US20010055814A1 - Fluid dispenser and dispensing methods - Google Patents

Fluid dispenser and dispensing methods Download PDF

Info

Publication number
US20010055814A1
US20010055814A1 US09/930,590 US93059001A US2001055814A1 US 20010055814 A1 US20010055814 A1 US 20010055814A1 US 93059001 A US93059001 A US 93059001A US 2001055814 A1 US2001055814 A1 US 2001055814A1
Authority
US
United States
Prior art keywords
actuator
fluid
actuators
fluid chamber
volume
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
US09/930,590
Inventor
Glenn Sasaki
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beckman Coulter Inc
Original Assignee
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 US09/930,590 priority Critical patent/US20010055814A1/en
Assigned to AURORA BIOSCIENCES CORPORATION reassignment AURORA BIOSCIENCES CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SASAKI, GLENN C.
Publication of US20010055814A1 publication Critical patent/US20010055814A1/en
Assigned to VERTEX PHARMACEUTICALS (SAN DIEGO) LLC reassignment VERTEX PHARMACEUTICALS (SAN DIEGO) LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: AURORA BIOSCIENCES CORPORATION
Assigned to AURORA DISCOVERY, INC. reassignment AURORA DISCOVERY, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: VERTEX PHARMACEUTICALS (SAN DIEGO) LLC
Priority to US10/929,656 priority patent/US20050032242A1/en
Assigned to OXFORD FINANCE CORPORATION reassignment OXFORD FINANCE CORPORATION SECURITY AGREEMENT Assignors: AURORA DISCOVERY, INC.
Assigned to AURORA DISCOVERY, INC. reassignment AURORA DISCOVERY, INC. RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: OXFORD FINANCE CORPORATION
Assigned to BECKMAN COULTER, INC. reassignment BECKMAN COULTER, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: AURORA DISCOVERY, INC.
Assigned to VERTEX PHARMACEUTICALS (SAN DIEGO) LLC reassignment VERTEX PHARMACEUTICALS (SAN DIEGO) LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: AURORA BIOSCIENCES CORPORATION
Assigned to AURORA DISCOVERY, INC. reassignment AURORA DISCOVERY, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: VERTEX PHARMACEUTICALS (SAN DIEGO) LLC
Abandoned legal-status Critical Current

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065Multiple transfer devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02Burettes; Pipettes
    • B01L3/0241Drop counters; Drop formers
    • B01L3/0268Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00237Handling microquantities of analyte, e.g. microvalves, capillary networks
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/1034Transferring microquantities of liquid
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575Volumetric liquid transfer

