Method and device for metering liquids

• US 5,856,200 A
• Filed: 04/18/1996
• Issued: 01/05/1999
• Est. Priority Date: 09/08/1993
• Status: Expired due to Fees

• Current Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Original Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Inventors: Klose, Sigmar, Krause, Friedemann
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US08/634,366
• Time in Patent Office: 992 Days
• Field of Search: 436/5, 436/51, 436/164, 436/180, 422/82.05, 356/335, 356/336
• US Class Current: 436/180
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: G01F 1/661 using light
• CPC Class Codes: G01F 22/00 Methods or apparatus for measuring volume of fluids or fluent solid material, not otherwise provided for
• 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 2035/1037 Using surface tension, e.g. pins or wires
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

The present invention relates to a method and a device for metering liquids, wherein the volume of a droplet of a sample liquid is determined by means of optical measuring. The liquid to be metered is brought into contact with a transfer element so that a droplet adheres to the transfer element. The transfer element and the liquid adhering thereto are illuminated from one or several directions and the resulting images are displayed on an optical sensor. The liquid volume is determined on the basis of these images. Metering is accomplished by transferring the liquid volume adhering to the transfer element into an analysis vessel.

Claims

1. A method of metering a liquid to be used in an analysis, said method comprising the steps of:

a) contacting a transfer element with the liquid to cause a droplet of the liquid to adhere to and cover an end of the transfer element;

b) illuminating the droplet and at least a part of the transfer element to produce at least one picture of the droplet and of a part of the transfer element on an optical sensor;

c) determining the contours of the droplet on the transfer element from the at least one picture produced on the optical sensor, and calculating the volume of the droplet from the determined contours; and

d) transferring the droplet adhering to the transfer element to an analysis vessel,

wherein the transfer element is a solid rod-like body having at least one front side and one circumferential surface, and wherein the droplet adheres to the front side of the transfer element.

2. Method of claim 1, wherein the droplet and at least a part of the transfer element are illuminated in at least two spatial, non parallel directions to produce at least two images of the droplet and a part of the transfer element, which at least two images are used to calculate the volume of the droplet.

3. Method according to claim 1, wherein the volume of the droplet is between 10 and 500 nl.

4. Method of claim 1, including the step of recording the at least one image of the droplet and a part of the transfer element with a CCD-camera.

5. Method of claim 1, wherein the droplet and at least a part of the transfer element are illuminated by a light source, with the optical path between the light source and the optical sensor being modified by the use of lenses, mirrors and diaphragms.

6. Method of claim 1, wherein the sample volume is between 400 nl and 1 μ

l, and the production of a picture of the droplet and the part of the transfer element on the optical sensor is within 3 to 5 seconds after the contact step.

7. Method of claim 1, wherein the droplet is illuminated from a light source, and the method includes the additional steps of splitting the light from the light source by means of a beam splitter, and redirecting the light on the droplet from different spatial directions.

8. Method of claim 1, wherein the contours of the droplet and a part of the transfer element are determined from the at least one image with the aid of a spline function using the diffraction pattern.

9. Method of claim 1, wherein the optical sensor has a given light sensitivity level, and the droplet and at least a part of the transfer element are illuminated with light of a brightness which is at least 10-fold greater than the light sensitivity level.

10. A method of metering a liquid as recited in claim 1, said method comprising initial steps of:

illuminating the transfer element to produce at least one picture of a part of the transfer element on an optical sensor, and determining contours of the part of the transfer element from the at least one picture.

11. Method according to claim 1, wherein the rod-like transfer element has a circumferential surface to which the liquid essentially does not adhere, and a front side to which the liquid does adhere.

12. A method according to claim 11, wherein said circumferential surface is hydrophobic and wherein said front side is hydrophilic.

13. Method of claim 1, wherein the contours of the droplet and a part of the transfer element are determined from the at least one image by the use of a brightness cut-off value.

14. Method of claim 13, wherein the brightness cut off value is approximately 25 percent of a reference brightness which is the maximum brightness of a light source illuminating the droplet and at least a part of the transfer element.

15. A method of metering a liquid to be used in an analysis, said method comprising the steps of:

a) contacting a liquid impermeable transfer element with the liquid to cause a droplet of the liquid to adhere to the transfer element;

b) illuminating the droplet and at least a part of the transfer element to produce at least one picture of the droplet and of a part of the transfer element on an optical sensor;

c) determining the contours of the droplet on the transfer element from the at least one picture produced on the optical sensor, and calculating the volume of the droplet from the determined contours; and

d) transferring the droplet adhering to the transfer element to an analysis vessel, wherein the transfer element is a planar surface element of a size which is greater than the diameter of the droplet.

16. Method of claim 15, wherein the wetting angle formed between the droplet and the planar surface element of the transfer element is greater than 90°

.

17. A method of metering a liquid as recited in claim 15, said method comprising initial steps of:

illuminating the transfer element to produce at least one picture of a part of the transfer element on an optical sensor, and determining contours of the part of the transfer element from the at least one picture.

18. A method according to claim 15, wherein said step of illuminating the droplet and at least a part of the transfer element includes irradiation of light through a light-permeable part of the transfer element.

