Microvolume liquid handling system

• US 6,592,825 B2
• Filed: 02/01/2001
• Issued: 07/15/2003
• Est. Priority Date: 05/31/1996
• Status: Expired due to Term

• Current Assignee: Packard Instrument Co., Inc. (Revvity, Inc.)
• Original Assignee: Packard Instrument Co., Inc. (Revvity, Inc.)
• Inventors: Meyer, Wilhelm, Chibucos, Nicholas S., Pelc, Richard E., Papen, Roeland F.
• Primary Examiner(s): Ludlow, Jan M
• Application Number:
  US09/775,276
• Publication Number:
  US 20010016177A1
• Time in Patent Office: 894 Days
• Field of Search: 222/57, 222/333, 422/100, 436/49, 436/54, 436/180, 738/641.1
• US Class Current: 422/521
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01L 3/0265 using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01F 1/48 the pressure or differential pressure being created by a capillary element
• CPC Class Codes: G01F 3/00 Measuring the volume flow of fluids or fluent solid material wherein the fluid passes through the meter in successive and more or less isolated quantities, the meter being driven by the flow measuring a proportion of the volume flow G01F5/00
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/1018 Detecting inhomogeneities, e.g. foam, bubbles, clots
• CPC Class Codes: G01N 2035/1025 Fluid level sensing
• CPC Class Codes: G01N 2035/1039 Micropipettes, e.g. microcapillary tubes
• CPC Class Codes: G01N 2035/1041 Ink-jet like dispensers
• CPC Class Codes: G01N 35/1065 Multiple transfer devices
• CPC Class Codes: Y10T 436/114998 with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/119163 with aspirator of claimed structure
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A microvolume liquid handling system includes a microdispenser employing a piezoelectric transducer attached to a glass capillary, a positive displacement pump for priming and aspirating transfer liquid into the microdispenser, controlling the pressure of the liquid system, and washing the microdispenser between liquid transfers, and a pressure sensor to measure the liquid system pressure and produce a corresponding electrical signal. Dispensing of a single sub-nanoliter drop can be detected in real time. As the result of dispensing the liquid in sub-nanoliter droplets, the dispensed volume can be precisely controlled. The dispenser automatically detects the liquid surface of the transfer liquid, automatically aspirate, analyze desired volume of the transfer liquid, dispense the transfer liquid without contacting the destination vessel or its contents, and automatically wash off the transfer liquid from dispensing system after each transfer. This system is capable of automatically sensing liquid surfaces, aspirating liquid to be transferred, and then dispensing small quantities of liquid with high accuracy, speed and precision. The system is pulsated at high frequency to prevent or eliminate clogging. Immiscible liquid between the transfer liquid and the system liquid reduces the required amount of transfer liquid needed for dispensing.

Claims

1. A microvolume liquid handling system for dispensing small quantities of liquids, comprising:

pumping means for controlling the pressure and flow of a first liquid;

microdispenser means for dispensing microvolumes of a second liquid, said first liquid and said second liquid separated by a compressible fluid;

a sensor for converting pressure changes in at least one of said first liquid and said second liquid into a signal;

tubing means for connecting said pumping means to said sensor and said sensor to said microdispenser means; and

means for converting the signal into an indication of fluid volume dispensed;

vibrating means for vibrating said microdispenser means at a frequency sufficiently high to dislodge foreign material adhering to said microdispenser.

2. The microvolume liquid handling system of claim 1 wherein said vibrating means further comprises a piezoelectric transducer.

3. The microvolume liquid handling system of claim 1 wherein said frequency is a high frequency.

4. The microvolume liquid handling system of claim 3 wherein said frequency is approximately a resonant ultrasonic frequency of said microdispenser means.

5. The microvolume liquid handling system of claim 4 wherein said resonant frequency is approximately 12 kHz.

6. The microvolume liquid handling system of claim 1 wherein said pressure sensor contains a piezoresistive element capable of converting pressure into an electrical signal.

7. The microvolume liquid handling system of claim 1 wherein said tubing means further comprises teflon.

8. The microvolume liquid handling system of claim 1 wherein said means for dispensing further comprise a capillary and a piezoelectric transducer in substantially radial contact with a portion of said capillary.

9. The microvolume liquid handling system of claim 1 wherein said microdispenser is mounted on a robotic system capable of moving said microdispenser.

10. The microvolume liquid handling system of claim 1 wherein said robotic system is a three-axis system.