Definitions

  • the invention pertains to the controlled dispensing of small volumes of fluid.
  • the invention has particularly advantageous application to automated and integrated systems and methods for rapidly identifying chemicals with biological activity in liquid samples, particularly automated screening of low volume samples for new medicines, agrochemicals, or cosmetics
  • a piezoelectric actuator is coupled to a fluid chamber that contains a nozzle for droplet ejection.
  • a droplet of fluid is ejected through the nozzle.
  • This method of droplet ejection includes several complications, however, such as the production of undesired fluid responses to actuation which interfere with efficient droplet ejection.
  • One possible method of damping undesired fluid responses in a piezoelectrically compressed fluid chamber involves placing selected materials inside or around the rearward portion of the fluid chamber that cushion or passively dampen the pressure wave in the chamber.
  • a fluid dispensing apparatus includes a fluid chamber having an opening for droplet dispensing, a first actuator mechanically coupled to and configured to alter the volume of the fluid chamber, and a second actuator mechanically coupled to and configured to alter the volume the fluid chamber.
  • the apparatus may also include a driver connected to actuate the first and second actuators so as to alter the volume of the fluid chamber, whereby a fluid response produced by the first actuator is damped by the second actuator.
  • the actuators may comprise piezoelectric actuators which are actuated substantially simultaneously or sequentially.
  • Methods of droplet dispensing may comprise altering the volume of a fluid chamber with a first actuator and damping a fluid response to the volume alteration with a second actuator.
  • the altering comprises electrically actuating a first piece of piezoelectric material
  • the damping comprises electrically actuating a second piece of piezoelectric material.
  • FIG. 1 is a block diagram of a dispensing device in accordance with the invention.
  • FIG. 2 is a cross section of a cylindrical droplet dispensing device in accordance with the invention.
  • FIG. 3 is a cross section of a cylindrical drop dispensing device illustrating one embodiment of the electrical connection between piezoelectric actuators and a driver circuit.
  • FIG. 4 is a graphical illustration of one embodiment of a voltage waveform suitable for actuating the piezoelectric actuators of FIGS. 2 and 3.
  • FIG. 5 is a block diagram illustrating a fluid delivery system into which the dispensers of FIGS. 2 and 3 may be advantageously incorporated.
  • FIG. 1 a block diagram representation of a droplet dispensing device according to one embodiment of the invention is shown.
  • the device includes a fluid chamber 10 .
  • This fluid chamber 10 includes an opening (not shown in FIG. 1) from which fluid is ejected.
  • the fluid chamber will also generally be connected to a large volume source of solvent (not shown in FIG. 1) for replenishing expelled fluid.
  • the dispensing device may eject fluid received form this fluid source. In many other instances, however, the fluid ejected from the nozzle will have previously been aspirated into the chamber 10 through the nozzle rather than received from a large volume source.
  • Droplets are dispensed from the fluid chamber by altering the fluid chamber volume with actuators which are mechanically coupled to the fluid chamber. This may be done by compressing the chamber so as to squeeze out a droplet, and then letting the chamber expand to its original volume. This may also be done by first expanding the chamber so as to draw additional fluid from the large volume source, and then letting the chamber contract to its original volume so as to squeeze out a droplet.
  • the fluid chamber 10 is coupled to two actuators, referred to as a dispensing actuator 12 , and a damping actuator 16 (as represented schematically by the arrows pointing toward the fluid chamber 10 ).
  • a dispensing actuator 12 and a damping actuator 16 together provide efficient droplet dispensing without the drawbacks associated with prior art dispensing apparati.
  • the dispensing actuator 12 may be more closely associated with the ejection nozzle of the fluid chamber than the damping actuator 16 , and may thus be more directly associated with droplet ejection.
  • the damping actuator 16 has the principal function of damping a fluid response to actuation of the dispensing actuator 12 .
  • the fluid response damped by the damping actuator 16 may advantageously be a response that otherwise reduces the efficiency of droplet ejection. It will be appreciated by those of skill in the art, however, that the labels “dispensing” and “damping” for the two actuators are not mutually exclusive. In particular, it will be appreciated that both actuators 12 and 16 are involved in the dispensing function and that each may be considered to perform a damping function with regard to a fluid response produced by the other actuator.
  • actuators and methods of coupling actuators to fluid chambers have been devised and are known in the art.
  • the actuators used are made of a piezoelectric material which expands, bends, leans, or otherwise deforms in response to an applied voltage.
  • the actuators are flexing planar membranes.
  • the actuator undergoes a piston-like motion to eject a droplet.
  • the walls of the fluid chamber are themselves made of a piezoelectric material.
  • each individual actuator 12 , 16 and its coupling to the fluid chamber 10 may be implemented using any actuation technique which suits the desired dispensing application.
  • FIG. 2 One specific embodiment of a dispensing apparatus which utilizes the principles discussed with regard to FIG. 1 above is illustrated in cross section in FIG. 2.
  • This embodiment comprises a substantially cylindrical capillary 20 made of any number of suitable materials such as quartz or glass.
  • the capillary 20 has a tapered end 22 which terminates in an opening 24 which forms the nozzle from which droplets of fluid 26 are dispensed.
  • the capillary 20 Surrounding the capillary 20 are two cylindrical piezoelectric actuators 28 , 30 . One of these actuators 28 is positioned closer to the opening 24 than the other actuator 30 .
  • the lower actuator 28 may be actuated so as to compress the region of the capillary 20 inside the lower actuator 28 . When this occurs, pressure waves force fluid both downward toward the nozzle 24 in the direction of the arrow 32 and upward away from the nozzle 24 and toward the second actuator 30 .
  • the upper actuator 30 may also be actuated, producing pressure waves which force fluid downward toward the first actuator 28 in the direction of arrow 36 as well as upward out of the second actuator 30 in the direction of arrow 38 .
  • a constriction may be designed to function to isolate the lower region of the capillary to enhance the efficiency of droplet ejection, but inhibits the ability to remove trapped particulates from the system. Also, the constriction adds to the cost of manufacturing the capillary.
  • the “virtual constriction” produced by the second actuator 30 improves dispensing efficiency so that both actuators 28 , 30 can be moved farther away from the nozzle 24 and still controllably eject fluid droplets. Moving the actuators farther from the nozzle is advantageous because the capillary 20 may extend further down into sample wells during aspiration and fluid dispensing.
  • the capillary 20 comprises a quartz tube having an approximately 1 mm outer diameter and an approximately 0.82 mm inner diameter, tapering down to a nozzle with a diameter of approximately 70 microns.
  • the actuators 28 , 30 comprise approximately 12 mm long cylindrical shells of piezoelectric material such as lead-zirconium-titanate (PZT) having an approximately 1.14 mm inner diameter and a 2.13 mm outer diameter. These dimensions may, of course, vary widely depending on the desired drop volumes.
  • the actuators may be mounted on the capillary 20 such that the lowest extent of the lower actuator 28 is more than 10 mm away from the nozzle 24 .
  • the lowest extent of the lower actuator 28 is more than 20 mm away from the nozzle 24 , with approximately 16 mm away having been found suitable in one specific embodiment.
  • the actuators 28 , 30 may be separated by anywhere from 0 to 10 or more mm. In one embodiment, approximately 3 mm has been found suitable. They may be held in place on the capillary 20 with a small amount of epoxy or other suitable adhesive.
  • cylindrical piezoelectric actuators may be provided with two electrodes, one on the inner surface, and one on the outer surface.
  • the material is polarized radially such that the application of a voltage of the correct polarity produces a radial expansion of the material. This expansion may be used to compress a fluid filled capillary such as is illustrated in FIG. 2.
  • FIG. 3 another cross section is set forth, again showing the piezoelectric actuators 28 , 30 which surround the capillary 20 .
  • the actuators 28 , 30 are each provided with an outer electrode 42 , 44 respectively and an inner electrode 46 , 48 respectively.
  • the electrodes may advantageously comprise a nickel plating.
  • the actuators 28 , 30 , and the electrodes 42 , 44 , 46 , and 48 are shown much thicker than in reality for clarity of illustration.
  • the actuators 28 , 30 are connected to a driver circuit in parallel.
  • a first wire 54 is soldered to the outer electrode 42 of the first actuator 28 and the outer electrode 44 of the second actuator 30 .
  • a second wire 56 is soldered to the inner electrode 46 of the first actuator 28 and the inner electrode 48 of the second actuator 30 .
  • the solder connections to the inner electrode may advantageously be made to the outer portions 50 , 52 of the inner electrodes 46 , 48 .
  • the wires 54 , 56 are connected to a driver circuit which applies a voltage pulse to the electrodes to compress the capillary 20 and eject the droplets as described above in conjunction with FIG. 2.
  • FIG. 4 One embodiment of a voltage waveform which has been found suitable for use with the dispensing device of FIGS. 2 and 3 is illustrated in FIG. 4.
