Microdosing device

Pumps – Processes

Reexamination Certificate

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C417S413300

Reexamination Certificate

active

06416294

ABSTRACT:

PRIORITY
Applicants claim the benefit of priority from International Application PCT/EP99/00185.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a microdosing device.
2. Description of Prior Art
Precise dosing of extremely small volumes of fluid in the range between 0.01 &mgr;l and 1 &mgr;l is of great and decisive importance e.g. in the fields of biotechnology, DNA analytical chemistry and combinatorial chemistry. According to the prior art, dispensers or pipettes are predominantly used for dosing small volumes. In these cases, the volume to be dosed is displaced either directly, by a so-called piston-type direct displacement, or via an intermediate air cushion. In this respect, reference is made e.g. to the article “Pipettieren und Dispensieren”, A. Jahns, Fachzeit-schrift der Technischen Assistenten in der Medizin, volume 8 (1993), No. 12, pages 116-1172, Umschau Zeitschriftenver-lag.
Air-cushion pipettes are suitable for dosing volumes between 0.01 &mgr;l and 5 ml, accuracies of ±2-3% being achieved in the case of volumes exceeding 1 &mgr;l. In the case of smaller volumes, however, the accuracies achieved are only accuracies of approx. ±10% due to surface effects at the tip of the pipette. The limited dosing accuracy in the case of smaller volumes is predominantly due to the fact that the tip of the pipette or dispenser must be immersed into the medium to be dosed, whereby the dosing amount will be influenced by effects such as surface tension, wetting and hydrostatic pressure. In order to avoid these problems as well as the risk of carrying over media due to immersion, a dosing system should be based on the discharge of the dosed volume in a free jet. Direct-diplacement dispensing devices offer this additional advantage, but only in the case of volumes of approx. 10 &mgr;l and more.
Known systems discharging extremely small volumes of fluid in a free jet are ink-jet printheads. Ink-jet printheads are known which are based on two fundamentally different principles, viz. those which are effective making use of thermal transducers and those which are effective making use of piezoelectric transducers. In this respect, reference is made to the publications N. Schwesinger: “Planarer Tinten-strahldruckkopf”. F&M, 11-12; pages 456-460; 1993; H. Bentin, M. Doering, W. Radtke, U. Rothgordt: “Physical Properties of Micro-Planar Ink-Drop Generators”. J. Imaging Technology, 3; pages 152-155; 1986; and Wolfgang Wehl; Tinten-drucktechnologie; Paradigma und Motor der Mikrosystemtechnik; Feinwerktechnik & MeBtechnik; part 1 in edition 6/95, part 2 in edition 9/95.
In the case of printheads operating according to the “drop-on-demand” principle, a small ink drop is flung in a free jet onto a paper after the application of a voltage pulse. A typical drop diameter is approx. 60 &mgr;m, i.e. the volume is approx. 0.0001 &mgr;l. Normally, these printheads are, however, only adapted to be used in combination with special inks. Media which are used e.g. in the field of biotechnology are in most cases very different from these inks as far as viscosity and surface tension are concerned. However, the viscosity and the surface tension substantially influence the size of the drops and, consequently, the volume dosed. Furthermore, a generation of drops is only possible in a very limited viscosity range. The volume of the individual drops can, moreover, only be modified in a very limited range by modifying the control pulses.
Furthermore, dosing systems are known, which are also capable of generating drops in the case of media having strongly different viscosities. Such a system is described e.g. in the publication “Mikrodosierung”, company publication of the firm of microdrop GmbH, Norderstedt, 1995. As in the case of ink-jet printheads, the drop volume is here determined predominantly by the size of the nozzle diameter. only to a very limited extent can it also be influenced by the electric control of the actuator. As in the case of ink-jet printheads, the process of drop tearing at the nozzle depends, however, on the physical properties of the media to be dosed, i.e. on the viscosity, the surface tension, etc. The exact size of the drops is therefore again strongly media-dependent. The dosing of a desired volume, which lies in the range between 0.1 &mgr;p and 1 &mgr;l in most cases, is based the counting of individual drops of the same size. The typical volume of an individual drop is smaller than 0.001 &mgr;l. Since the volume errors of the individual drops will, however, accumulate in this process, the dosing accuracy is strongly limited.
An increase of this dosing accuracy is only possible with the aid of complicated and expensive systems. An image processing system can, for example, be used by means of which the size of the individual drops can be determined and the number of drops required can be calculated during a dosing process. Furthermore, according to an alternative method of increasing the dosing accuracy, a fluorescent substance can be admixed to the medium to be dosed. In the case of this alternative method, the dosing process will be finished when the intensity of the fluorescent signal reaches the set value. It is, however, easily evident that the above-mentioned methods of increasing the dosing accuracy are both very complicated and expensive.
EP-A-0439327 discloses a control system for a micropump, which is adapted to be used e.g. in a dosing device. The control system selectively controls the generation of drive pulses so as to control the discharge of fluid through the pump. This known control for a micropump uses respective square-wave signals having different amplitudes so as to control a piezoelectric driver element which serves to drive a pump membrane.
EP-A-0725267 discloses an electrically controllable micropipette for handling extremely small fluid volumes in the range of a few hundred pl to a few &mgr;l. The main component of this known micropipette is a micromembrane pump operated as a microejection pump; a second micromembrane pump can additionally be provided, which is implemented as a micropressure or a microsuction pump. Each of these respective pumps is controlled by square-wave voltages.
In the prior, non-prepublished German application 19706513.9-52 owned by the applicant of the present application and filed on Feb. 19, 1997, a microdosing device is disclosed, which permits a discharge of exactly defined volumes of fluid. This application discloses a microdosing device comprising a pressure chamber which is at least partly delimited by a displacer. An actuating device for actuating the displacer is provided, the volume of the pressure chamber being adapted to be changed by actuating the displacer. A media reservoir is in fluid comunication with the pressure chamber via a first fluid line, whereas an outlet opening is in fluid communication with the pressure chamber via a second fluid line. For causing a defined fluid volume to be discharged from the outlet opening, the above-mentioned publication discloses that there are provided a means for detecting the respective position of the displacer and a control means which is connected to the actuating device and to the means for detecting the position of the displacer, the control means controlling the actuating device on the basis of the detected position of the displacer or on the basis of displacer positions detected during at least one preceding dosing cycle.
By means of the microdosing device disclosed in the above-mentioned German application 19706513.9-52 it is possible to eject exactly defined volumes of fluid independently of the vicosity of the fluid to be dosed by controlling the actuator of the displacer on the basis of the output signals of the volume sensor. It follows that the defined fluid volume is almost independent of the viscosity, surface tensions, etc. of the medium to be dosed. It follows that media which differ with regard to viscosity and surface tensions can be dosed according to the above-mentioned German application, such media being used

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