19. A system for metering liquids comprising:

a) a transfer element to which at least one droplet of liquid adheres due to adhesive and/or gravitational forces, said transfer element comprising a solid rod-like body;

b) an illumination unit including at least one light source, for illuminating the droplet and at least part of the transfer element;

c) adjusting means for supporting the transfer element and for allowing movement of the transfer element in at least one spatial direction within a light path of the illumination unit;

d) detecting means for detecting light after the light has passed the transfer element, and for producing at least one picture of the droplet and a part of the transfer element;

e) evaluation means for determining the contours of the at least one droplet of liquid with the aid of signals from the detection means, and for calculating from the contours so determined the volume of the at least one droplet of liquid; and

f) transfer means for transferring the element with at least one droplet of liquid thereon to an analysis vessel.

20. System of claim 19, wherein the illumination unit has at least two bundles of beams illuminating in non-parallel spatial directions the at least one droplet adhering to the transfer element.

21. System of claim 19, wherein the detection means is a CCD-camera equipped with a system including lenses, mirrors and diaphragms.

22. System of claim 19, wherein the adjusting means positions the least one droplet of liquid in the focus of a lens system, and projects at least one image of the at least one droplet of liquid on an optical sensor.

23. System of claim 19, wherein the detecting means has a given level of sensitivity to light, and the illumination source illuminates the transfer element with light having a brightness which is at least 10-fold greater than the said light sensitivity level.

24. System of claim 19, wherein the evaluation means uses threshold value procedures or spline function procedures based on the signals of the detection means to determine the contours of the at least one droplet of liquid, which then permit the calculation of the volume of said at least one droplet of liquid.

25. System of claim 24, wherein the evaluation means uses threshold value procedures based on a brightness cut-off value, and the brightness cut-off value is approximately 25% of a reference brightness which is the maximum brightness of the light source.

26. A system for metering liquids comprising:

a) a transfer element to which at least one droplet of liquid adheres due to adhesive and/or gravitational forces, wherein the transfer element has a planar surface element which is of a size greater than the diameter of the droplet;

b) an illumination unit including at least one light source, for illuminating the droplet and at least part of the transfer element;

c) adjusting means for supporting the transfer element and for allowing movement of the transfer element in at least one spatial direction within a light path of the illumination unit;

d) detecting means for detecting light after the light has passed the transfer element, and for producing at least one picture of the droplet and a part of the transfer element;

e) evaluation means for determining the contours of the at least one droplet of liquid with the aid of signals from the detection means, and for calculating from the contours so determined the volume of the at least one droplet of liquid; and

f) transfer means for transferring the element with at least one droplet of liquid thereon to an analysis vessel.

27. A method of determining the volume of a droplet of a liquid, said method comprising:

a) contacting a transfer element with the liquid to cause a droplet of the liquid to adhere to and cover an end of the transfer element,

b) illuminating the droplet and at least a part of the transfer element to produce at least one picture of the droplet and of a part of the transfer element on an optical sensor,

c) determining the contours of the droplet from the at least one picture produced on the optical sensor, and calculating the volume of the droplet from the so determined contours,

wherein said transfer element comprising a solid rod-like body having at least one front side and one circumferential surface, and wherein the droplet adheres to the front side of the transfer element.

28. A method of metering a liquid to be used in an analysis, said method comprising the steps of:

a) contacting a transfer element with the liquid to cause a droplet of the liquid to adhere to the transfer element, wherein said transfer element is formed such that the liquid does not penetrate the transfer element;

b) illuminating the droplet and at least a part of the transfer element to produce at least one picture of the droplet and of a part of the transfer element on an optical sensor;

c) determining the contours of the droplet on the transfer element from the at least one picture produced on the optical sensor, and calculating the volume of the droplet from the determined contours; and

d) transferring the droplet adhering to the transfer element to an analysis vessel,

wherein the transfer element is a solid rod-like body having at least one end and one circumferential surface, and wherein the droplet adheres to and covers the at least one end of the transfer element.

29. A method according to claim 28, wherein said step of illuminating the droplet and at least a part of the transfer element includes irradiation of light through a light-permeable part of the transfer element.

30. A method of metering a liquid to be used in an analysis, said method comprising the steps of:

a) contacting a transfer element with the liquid to cause a droplet of the liquid to adhere to the transfer element, wherein said transfer element is formed such that the liquid does not penetrate the transfer element;

b) illuminating the droplet and at least a part of the transfer element to produce at least one picture of the droplet and of a part of the transfer element on an optical sensor;

c) determining the contours of the droplet on the transfer element from the at least one picture produced on the optical sensor, and calculating the volume of the droplet from the determined contours; and

d) transferring the droplet adhering to the transfer element to an analysis vessel,

wherein the transfer element is a liquid impermeable planar support element, and wherein the droplet adheres to a surface of the planar support element, and wherein the planar support element has a size which is greater than the diameter of the droplet.

31. A method of determining the volume of a droplet of a liquid said method comprising:

a) contacting a transfer element with the liquid to cause a droplet of the liquid to adhere to the transfer element,

b) illuminating the droplet and at least a part of the transfer element to produce at least one picture of the droplet and of a part of the transfer element on an optical sensor,

c) determining the contours of the droplet from the at least one picture produced on the optical sensor, and calculating the volume of the droplet from the so determined contours,

wherein said transfer element comprises a liquid impermeable planar surface element of a size which is greater than the diameter of the droplet, and wherein the step of determining the contours of the droplet occurs based upon the droplet when it is adhered to the transfer element.