  • the pulse shown is applied such that the positive electrode is on the inner surface of the actuators 28 , 30 , and the ground electrode is on the outer surface of the actuators 28 , 30 .
  • the height 62 of the waveform may be approximately 60 to 150 V with a rise time of about 70 microseconds or less. In general, with a faster rise time, the height 62 of the pulse may be reduced while still producing acceptable droplet formation.
  • the duration 64 of the pulse may be from 20 or 30 microseconds up to one millisecond or more. 500 microseconds has been found suitable in one specific embodiment.
  • the pulse is preferably ramped downward somewhat slowly from its peak value to help eliminate multiple droplet ejection with a single pulse.
  • the voltage drops approximately exponentially to essentially zero in approximately 1 or more milliseconds, with approximately 2 milliseconds having been found suitable in one embodiment. This decay can also be significantly shorter than 1 millisecond while retaining the desired effect.
  • each dispensing device can be separately calibrate such that a known volume of fluid is dispensed with each pulse for each dispensing device produced. This may be done by measuring drop volume as a function of pulse height 62 , and subsequently driving the device during use with a pulse having a height determined to produce the selected drop volume.
  • nanoliter dispensers as described herein can dispense less than approximately 500 nanoliters, more preferably less than approximately 100 nanoliters, and most preferably less than approximately 25 nanoliters.
  • minimal volumes dispensed are 5 nanoliters, 500 picoliters, 100 picoliters, 10 picoliters. It is understood that dispensers capable of dispensing such minimal volumes are also capable of dispensing greater volumes.
  • the volume dispensed with each pulse will be largely dependent on the pulse height, capillary size, and actuator position.
  • Maximum volumes dispensed are about 10.0 microliters, 1.0 microliters, and 200 nanoliters. In the specific 1 mm outer diameter capillary embodiment described with reference to FIGS. 2, 3, and 4 , dispensed volume will typically range from approximately 50 to 400 picoliters. Duty cycle may range from 10 pulses per second to 1000 or more pulses per second, depending on the driving pulse width illustrated in FIG. 4. In one specific embodiment, 100 droplet dispenses per second is utilized.
  • Alternative actuator driving schemes may also be used in addition to the substantially simultaneous driving described above.
  • the upper actuator 30 may be pulsed slightly ahead of the lower actuator so that the downwardly directed fluid responses add together to enhance the efficiency of droplet formation. This may be especially advantageous when more viscous fluids are being ejected.
  • Different pulse shapes may also be used for the different actuators.
  • configurations having three or more simultaneously or sequentially driven actuators may be utilized.
  • the fluid dispensing apparatus described with reference to FIGS. 1 through 3 finds especially advantageous application to high throughput chemical screening apparatus.
  • An example of such an application is presented in FIG. 5.
  • the dispensing apparatus described above may advantageously be incorporated into a sample distribution module in a chemical screening apparatus that can dispense or aspirate large numbers of solutions, usually small volume solutions.
  • the sample distribution module will hold large numbers of different stock solutions of chemicals dissolved in aqueous or non-aqueous solvents (e.g., water or dimethylsulfoxide (DMSO)) in addressable chemical wells.
  • aqueous or non-aqueous solvents e.g., water or dimethylsulfoxide (DMSO)
  • the sample distribution module to aspirate a stock solution from an addressable well and dispense all or a portion of that solution into an addressable sample well or another addressable well.
  • This sequence of events can be progammably controlled to ensure that the stock solution is aspirated from a pre-selected addressable chemical well and is dispensed into a pre-selected addressable sample well.
  • a chemical screening system with these features is described in co-pending and co-owned PCT Patent Application No. PCT/US98/09526, filed May 14, 1998 and entitled “Systems and Methods for Rapidly Identifying Useful Chemicals in Liquid Samples” by Stylli et al.
  • This screening system may advantageously incorporate the droplet dispensing apparatus described herein.
  • the “Systems and Methods for Rapidly Identifying Useful Chemicals in Liquid Samples” patent application is hereby incorporated by reference in its entirety.
  • the system may comprise a plurality of nanoliter dispensers that can individually dispense a predetermined volume.
  • dispensers are arranged in two-dimension array to handle plates of different well densities (e.g., 96, 384, 864 and 3,456).
  • a 96 dispenser array 70 is illustrated, shown as 8 sets of 12 dispensers, with each set being designated by a letter A through H.
  • the dispensers are coupled to a set of feed lines 71 . This coupling may be performed in any number of ways well known or devisable by those of skill in the art.
  • the portion of the dispenser comprising the actuators and wiring illustrated in FIG.
  • a hollow plastic casing which contains integral terminals for the wires 54 , 56 , and an integral stainless steel sleeve which has one end that slides snugly over the end of the capillary 20 opposite the nozzle and has another end that extends out of the plastic casing.
  • the case is filled with epoxy potting and cured to secure solder joints between the wires and the terminals, and to seal the coupling between the quartz capillary and the stainless steel tube.
  • the feed lines 71 may then be secured over the stainless steel tubes to provide a sealed fluid coupling between each dispenser and a source of solvent.
  • the terminals provided with the plastic casing may be connected to a driver circuit provided as part of the screening so as to provide electrical actuation to the piezoelectric elements inside.
  • the dispensers receive solvent such as water or DMSO from a vented reservoir 72 .
  • the vented reservoir includes a liquid level sensor 74 .
  • the height of the solvent in the reservoir 72 is maintained at a level of approximately 12 to 25 mm below the level of the nozzles of the dispensers in the array 70 . This maintains a slight negative pressure in the capillary, and results in an advantageous slightly inwardly directed meniscus in the solvent at the nozzle of each dispenser.
  • the fluid level in the vented reservoir 72 is maintained by periodic refilling from a large solvent reservoir 76 which is pressurized by, for example, a source of compressed air 78 regulated to 5 psi. If the level sensor 74 senses too low a level of solvent in the vented reservoir 72 , a valve 80 will route a portion of the pressurized solvent to the vented reservoir 72 .
  • Each dispenser in a set of 12 is connected via its associated feed line 71 to a port on a commercially available dispenser valve 82 .
  • This valve 82 includes a selected outlet 83 and a common outlet 84 .
  • the valve 82 is configured to provide a fluid coupling between the selected outlet 83 and a user selected port, while connecting all other ports to the common outlet 84 .
  • port 85 is “selected”, and the remainder are connected to the “common”.
  • the common outlet 84 of the dispenser valve 82 is coupled to the vented solvent reservoir 72 through a second valve 86 .
  • the 96 dispensers in the array 70 are fed from 8 separate 16 port dispenser valves, with each dispenser valve coupled to 12 dispensers.
  • Ports 13 - 16 of the dispenser valves 82 in this embodiment are plugged off.
  • the common outlet of each of the 8 dispenser valves is coupled to one of the ports of the 10 port second valve 86 .
  • the selected outlet of each of the eight dispenser valves is connected to a pressure sensor 87 and to respective negative pressure devices 88 .
  • the eight negative pressure devices may advantageously comprise syringe pumps.
  • the apparatus preferably will both aspirate reagent up into the capillaries, and dispense reagent from the capillaries.
  • Aspiration of 96 samples may be performed by first selecting port 1 with each dispenser valve 82 . With the dispenser tips placed in the desired sample wells, a volume of fluid is drawn into the eight capillaries connected to a port 1 of each dispenser valve using the eight syringe pumps 88 . Each syringe pump 88 outlet is then switched toward a waste container 90 , and the solvent taken up into the syringe pumps 88 during aspiration is deposited there.
  • port 2 is selected with each dispenser valve 82 .
  • a volume of fluid is drawn into the next eight capillaries using the syringe pumps 88 , and the solvent taken up by the syringe pumps 88 during aspiration is expelled into a waste container 90 .
  • This process is repeated for ports 3 - 12 of the dispenser valves.
  • the dispenser valves 82 are set to select port 13 . This connects all 12 ports 1 - 12 to the vented reservoir 72 . With the pressure in the capillaries thus equilibrated to the pressure in the vented reservoir 72 , the actuators are pulsed as described above, and 96 volumes of fluid are simultaneously dispensed.
  • a forward flush process may be performed by sealing and pressurizing the vented reservoir 72 . Pressurization may be performed by venting the solvent container 72 through a valve 92 which is coupled to both the ambient atmosphere and to the 5 psi compressed air source 78 . During this forward flush procedure, if the all of the dispenser valves 82 are configured to select port 13 , all 96 dispensers will be coupled to the previously vented (but now pressurized) solvent reservoir 72 .
  • a reverse flush process may be performed by repeating the aspiration technique described above a desired number of times.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Reciprocating Pumps (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)
  • Coating Apparatus (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

