts;
~ High rate oligonucleotide synthesis to prepare, for example, biomolecular computing devices;
~ Preparation of biomolecular computing devices (DNA, RNA, proteins, etc.);
~ Controlled delivery of medication;
~ Controlled delivery of biological and/or chemical substances in cells or tissues (mechanical injection that can be performed with or without other techniques such as electroporation); and ~ High rate genomic, proteomic, transgenic and in-vitro services.
Although the present invention has been described hereinabove by way of preferred embodiments thereof, it can be modified without departing from the spirit and nature of the subject invention, as defined in the appended claims.

Claims (3)

1. A sub-nanoliter liquid drop dispensing system as described in the present application.
2. A method for dispensing liquid drops as described in the present application.
3. The use of the system described in claim 1 for dispensing drops of oligonucleotides.
CA002311622A 2000-06-15 2000-06-15 Sub-nanoliter liquid drop dispensing system and method therefor Abandoned CA2311622A1 (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
CA002311622A CA2311622A1 (en) 2000-06-15 2000-06-15 Sub-nanoliter liquid drop dispensing system and method therefor
DK01945453T DK1289660T3 (en) 2000-06-15 2001-06-15 High performance system for parallel and selective dispensing of microdroplets
CNB018111289A CN1307001C (en) 2000-06-15 2001-06-15 High-performance system for parallel and selective dispensing of micro-droplets
ES01945453T ES2258533T3 (en) 2000-06-15 2001-06-15 PARALLEL AND SELECTIVE DISTRIBUTION SYSTEM OF HIGH PERFORMANCE MICRO-DROPS.
AT01945453T ATE317299T1 (en) 2000-06-15 2001-06-15 HIGH PERFORMANCE PARALLEL AND SELECTIVE DISTRIBUTION SYSTEM FOR MICRODROPLES
EP01945453A EP1289660B1 (en) 2000-06-15 2001-06-15 High-performance system for parallel and selective dispensing of micro-droplets
US09/882,308 US6833112B2 (en) 2000-06-15 2001-06-15 High performance system for the parallel and selective dispensing of micro-droplets, and transportable cartridge and dispensing kit using said system
PCT/FR2001/001873 WO2001096019A1 (en) 2000-06-15 2001-06-15 High-performance system for parallel and selective dispensing of micro-droplets
IL15321601A IL153216A0 (en) 2000-06-15 2001-06-15 High-performance system for parallel and selective dispensing of micro-droplets
KR1020027016885A KR100780971B1 (en) 2000-06-15 2001-06-15 High-performance system for the parallel and selective dispensing of micro-droplets
CA002411748A CA2411748A1 (en) 2000-06-15 2001-06-15 High-performance system for the parallel and selective dispensing of micro-droplets, and transportable cartridge and dispensing kit
DE60117146T DE60117146T2 (en) 2000-06-15 2001-06-15 System for the parallel and selective distribution of microdroplets
AU2001267673A AU2001267673B2 (en) 2000-06-15 2001-06-15 High-performance system for parallel and selective dispensing of micro-droplets
AU6767301A AU6767301A (en) 2000-06-15 2001-06-15 High-performance system for parallel and selective dispensing of micro-droplets
JP2002510191A JP2004503389A (en) 2000-06-15 2001-06-15 Highly efficient system for parallel and selective dispensing of microdroplets
IL153216A IL153216A (en) 2000-06-15 2002-12-02 High-performance system for parallel and selective dispensing of micro-droplets

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CN1307001C (en) 2007-03-28
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EP1289660B1 (en) 2006-02-08
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KR20030016286A (en) 2003-02-26
KR100780971B1 (en) 2007-11-29
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WO2001096019A1 (en) 2001-12-20
JP2004503389A (en) 2004-02-05

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