A fluid dispenser comprises a fluid chamber having two actuators coupled thereto. One of the actuators damps a fluid response of the other. The fluid chamber may comprises a cylindrical capillary, and the actuators may comprise spaced cylindrical piezoelectric elements.

Description

    RELATED APPLICATIONS
  • The present application is a continuation of U.S. application Ser. No. 09/210,260, filed on Dec. 10, 1998, by Sasaki, and entitled “FLUID DISPENSER AND DISPENSING METHODS,” the disclosure of which is incorporated herein by reference in its entirety.[0001]
  • TECHNICAL FIELD
  • The invention pertains to the controlled dispensing of small volumes of fluid. The invention has particularly advantageous application to automated and integrated systems and methods for rapidly identifying chemicals with biological activity in liquid samples, particularly automated screening of low volume samples for new medicines, agrochemicals, or cosmetics [0002]
  • Introduction
  • The dispensing of small volumes of fluids is an important aspect of several different technologies, from various printing techniques to chemical screening apparatus for drug discovery. Thus, systems and methods for controllably and accurately dispensing liquid, especially small liquid samples, can benefit a number of different fields. The agrochemical, pharmaceutical, and cosmetic fields all have applications where large numbers of liquid samples containing chemicals are processed. In some instances, the processing of liquid samples, such as in pharmaceutical arts, which usually demands complicated liquid processing for drug discovery, can obtain throughput rates of approximately 10,000 samples per day or greater. [0003]
  • A wide variety of designs for dispensers have been utilized. In some applications, a piezoelectric actuator is coupled to a fluid chamber that contains a nozzle for droplet ejection. When the piezoelectric material is actuated, a droplet of fluid is ejected through the nozzle. Such a system is illustrated in U.S. Pat. No. 4,877,745 to Hayes, et al., which is incorporated herein by reference in its entirety. [0004]
  • This method of droplet ejection includes several complications, however, such as the production of undesired fluid responses to actuation which interfere with efficient droplet ejection. One possible method of damping undesired fluid responses in a piezoelectrically compressed fluid chamber involves placing selected materials inside or around the rearward portion of the fluid chamber that cushion or passively dampen the pressure wave in the chamber. Some of these techniques are described, for example, in U.S. Pat. Nos. 3,832,579 to Arndt, 4,233,610 to Fischbeck et al., and 4,528,579 to Brescia. However, these passive systems are relatively expensive to implement, and may need significant alteration depending on the physical properties of the fluid being dispensed. [0005]
  • Another proposed solution to undesired fluid responses, illustrated in U.S. Pat. No. 4,418,354 to Perduijn (which is hereby incorporated into the present disclosure by reference), involves placing a fluid flow restriction in a portion of the fluid chamber rearward from the nozzle. A dispensing apparatus with a similar functional constriction is commercially available from Packard Instrument Company of Meridan, Conn. as an accessory to the MultiProbe [0006] 104. The presence of the restriction, however, produces additional difficulties, such as inhibiting removal of particulate matter that may become inadvertently introduced into the fluid chamber. Once a particle gets inside the fluid chamber, it may become trapped between the small diameter nozzle and small diameter restriction, thereby clogging the device and interfering with the proper operation of the dispenser.
  • A need therefore exists for efficient droplet dispensing devices which do not suffer from the above mentioned drawbacks. [0007]
  • SUMMARY OF THE INVENTION
  • The invention is directed to method and apparatus for fluid dispensing. In one embodiment a fluid dispensing apparatus includes a fluid chamber having an opening for droplet dispensing, a first actuator mechanically coupled to and configured to alter the volume of the fluid chamber, and a second actuator mechanically coupled to and configured to alter the volume the fluid chamber. The apparatus may also include a driver connected to actuate the first and second actuators so as to alter the volume of the fluid chamber, whereby a fluid response produced by the first actuator is damped by the second actuator. The actuators may comprise piezoelectric actuators which are actuated substantially simultaneously or sequentially. [0008]
  • Methods of droplet dispensing may comprise altering the volume of a fluid chamber with a first actuator and damping a fluid response to the volume alteration with a second actuator. In one specific embodiment, the altering comprises electrically actuating a first piece of piezoelectric material, and wherein the damping comprises electrically actuating a second piece of piezoelectric material.[0009]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 is a block diagram of a dispensing device in accordance with the invention. [0010]
  • FIG. 2 is a cross section of a cylindrical droplet dispensing device in accordance with the invention. [0011]
  • FIG. 3 is a cross section of a cylindrical drop dispensing device illustrating one embodiment of the electrical connection between piezoelectric actuators and a driver circuit. [0012]
  • FIG. 4 is a graphical illustration of one embodiment of a voltage waveform suitable for actuating the piezoelectric actuators of FIGS. 2 and 3. [0013]
  • FIG. 5 is a block diagram illustrating a fluid delivery system into which the dispensers of FIGS. 2 and 3 may be advantageously incorporated.[0014]
  • DETAILED DESCRIPTION OF THE INVENTION
  • Embodiments of the invention will now be described with reference to the accompanying Figures, wherein like numerals refer to like elements throughout. The terminology used in the description presented herein is not intended to be interpreted in any limited or restrictive manner, simply because it is being utilized in conjunction with a detailed description of certain specific embodiments of the invention. Furthermore, embodiments of the invention may include several novel features, no single one of which is solely responsible for its desirable attributes or which is essential to practicing the inventions herein described. [0015]
  • Referring now to FIG. 1, a block diagram representation of a droplet dispensing device according to one embodiment of the invention is shown. The device includes a [0016] fluid chamber 10. This fluid chamber 10 includes an opening (not shown in FIG. 1) from which fluid is ejected. The fluid chamber will also generally be connected to a large volume source of solvent (not shown in FIG. 1) for replenishing expelled fluid. The dispensing device may eject fluid received form this fluid source. In many other instances, however, the fluid ejected from the nozzle will have previously been aspirated into the chamber 10 through the nozzle rather than received from a large volume source.
  • Droplets are dispensed from the fluid chamber by altering the fluid chamber volume with actuators which are mechanically coupled to the fluid chamber. This may be done by compressing the chamber so as to squeeze out a droplet, and then letting the chamber expand to its original volume. This may also be done by first expanding the chamber so as to draw additional fluid from the large volume source, and then letting the chamber contract to its original volume so as to squeeze out a droplet. [0017]
  • In many prior art designs, when the fluid chamber is compressed by actuation, the fluid will not only be forced in a forward direction toward the nozzle, but will also be forced backward away from the nozzle at the same time. This rearwardly directed fluid response hinders the capacity of the nozzle directed fluid response to overcome fluid surface tension at the nozzle. Droplet ejection can be therefore inefficient and may even be impossible. [0018]
  • In the embodiment of FIG. 1, however, the [0019] fluid chamber 10 is coupled to two actuators, referred to as a dispensing actuator 12, and a damping actuator 16 (as represented schematically by the arrows pointing toward the fluid chamber 10). These two actuators 12, 16 together provide efficient droplet dispensing without the drawbacks associated with prior art dispensing apparati. In some embodiments, the dispensing actuator 12 may be more closely associated with the ejection nozzle of the fluid chamber than the damping actuator 16, and may thus be more directly associated with droplet ejection. In these embodiments, the damping actuator 16 has the principal function of damping a fluid response to actuation of the dispensing actuator 12. The fluid response damped by the damping actuator 16 may advantageously be a response that otherwise reduces the efficiency of droplet ejection. It will be appreciated by those of skill in the art, however, that the labels “dispensing” and “damping” for the two actuators are not mutually exclusive. In particular, it will be appreciated that both actuators 12 and 16 are involved in the dispensing function and that each may be considered to perform a damping function with regard to a fluid response produced by the other actuator. One beneficial aspect of the dispensing apparatus illustrated in FIG. 1, however, is that fluid responses which inhibit droplet ejection are predominantly damped, thereby increasing the efficiency of droplet ejection in an inexpensive manner which avoids problems with prior art apparatus.
  • It will be appreciated by those in the art that a wide variety of actuators and methods of coupling actuators to fluid chambers have been devised and are known in the art. In most instances, the actuators used are made of a piezoelectric material which expands, bends, leans, or otherwise deforms in response to an applied voltage. In some cases, the actuators are flexing planar membranes. In others, the actuator undergoes a piston-like motion to eject a droplet. In still other cases, the walls of the fluid chamber are themselves made of a piezoelectric material. It will be appreciated that each [0020] individual actuator 12, 16 and its coupling to the fluid chamber 10 may be implemented using any actuation technique which suits the desired dispensing application.
  • One specific embodiment of a dispensing apparatus which utilizes the principles discussed with regard to FIG. 1 above is illustrated in cross section in FIG. 2. This embodiment comprises a substantially [0021] cylindrical capillary 20 made of any number of suitable materials such as quartz or glass. The capillary 20 has a tapered end 22 which terminates in an opening 24 which forms the nozzle from which droplets of fluid 26 are dispensed.
  • Surrounding the capillary [0022] 20 are two cylindrical piezoelectric actuators 28, 30. One of these actuators 28 is positioned closer to the opening 24 than the other actuator 30. In operation, the lower actuator 28 may be actuated so as to compress the region of the capillary 20 inside the lower actuator 28. When this occurs, pressure waves force fluid both downward toward the nozzle 24 in the direction of the arrow 32 and upward away from the nozzle 24 and toward the second actuator 30. The upper actuator 30 may also be actuated, producing pressure waves which force fluid downward toward the first actuator 28 in the direction of arrow 36 as well as upward out of the second actuator 30 in the direction of arrow 38.
  • The net effect of the actuation of both [0023] actuators 28 and 30 is that the fluid response to the first actuator 28 which is directed upward and away from the nozzle is damped by the presence of the downwardly directed fluid response produced by the second actuator 30. This isolates the lower portion of the capillary 20, prevents significant fluid flow away from the nozzle, and allows the lower actuator 28 to efficiently produce a pressure pulse in the region of the nozzle 24 which can overcome the surface tension of the fluid and eject a droplet 26.
  • Several advantages to the designs described herein over the prior art are apparent. First, no constriction needs to be present in the capillary [0024] 20 in the region upward from the nozzle 24. As described above, a constriction may be designed to function to isolate the lower region of the capillary to enhance the efficiency of droplet ejection, but inhibits the ability to remove trapped particulates from the system. Also, the constriction adds to the cost of manufacturing the capillary. In addition, the “virtual constriction” produced by the second actuator 30 improves dispensing efficiency so that both actuators 28, 30 can be moved farther away from the nozzle 24 and still controllably eject fluid droplets. Moving the actuators farther from the nozzle is advantageous because the capillary 20 may extend further down into sample wells during aspiration and fluid dispensing.
  • In one specific embodiment, the capillary [0025] 20 comprises a quartz tube having an approximately 1 mm outer diameter and an approximately 0.82 mm inner diameter, tapering down to a nozzle with a diameter of approximately 70 microns. The actuators 28, 30 comprise approximately 12 mm long cylindrical shells of piezoelectric material such as lead-zirconium-titanate (PZT) having an approximately 1.14 mm inner diameter and a 2.13 mm outer diameter. These dimensions may, of course, vary widely depending on the desired drop volumes. The actuators may be mounted on the capillary 20 such that the lowest extent of the lower actuator 28 is more than 10 mm away from the nozzle 24. In some embodiments, the lowest extent of the lower actuator 28 is more than 20 mm away from the nozzle 24, with approximately 16 mm away having been found suitable in one specific embodiment. The actuators 28, 30 may be separated by anywhere from 0 to 10 or more mm. In one embodiment, approximately 3 mm has been found suitable. They may be held in place on the capillary 20 with a small amount of epoxy or other suitable adhesive.
  • Turning now to FIGS. 3 and 4, actuation of the [0026] piezoelectric actuators 28, 30 will be described. As is well known in the art, cylindrical piezoelectric actuators may be provided with two electrodes, one on the inner surface, and one on the outer surface. The material is polarized radially such that the application of a voltage of the correct polarity produces a radial expansion of the material. This expansion may be used to compress a fluid filled capillary such as is illustrated in FIG. 2. In FIG. 3, another cross section is set forth, again showing the piezoelectric actuators 28, 30 which surround the capillary 20.
  • The [0027] actuators 28, 30 are each provided with an outer electrode 42, 44 respectively and an inner electrode 46, 48 respectively. The electrodes may advantageously comprise a nickel plating. For convenient access to the inner electrodes 46, 48, it is common to wrap the inner electrode plating around one end of the actuator to provide electrode portions 50, 52 which are on the outer surface of the actuators 28, 30, but which are electrically connected to the inner electrodes 46, 48. It will be appreciated that in FIG. 3, the actuators 28, 30, and the electrodes 42, 44, 46, and 48 are shown much thicker than in reality for clarity of illustration.
  • It has been found that simultaneous actuation of both [0028] actuators 28, 30 produces the advantageous features of the dual actuator configuration described above. Accordingly, and as illustrated in FIG. 3, the actuators 28, 30 are connected to a driver circuit in parallel. In particular, a first wire 54 is soldered to the outer electrode 42 of the first actuator 28 and the outer electrode 44 of the second actuator 30. In addition, a second wire 56 is soldered to the inner electrode 46 of the first actuator 28 and the inner electrode 48 of the second actuator 30. The solder connections to the inner electrode may advantageously be made to the outer portions 50, 52 of the inner electrodes 46, 48. The wires 54, 56 are connected to a driver circuit which applies a voltage pulse to the electrodes to compress the capillary 20 and eject the droplets as described above in conjunction with FIG. 2.
  • One embodiment of a voltage waveform which has been found suitable for use with the dispensing device of FIGS. 2 and 3 is illustrated in FIG. 4. The pulse shown is applied such that the positive electrode is on the inner surface of the [0029] actuators 28, 30, and the ground electrode is on the outer surface of the actuators 28, 30. The height 62 of the waveform may be approximately 60 to 150 V with a rise time of about 70 microseconds or less. In general, with a faster rise time, the height 62 of the pulse may be reduced while still producing acceptable droplet formation. The duration 64 of the pulse may be from 20 or 30 microseconds up to one millisecond or more. 500 microseconds has been found suitable in one specific embodiment. The pulse is preferably ramped downward somewhat slowly from its peak value to help eliminate multiple droplet ejection with a single pulse. In one embodiment, the voltage drops approximately exponentially to essentially zero in approximately 1 or more milliseconds, with approximately 2 milliseconds having been found suitable in one embodiment. This decay can also be significantly shorter than 1 millisecond while retaining the desired effect.
  • Because material and manufacturing variations will affect droplet size and efficiency of ejection, it can be advantageous to separately calibrate each dispensing device such that a known volume of fluid is dispensed with each pulse for each dispensing device produced. This may be done by measuring drop volume as a function of [0030] pulse height 62, and subsequently driving the device during use with a pulse having a height determined to produce the selected drop volume.
  • In reagent dispensing environments, for example, it is usually advantageous to dispense less than approximately 2,000 nanoliters of liquid with each pulse. Preferably, nanoliter dispensers as described herein can dispense less than approximately 500 nanoliters, more preferably less than approximately 100 nanoliters, and most preferably less than approximately 25 nanoliters. Preferred, minimal volumes dispensed are 5 nanoliters, 500 picoliters, 100 picoliters, 10 picoliters. It is understood that dispensers capable of dispensing such minimal volumes are also capable of dispensing greater volumes. The volume dispensed with each pulse will be largely dependent on the pulse height, capillary size, and actuator position. Maximum volumes dispensed are about 10.0 microliters, 1.0 microliters, and 200 nanoliters. In the specific 1 mm outer diameter capillary embodiment described with reference to FIGS. 2, 3, and [0031] 4, dispensed volume will typically range from approximately 50 to 400 picoliters. Duty cycle may range from 10 pulses per second to 1000 or more pulses per second, depending on the driving pulse width illustrated in FIG. 4. In one specific embodiment, 100 droplet dispenses per second is utilized.
  • Alternative actuator driving schemes may also be used in addition to the substantially simultaneous driving described above. For example, it may be desirable to independently drive the [0032] piezoelectric actuators 28, 30. They may, for example, be driven sequentially. In these embodiments, the upper actuator 30 may be pulsed slightly ahead of the lower actuator so that the downwardly directed fluid responses add together to enhance the efficiency of droplet formation. This may be especially advantageous when more viscous fluids are being ejected. Different pulse shapes may also be used for the different actuators. Furthermore, configurations having three or more simultaneously or sequentially driven actuators may be utilized.
  • As mentioned above, the fluid dispensing apparatus described with reference to FIGS. 1 through 3 finds especially advantageous application to high throughput chemical screening apparatus. An example of such an application is presented in FIG. 5. The dispensing apparatus described above may advantageously be incorporated into a sample distribution module in a chemical screening apparatus that can dispense or aspirate large numbers of solutions, usually small volume solutions. In many instances, the sample distribution module will hold large numbers of different stock solutions of chemicals dissolved in aqueous or non-aqueous solvents (e.g., water or dimethylsulfoxide (DMSO)) in addressable chemical wells. To facilitate the rapid transfer of these stock solutions, it is desirable for the sample distribution module to aspirate a stock solution from an addressable well and dispense all or a portion of that solution into an addressable sample well or another addressable well. This sequence of events can be progammably controlled to ensure that the stock solution is aspirated from a pre-selected addressable chemical well and is dispensed into a pre-selected addressable sample well. A chemical screening system with these features is described in co-pending and co-owned PCT Patent Application No. PCT/US98/09526, filed May 14, 1998 and entitled “Systems and Methods for Rapidly Identifying Useful Chemicals in Liquid Samples” by Stylli et al. This screening system may advantageously incorporate the droplet dispensing apparatus described herein. The “Systems and Methods for Rapidly Identifying Useful Chemicals in Liquid Samples” patent application is hereby incorporated by reference in its entirety. [0033]
  • In one embodiment, the system may comprise a plurality of nanoliter dispensers that can individually dispense a predetermined volume. Typically, dispensers are arranged in two-dimension array to handle plates of different well densities (e.g., 96, 384, 864 and 3,456). In FIG. 5, a 96 [0034] dispenser array 70 is illustrated, shown as 8 sets of 12 dispensers, with each set being designated by a letter A through H. The dispensers are coupled to a set of feed lines 71. This coupling may be performed in any number of ways well known or devisable by those of skill in the art. In one embodiment, the portion of the dispenser comprising the actuators and wiring illustrated in FIG. 3 is placed in a hollow plastic casing which contains integral terminals for the wires 54, 56, and an integral stainless steel sleeve which has one end that slides snugly over the end of the capillary 20 opposite the nozzle and has another end that extends out of the plastic casing. The case is filled with epoxy potting and cured to secure solder joints between the wires and the terminals, and to seal the coupling between the quartz capillary and the stainless steel tube. The feed lines 71 may then be secured over the stainless steel tubes to provide a sealed fluid coupling between each dispenser and a source of solvent. Furthermore, the terminals provided with the plastic casing may be connected to a driver circuit provided as part of the screening so as to provide electrical actuation to the piezoelectric elements inside.
  • The dispensers receive solvent such as water or DMSO from a vented [0035] reservoir 72. The vented reservoir includes a liquid level sensor 74. The height of the solvent in the reservoir 72 is maintained at a level of approximately 12 to 25 mm below the level of the nozzles of the dispensers in the array 70. This maintains a slight negative pressure in the capillary, and results in an advantageous slightly inwardly directed meniscus in the solvent at the nozzle of each dispenser.
  • The fluid level in the vented [0036] reservoir 72 is maintained by periodic refilling from a large solvent reservoir 76 which is pressurized by, for example, a source of compressed air 78 regulated to 5 psi. If the level sensor 74 senses too low a level of solvent in the vented reservoir 72, a valve 80 will route a portion of the pressurized solvent to the vented reservoir 72.
  • Each dispenser in a set of 12 is connected via its associated [0037] feed line 71 to a port on a commercially available dispenser valve 82. This valve 82 includes a selected outlet 83 and a common outlet 84. The valve 82 is configured to provide a fluid coupling between the selected outlet 83 and a user selected port, while connecting all other ports to the common outlet 84. In FIG. 5, port 85 is “selected”, and the remainder are connected to the “common”. The common outlet 84 of the dispenser valve 82 is coupled to the vented solvent reservoir 72 through a second valve 86. In this embodiment, the 96 dispensers in the array 70 are fed from 8 separate 16 port dispenser valves, with each dispenser valve coupled to 12 dispensers. Ports 13-16 of the dispenser valves 82 in this embodiment are plugged off. The common outlet of each of the 8 dispenser valves is coupled to one of the ports of the 10 port second valve 86. The selected outlet of each of the eight dispenser valves is connected to a pressure sensor 87 and to respective negative pressure devices 88. The eight negative pressure devices may advantageously comprise syringe pumps.
  • As mentioned above, the apparatus preferably will both aspirate reagent up into the capillaries, and dispense reagent from the capillaries. Aspiration of 96 samples may be performed by first selecting [0038] port 1 with each dispenser valve 82. With the dispenser tips placed in the desired sample wells, a volume of fluid is drawn into the eight capillaries connected to a port 1 of each dispenser valve using the eight syringe pumps 88. Each syringe pump 88 outlet is then switched toward a waste container 90, and the solvent taken up into the syringe pumps 88 during aspiration is deposited there.
  • Next, port [0039] 2 is selected with each dispenser valve 82. With the dispenser tips still in the desired sample wells, a volume of fluid is drawn into the next eight capillaries using the syringe pumps 88, and the solvent taken up by the syringe pumps 88 during aspiration is expelled into a waste container 90. This process is repeated for ports 3-12 of the dispenser valves.
  • To dispense the 96 aspirated samples, the [0040] dispenser valves 82 are set to select port 13. This connects all 12 ports 1-12 to the vented reservoir 72. With the pressure in the capillaries thus equilibrated to the pressure in the vented reservoir 72, the actuators are pulsed as described above, and 96 volumes of fluid are simultaneously dispensed.
  • A forward flush process may be performed by sealing and pressurizing the vented [0041] reservoir 72. Pressurization may be performed by venting the solvent container 72 through a valve 92 which is coupled to both the ambient atmosphere and to the 5 psi compressed air source 78. During this forward flush procedure, if the all of the dispenser valves 82 are configured to select port 13, all 96 dispensers will be coupled to the previously vented (but now pressurized) solvent reservoir 72. A reverse flush process may be performed by repeating the aspiration technique described above a desired number of times.
  • All publications and patent documents cited herein are hereby incorporated by reference to the same extent as if they had been individually incorporated by reference. [0042]
  • The foregoing description details certain embodiments of the invention. It will be appreciated, however, that no matter how detailed the foregoing appears in text, the invention can be practiced in many ways. As is also stated above, it should be noted that the use of particular terminology when describing certain features or aspects of the invention should not be taken to imply that the terminology is being re-defined herein to be restricted to including any specific characteristics of the features or aspects of the invention with which that terminology is associated. The scope of the invention should therefore be construed in accordance with the appended claims and any equivalents thereof. [0043]

Claims (27)

What is claimed is:
1. An apparatus for dispensing droplets of fluid comprising:
a fluid chamber having an opening therein for droplet dispensing;
a first actuator mechanically coupled to said fluid chamber and configured to alter the volume thereof;
a second actuator mechanically coupled to said fluid chamber and configured to alter the volume thereof, wherein said second actuator is further away from said opening than said first actuator; and
a driver connected to substantially simultaneously actuate said first and said second actuators so as to dispense fluid droplets from said fluid chamber.
2. The apparatus of
claim 1
, wherein said driver is connected to actuate said second actuator prior to actuating said first actuator.
3. The apparatus of
claim 1
, wherein said first and said second actuators are more than approximately 10 mm away from said opening.
4. An apparatus for dispensing droplets of fluid comprising:
a fluid chamber having an opening therein for droplet dispensing;
a first actuator mechanically coupled to said fluid chamber and configured to alter the volume thereof;
a second actuator mechanically coupled to said fluid chamber and configured to alter the volume thereof; and
a driver connected to actuate said first and said second actuators so as to alter the volume of said fluid chamber, whereby a fluid response produced by said first actuator is damped by said second actuator.
5. The apparatus of
claim 4
, wherein said driver is connected to actuate said first and said second actuators substantially simultaneously.
6. The apparatus of
claim 4
, wherein said driver is connected to actuate said second actuator prior to actuating said first actuator.
7. The apparatus of
claim 4
, wherein said first and said second actuators comprise piezoelectric material.
8. A piezoelectric fluid aspiration and dispensing device comprising a capillary having an opening in one end for aspirating and dispensing fluid, wherein said capillary is at least partially surrounded by a plurality of cylindrical piezoelectric actuators positioned behind said opening, wherein said plurality of cylindrical piezoelectric actuators are coupled to drive circuitry for actuation; and wherein said glass capillary is unrestricted behind said piezoelectric actuators so as to allow aspirated particulate material to flow away from said opening during a reverse flush cycle.
9. The dispensing device of
claim 8
, wherein a first cylindrical piezoelectric actuator extends from approximately 16 mm behind said opening to approximately 29 mm behind said opening.
10. The dispensing device of
claim 9
, wherein a second cylindrical piezoelectric actuator extends from approximately 32 mm behind said opening to approximately 45 mm behind said opening.
11. A method of depositing a volume of fluid comprising compressing a cylindrical capillary with a plurality of cylindrical actuators.
12. The method of
claim 11
, wherein said compressing is performed substantially simultaneously.
13. The method of
claim 11
, wherein a first one of said plurality of cylindrical actuators is actuated before a second one of said plurality of cylindrical actuators.
14. A method of droplet deposition comprising:
altering the volume of a fluid chamber with a first actuator;
damping a fluid response to said volume alteration with a second actuator.
15. The method of
claim 14
, wherein said altering comprises compressing said fluid chamber.
16. The method of
claim 15
, wherein said damping comprises compressing said fluid chamber.
17. The method of
claim 15
, wherein said compressing is performed substantially simultaneously.
18. The method of
claim 17
, wherein said compressing is performed sequentially.
19. The method of
claim 14
, wherein said altering comprises electrically actuating a first piece of piezoelectric material, and wherein said damping comprises electrically actuating a second piece of piezoelectric material.
20. The method of
claim 19
, wherein said actuating a first piece of piezoelectric material and actuating a second piece of piezoelectric material are performed substantially simultaneously.
21. A droplet dispensing apparatus comprising:
a fluid chamber;
a first means for altering the volume of said fluid chamber; and
a second means for altering the volume of said fluid chamber, wherein said second means additionally comprises means for damping a fluid response to said first means.
22. The droplet dispenser of
claim 21
, wherein said first and said second volume altering means comprise piezoelectric material.
23. The droplet dispensing apparatus of
claim 22
, additionally comprising a driver circuit connected in parallel to said first and said second piezoelectric means.
24. A method of making a droplet deposition device comprising:
positioning a first actuator proximate to an ejection nozzle of a fluid chamber;
positioning a second actuator farther from said ejection nozzle than said first actuator; and
connecting both of said actuators to a driver.
25. The method of
claim 24
, wherein said positioning comprises substantially surrounding a glass capillary with cylindrical piezoelectric actuators.
26. The method of
claim 25
, wherein said connecting comprises connecting said piezoelectric actuators in parallel to a voltage source.
27. A droplet dispensing apparatus comprising:
a fluid chamber;
a first piezoelectric means for altering the volume of said fluid chamber; and
a second piezoelectric means for damping a fluid response to said altering.
US09/930,590 1998-12-10 2001-08-15 Fluid dispenser and dispensing methods Abandoned US20010055814A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US09/930,590 US20010055814A1 (en) 1998-12-10 2001-08-15 Fluid dispenser and dispensing methods
US10/929,656 US20050032242A1 (en) 1998-12-10 2004-08-30 Fluid dispenser and dispensing methods

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/210,260 US6296811B1 (en) 1998-12-10 1998-12-10 Fluid dispenser and dispensing methods
US09/930,590 US20010055814A1 (en) 1998-12-10 2001-08-15 Fluid dispenser and dispensing methods

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/210,260 Continuation US6296811B1 (en) 1998-12-10 1998-12-10 Fluid dispenser and dispensing methods

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/929,656 Division US20050032242A1 (en) 1998-12-10 2004-08-30 Fluid dispenser and dispensing methods

Publications (1)

Publication Number Publication Date
US20010055814A1 true US20010055814A1 (en) 2001-12-27

Family

ID=22782204

Family Applications (3)

Application Number Title Priority Date Filing Date
US09/210,260 Expired - Lifetime US6296811B1 (en) 1998-12-10 1998-12-10 Fluid dispenser and dispensing methods
US09/930,590 Abandoned US20010055814A1 (en) 1998-12-10 2001-08-15 Fluid dispenser and dispensing methods
US10/929,656 Abandoned US20050032242A1 (en) 1998-12-10 2004-08-30 Fluid dispenser and dispensing methods

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US09/210,260 Expired - Lifetime US6296811B1 (en) 1998-12-10 1998-12-10 Fluid dispenser and dispensing methods

Family Applications After (1)

Application Number Title Priority Date Filing Date
US10/929,656 Abandoned US20050032242A1 (en) 1998-12-10 2004-08-30 Fluid dispenser and dispensing methods

Country Status (11)

Country Link
US (3) US6296811B1 (en)
EP (2) EP1316361B1 (en)
JP (1) JP2002531259A (en)
AT (2) ATE354440T1 (en)
AU (1) AU3118900A (en)
CA (1) CA2354555C (en)
DE (2) DE69909511T2 (en)
DK (1) DK1137489T3 (en)
ES (2) ES2284995T3 (en)
PT (1) PT1137489E (en)
WO (1) WO2000033961A1 (en)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020106812A1 (en) * 2001-01-26 2002-08-08 Fisher William D. Fluid drop dispensing
WO2002070133A1 (en) * 2001-03-01 2002-09-12 Peter Wiktor Piezoelectric pipetting device housing and methods for making and using the same
US6599479B1 (en) * 1997-12-05 2003-07-29 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Device and procedure for the electrically triggered microdrop release with a dispensing head
US20030167822A1 (en) * 2002-01-25 2003-09-11 Innovadyne Technologies, Inc. Univeral calibration system and method for a high performance, low volume, non-contact liquid dispensing apparatus
US20040050861A1 (en) * 2000-10-24 2004-03-18 Thomas Lisec Pipette system and pipette array
US20050226779A1 (en) * 2003-09-19 2005-10-13 Oldham Mark F Vacuum assist for a microplate
US20060057740A1 (en) * 2002-12-02 2006-03-16 Arkray Method for manufacturing tool for analysis
US7135146B2 (en) 2000-10-11 2006-11-14 Innovadyne Technologies, Inc. Universal non-contact dispense peripheral apparatus and method for a primary liquid handling device
US20070015289A1 (en) * 2003-09-19 2007-01-18 Kao H P Dispenser array spotting
US7427379B1 (en) * 1999-03-19 2008-09-23 Biotage Ab Liquid dispensing apparatus
US7497995B2 (en) 2000-10-11 2009-03-03 Innovadyne Technologies, Inc. Hybrid valve apparatus and method for fluid handling
US20100086977A1 (en) * 2003-09-19 2010-04-08 Life Technologies Corporation Pressure Chamber Clamp Mechanism
US20120304929A1 (en) * 2011-01-21 2012-12-06 Biodot, Inc. Piezoelectric dispenser with a longitudinal transducer and replaceable capillary tube
US10253361B2 (en) 2002-07-30 2019-04-09 Applied Biosystems, Llc Sample block apparatus and method for maintaining a microcard on a sample block

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7214540B2 (en) 1999-04-06 2007-05-08 Uab Research Foundation Method for screening crystallization conditions in solution crystal growth
US7250305B2 (en) * 2001-07-30 2007-07-31 Uab Research Foundation Use of dye to distinguish salt and protein crystals under microcrystallization conditions
US7244396B2 (en) 1999-04-06 2007-07-17 Uab Research Foundation Method for preparation of microarrays for screening of crystal growth conditions
DE10010208C2 (en) * 2000-02-25 2002-02-07 Inst Physikalische Hochtech Ev Microdosing device for the defined delivery of small, closed liquid volumes
US6709872B1 (en) * 2000-05-02 2004-03-23 Irm Llc Method and apparatus for dispensing low nanoliter volumes of liquid while minimizing waste
DE10046379A1 (en) * 2000-09-20 2002-03-28 Zeiss Carl System for the targeted deformation of optical elements
US6875402B2 (en) * 2000-10-16 2005-04-05 Ngk Insulators, Ltd. Micropipette, dispenser and method for producing biochip
US20020106308A1 (en) * 2001-02-02 2002-08-08 Zweifel Ronald A. Microdrop dispensing apparatus
DE10106605A1 (en) * 2001-02-13 2002-08-22 Zeiss Carl System for eliminating or at least damping vibrations
US6480114B2 (en) * 2001-03-23 2002-11-12 Nordson Corporation High impedance diagnostic for gun driver and method
US7670429B2 (en) 2001-04-05 2010-03-02 The California Institute Of Technology High throughput screening of crystallization of materials
DE10132530A1 (en) * 2001-07-09 2003-01-30 Evotec Ag Method for monitoring the functionality of a liquid delivery device and liquid delivery device
DE10136387A1 (en) * 2001-07-26 2003-02-13 Zeiss Carl Optical objective for semiconductor lithography has optical element with reflective reference surface used for adjustment relative to objective
US20030095167A1 (en) * 2001-11-16 2003-05-22 Jameson Lee Kirby Apparatus and method to produce topography, unique fluid handling properties and bonding properties on and within substrates
US7288228B2 (en) * 2002-02-12 2007-10-30 Gilson, Inc. Sample injection system
US6782928B2 (en) 2002-03-15 2004-08-31 Lg.Philips Lcd Co., Ltd. Liquid crystal dispensing apparatus having confirming function for remaining amount of liquid crystal and method for measuring the same
DE10219514A1 (en) 2002-04-30 2003-11-13 Zeiss Carl Smt Ag Lighting system, especially for EUV lithography
EP1364710B1 (en) * 2002-05-13 2009-10-07 Becton, Dickinson and Company Self-aliquoting sample storage plate
US6874699B2 (en) * 2002-10-15 2005-04-05 Wisconsin Alumni Research Foundation Methods and apparata for precisely dispensing microvolumes of fluids
WO2004065011A1 (en) * 2003-01-23 2004-08-05 Evotec Oai Ag Method for filling sample carriers
US7258253B2 (en) * 2003-04-30 2007-08-21 Aurora Discovery, Inc. Method and system for precise dispensation of a liquid
US20050074827A1 (en) * 2003-07-18 2005-04-07 Ute Muh Methods for identifying modulators of quorum-sensing signaling in bacteria
US20060272738A1 (en) * 2003-09-19 2006-12-07 Gary Lim High density plate filler
US7407630B2 (en) * 2003-09-19 2008-08-05 Applera Corporation High density plate filler
US8277760B2 (en) * 2003-09-19 2012-10-02 Applied Biosystems, Llc High density plate filler
US20050233472A1 (en) * 2003-09-19 2005-10-20 Kao H P Spotting high density plate using a banded format
US7998435B2 (en) * 2003-09-19 2011-08-16 Life Technologies Corporation High density plate filler
US20070014694A1 (en) * 2003-09-19 2007-01-18 Beard Nigel P High density plate filler
US20050226782A1 (en) * 2003-09-19 2005-10-13 Reed Mark T High density plate filler
US20060233671A1 (en) * 2003-09-19 2006-10-19 Beard Nigel P High density plate filler
US20050232821A1 (en) * 2003-09-19 2005-10-20 Carrillo Albert L High density plate filler
US20050226771A1 (en) * 2003-09-19 2005-10-13 Lehto Dennis A High speed microplate transfer
US20050220675A1 (en) * 2003-09-19 2005-10-06 Reed Mark T High density plate filler
US20060233673A1 (en) * 2003-09-19 2006-10-19 Beard Nigel P High density plate filler
US20050163637A1 (en) * 2003-12-04 2005-07-28 Irm, Llc Material conveying systems, computer program products, and methods
US7265917B2 (en) * 2003-12-23 2007-09-04 Carl Zeiss Smt Ag Replacement apparatus for an optical element
EP1604741A1 (en) * 2004-05-14 2005-12-14 F. Hoffmann-La Roche Ag Method and apparatus for dispensing a liquid with a pipetting needle
EP1614469B1 (en) * 2004-05-14 2007-09-19 F. Hoffmann-La Roche Ag Method and apparatus for dispensing a liquid with a pipetting needle
FR2879482B1 (en) * 2004-12-20 2007-03-30 Oreal DEVICE FOR SPRAYING A PRODUCT, IN PARTICULAR A FRAGRANCE
WO2006070353A2 (en) * 2004-12-30 2006-07-06 Safend Ltd Method and system for securely identifying computer storage devices
DE102005025640A1 (en) * 2005-06-03 2006-12-07 Scienion Ag Microdispenser and associated operating method
EP2098588B1 (en) * 2006-11-22 2013-01-02 Altair Corporation Pipette core member, pipette, and pipette device
WO2008077002A2 (en) * 2006-12-18 2008-06-26 Avon Products, Inc. Self-contained voltage generating systems
FR2910254B1 (en) * 2006-12-20 2009-04-17 Oreal PIEZOELECTRIC SPRAY SYSTEM AND CORRESPONDING REFILL
FR2910253B1 (en) * 2006-12-20 2010-03-12 Oreal METHOD FOR DISPENSING A PRODUCT SPRAYED BY A PIEZOELECTRIC SPRAY SYSTEM AND A SPRAY SYSTEM FOR IMPLEMENTING SUCH A METHOD
DE102008000967B4 (en) 2008-04-03 2015-04-09 Carl Zeiss Smt Gmbh Projection exposure machine for EUV microlithography
JP5746973B2 (en) 2008-12-05 2015-07-08 フルイセンス アーペーエス Body fluid sampling device and method
US20130206857A1 (en) * 2011-01-21 2013-08-15 Biodot, Inc. Piezoelectric dispenser with a longitudinal transducer and replaceable capillary tube
US10684303B2 (en) 2011-07-22 2020-06-16 Vanrx Pharmasystems Inc. Method for protecting and unprotecting the fluid path in a controlled environment enclosure
ITMI20121803A1 (en) * 2012-10-24 2014-04-25 Altergon Sa METHOD AND MEASUREMENT AND CONTROL DEVICE FOR THE DOSAGE OF SMALL QUANTITIES OF FLUID BY MEANS OF NEEDLE RESONANT, AND NEEDLE RESONANT SUITABLE FOR THE PURPOSE
JP7154192B2 (en) * 2019-06-27 2022-10-17 京セラ株式会社 pipette
CN110787851B (en) * 2019-10-25 2020-12-04 浙江大学 Multi-channel liquid drop quantitative measuring device and method based on pressure driving
TW202315462A (en) * 2021-06-10 2023-04-01 荷蘭商Asml荷蘭公司 Target supply apparatus

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4199770A (en) * 1978-12-04 1980-04-22 Xerox Corporation Coincidence gate ink jet with increased operating pressure window
US4228440A (en) * 1977-12-22 1980-10-14 Ricoh Company, Ltd. Ink jet printing apparatus
US4231047A (en) * 1978-06-07 1980-10-28 Ricoh Co., Ltd. Ink-jet printing method and device therefor
US4395719A (en) * 1981-01-05 1983-07-26 Exxon Research And Engineering Co. Ink jet apparatus with a flexible piezoelectric member and method of operating same
US4499479A (en) * 1982-08-30 1985-02-12 International Business Machines Corporation Gray scale printing with ink jet drop-on demand printing head
US4822250A (en) * 1986-03-24 1989-04-18 Hitachi, Ltd. Apparatus for transferring small amount of fluid

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3946398A (en) * 1970-06-29 1976-03-23 Silonics, Inc. Method and apparatus for recording with writing fluids and drop projection means therefor
US3683212A (en) * 1970-09-09 1972-08-08 Clevite Corp Pulsed droplet ejecting system
US3832579A (en) 1973-02-07 1974-08-27 Gould Inc Pulsed droplet ejecting system
US4032929A (en) * 1975-10-28 1977-06-28 Xerox Corporation High density linear array ink jet assembly
DE2555749C3 (en) * 1975-12-11 1980-09-11 Olympia Werke Ag, 2940 Wilhelmshaven Device for damping the backflow of the ink in the nozzle of an ink jet head
DE2756134A1 (en) * 1977-12-16 1979-06-21 Ibm Deutschland PIEZOELECTRICALLY CONTROLLED DRIVE ARRANGEMENT FOR THE GENERATION OF HIGH SHOCK SPEEDS AND / OR CONTROLLED STROKE
US4308546A (en) * 1978-03-15 1981-12-29 Gould Inc. Ink jet tip assembly
JPH0234780B2 (en) 1978-11-13 1990-08-06 Canon Kk KIROKUHOHO
US4233610A (en) 1979-06-18 1980-11-11 Xerox Corporation Hydrodynamically damped pressure pulse droplet ejector
JPS5729463A (en) 1980-07-30 1982-02-17 Nec Corp Liquid jet head
US4354197A (en) * 1980-10-03 1982-10-12 Ncr Corporation Ink jet printer drive means
DE3170016D1 (en) * 1980-10-15 1985-05-23 Hitachi Ltd Ink jet printing apparatus
JPS57144767A (en) 1981-03-04 1982-09-07 Toshiba Corp Pressure pulse type ink jet recording device
NL8102227A (en) 1981-05-07 1982-12-01 Philips Nv METHOD FOR MANUFACTURING JET PIPES AND INK PRINT WITH A JET PIPE MANUFACTURED BY THAT PROCESS.
US4418356A (en) * 1981-09-23 1983-11-29 Ncr Corporation Ink jet print head
US4520374A (en) * 1981-10-07 1985-05-28 Epson Corporation Ink jet printing apparatus
US4523199A (en) * 1982-09-29 1985-06-11 Exxon Research & Engineering Co. High stability demand ink jet apparatus and method of operating same
IT1157118B (en) 1982-12-03 1987-02-11 Olivetti & Co Spa INK JET PRINTER DEVICE
DE3341401A1 (en) * 1983-11-15 1985-05-23 Siemens AG, 1000 Berlin und 8000 München METHOD AND CONVERTER FOR INCREASING RESOLUTION IN AN INK MOSAIC WRITER
JPS61106259A (en) * 1984-10-31 1986-05-24 Hitachi Ltd Ink droplet jet discharging device
US4550325A (en) * 1984-12-26 1985-10-29 Polaroid Corporation Drop dispensing device
US4605939A (en) * 1985-08-30 1986-08-12 Pitney Bowes Inc. Ink jet array
US4752788A (en) 1985-09-06 1988-06-21 Fuji Electric Co., Ltd. Ink jet recording head
US4877745A (en) 1986-11-17 1989-10-31 Abbott Laboratories Apparatus and process for reagent fluid dispensing and printing
US4992808A (en) 1987-01-10 1991-02-12 Xaar Limited Multi-channel array, pulsed droplet deposition apparatus
US4887100A (en) 1987-01-10 1989-12-12 Am International, Inc. Droplet deposition apparatus
JPS63283739A (en) * 1987-05-14 1988-11-21 Agency Of Ind Science & Technol Small amount takeoff device for fine powder-viscous fluid or the like
JPH02293040A (en) * 1989-05-08 1990-12-04 Misuzu Erii:Kk Quantitatively force-feeding method for fluid
GB2265113B (en) 1992-02-25 1996-05-01 Citizen Watch Co Ltd Ink jet head
JPH06218917A (en) * 1993-01-22 1994-08-09 Sharp Corp Ink jet head
US5958342A (en) 1996-05-17 1999-09-28 Incyte Pharmaceuticals, Inc. Jet droplet device
ATE259068T1 (en) * 1996-05-31 2004-02-15 Packard Instrument Co Inc DEVICE FOR HANDLING MICROLIQUID QUANTITIES
US5961298A (en) * 1996-06-25 1999-10-05 California Institute Of Technology Traveling wave pump employing electroactive actuators
JP3271540B2 (en) * 1997-02-06 2002-04-02 ミノルタ株式会社 Ink jet recording device
US6232129B1 (en) * 1999-02-03 2001-05-15 Peter Wiktor Piezoelectric pipetting device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4228440A (en) * 1977-12-22 1980-10-14 Ricoh Company, Ltd. Ink jet printing apparatus
US4231047A (en) * 1978-06-07 1980-10-28 Ricoh Co., Ltd. Ink-jet printing method and device therefor
US4199770A (en) * 1978-12-04 1980-04-22 Xerox Corporation Coincidence gate ink jet with increased operating pressure window
US4395719A (en) * 1981-01-05 1983-07-26 Exxon Research And Engineering Co. Ink jet apparatus with a flexible piezoelectric member and method of operating same
US4499479A (en) * 1982-08-30 1985-02-12 International Business Machines Corporation Gray scale printing with ink jet drop-on demand printing head
US4822250A (en) * 1986-03-24 1989-04-18 Hitachi, Ltd. Apparatus for transferring small amount of fluid

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6599479B1 (en) * 1997-12-05 2003-07-29 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Device and procedure for the electrically triggered microdrop release with a dispensing head
US7427379B1 (en) * 1999-03-19 2008-09-23 Biotage Ab Liquid dispensing apparatus
US7497995B2 (en) 2000-10-11 2009-03-03 Innovadyne Technologies, Inc. Hybrid valve apparatus and method for fluid handling
US7135146B2 (en) 2000-10-11 2006-11-14 Innovadyne Technologies, Inc. Universal non-contact dispense peripheral apparatus and method for a primary liquid handling device
US20040050861A1 (en) * 2000-10-24 2004-03-18 Thomas Lisec Pipette system and pipette array
US7413710B2 (en) * 2000-10-24 2008-08-19 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Pipette system and pipette array
US20020106812A1 (en) * 2001-01-26 2002-08-08 Fisher William D. Fluid drop dispensing
WO2002070133A1 (en) * 2001-03-01 2002-09-12 Peter Wiktor Piezoelectric pipetting device housing and methods for making and using the same
US6983636B2 (en) * 2002-01-25 2006-01-10 Innovadyne Technologies, Inc. Apparatus and method for assessing the liquid flow performances through a small dispensing orifice
US20030167822A1 (en) * 2002-01-25 2003-09-11 Innovadyne Technologies, Inc. Univeral calibration system and method for a high performance, low volume, non-contact liquid dispensing apparatus
US10253361B2 (en) 2002-07-30 2019-04-09 Applied Biosystems, Llc Sample block apparatus and method for maintaining a microcard on a sample block
US20060057740A1 (en) * 2002-12-02 2006-03-16 Arkray Method for manufacturing tool for analysis
US20070015289A1 (en) * 2003-09-19 2007-01-18 Kao H P Dispenser array spotting
US20100086977A1 (en) * 2003-09-19 2010-04-08 Life Technologies Corporation Pressure Chamber Clamp Mechanism
US8906325B2 (en) 2003-09-19 2014-12-09 Applied Biosystems, Llc Vacuum assist for a microplate
US9213042B2 (en) 2003-09-19 2015-12-15 Applied Biosystems, Llc Vacuum assist for a microplate
US20050226779A1 (en) * 2003-09-19 2005-10-13 Oldham Mark F Vacuum assist for a microplate
US20120304929A1 (en) * 2011-01-21 2012-12-06 Biodot, Inc. Piezoelectric dispenser with a longitudinal transducer and replaceable capillary tube
US9068566B2 (en) * 2011-01-21 2015-06-30 Biodot, Inc. Piezoelectric dispenser with a longitudinal transducer and replaceable capillary tube

Also Published As

Publication number Publication date
EP1137489B1 (en) 2003-07-09
EP1316361A3 (en) 2004-03-31
ATE354440T1 (en) 2007-03-15
EP1316361A2 (en) 2003-06-04
CA2354555C (en) 2008-08-12
ATE244604T1 (en) 2003-07-15
DK1137489T3 (en) 2003-10-20
US20050032242A1 (en) 2005-02-10
WO2000033961A1 (en) 2000-06-15
EP1137489A1 (en) 2001-10-04
AU3118900A (en) 2000-06-26
JP2002531259A (en) 2002-09-24
ES2284995T3 (en) 2007-11-16
ES2201823T3 (en) 2004-03-16
DE69909511D1 (en) 2003-08-14
DE69935262D1 (en) 2007-04-05
EP1316361B1 (en) 2007-02-21
DE69909511T2 (en) 2004-04-15
PT1137489E (en) 2003-10-31
CA2354555A1 (en) 2000-06-15
US6296811B1 (en) 2001-10-02
DE69935262T2 (en) 2007-11-15

Similar Documents

Publication Publication Date Title
US6296811B1 (en) Fluid dispenser and dispensing methods
JP4028716B2 (en) Multiple ejector system for dispensing biofluids
US6808683B2 (en) Droplet dispensing system
US7160511B2 (en) Liquid pipetting apparatus and micro array manufacturing apparatus
US7900850B2 (en) Microdosing apparatus and method for dosed dispensing of liquids
US7467751B2 (en) Methods and apparata for precisely dispensing microvolumes of fluids
US20020168297A1 (en) Method and device for dispensing of droplets
CA2404735C (en) A device for dispensing accurately-controlled small doses of liquid
JP3713017B2 (en) Apparatus and method for supplying microdroplets on a substrate in a non-contact manner
JP3598066B2 (en) Fluid control device with format conversion function
US20060171854A1 (en) Pipette tip, pipetting device, pipette tip actuating device and method for pipetting in the NL range
JP2008249720A (en) Droplet dispensing system
JP2004513376A (en) Apparatus and system for dispensing or aspirating / dispensing a liquid sample
JP4024523B2 (en) Inspection method for multiple ejector systems
WO2002092228A2 (en) A method and device for dispensing of droplets
WO2003054553A1 (en) Generic array dispenser with laminar virtual flow channels
IE20020333A1 (en) A method and device for dispensing of droplets
JP2005062022A (en) Dispensing device and dispensing method

Legal Events

Date Code Title Description
AS Assignment

Owner name: AURORA BIOSCIENCES CORPORATION, CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SASAKI, GLENN C.;REEL/FRAME:012105/0347

Effective date: 19990128

AS Assignment

Owner name: VERTEX PHARMACEUTICALS (SAN DIEGO) LLC, CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:AURORA BIOSCIENCES CORPORATION;REEL/FRAME:013056/0630

Effective date: 20020528

AS Assignment

Owner name: AURORA DISCOVERY, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:VERTEX PHARMACEUTICALS (SAN DIEGO) LLC;REEL/FRAME:014196/0860

Effective date: 20031203

AS Assignment

Owner name: OXFORD FINANCE CORPORATION, VIRGINIA

Free format text: SECURITY AGREEMENT;ASSIGNOR:AURORA DISCOVERY, INC.;REEL/FRAME:015056/0495

Effective date: 20040806

AS Assignment

Owner name: AURORA DISCOVERY, INC., CALIFORNIA

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:OXFORD FINANCE CORPORATION;REEL/FRAME:017492/0559

Effective date: 20060420

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: BECKMAN COULTER, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:AURORA DISCOVERY, INC.;REEL/FRAME:020976/0834

Effective date: 20060930

AS Assignment

Owner name: AURORA DISCOVERY, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:VERTEX PHARMACEUTICALS (SAN DIEGO) LLC;REEL/FRAME:020995/0110

Effective date: 20031203

Owner name: VERTEX PHARMACEUTICALS (SAN DIEGO) LLC, CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:AURORA BIOSCIENCES CORPORATION;REEL/FRAME:020995/0096

Effective date: 20020701