Method for carrying out an electrochemical measurement on a liquid measuring sample in a measuring chamber that can be accessed by lines, and corresponding arrangement

• US 20090136922A1
• Filed: 10/17/2005
• Published: 05/28/2009
• Est. Priority Date: 10/15/2004
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Siemens AG
• Inventors: Barlag, Heike, Paulicka, Peter, Gumbrecht, Walter, Stanzel, Manfred, Kuhn, Daniela, Birkle, Siegfried
• Granted Patent: US 7,851,227 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Especially in order to carry out the so-called enzyme-coupled DNA hybridisation test in a closed cartridge including a microfluid system, using stored dry reagents, the reagents must be dissolved in the microfluid system and transported into the measuring chamber directly before the measurement. During the dissolution of the reagents in water, air cushions that cannot reach the measuring chamber must absolutely be prevented from forming upstream of the reagent liquid. According to an embodiment of the invention, the liquid measuring sample and the liquid reagents are transported in such a way that the air cushion is directed into the waste line and the measuring sample and the reagents are then introduced into the measuring chamber without any air bubbles. In this way, measuring errors can be avoided.

Claims

1. A method for bringing at least one reagent, in liquid form and supplied for an electrochemical measurement on a measuring sample in a measuring chamber accessible via lines, for interaction with the measuring sample, the method comprising:

pumping the measuring sample through an access point into the measuring chamber and bringing an excess of the measuring sample into a first waste line on an opposite side of the measuring chamber;

delivering the at least one reagent from a line, initially without flowing through the measuring chambers, into a second waste line on a same side of the measuring chamber; and

bringing the at least one reagent, free from air bubbles, through the measuring chamber to the first waste line for interaction with the measuring sample.

2. The method as claimed in claim 1, wherein the measuring sample and the at least one reagent are supplied to the measuring chamber through different access points.

3. The method as claimed in claim 1, wherein the measuring sample and the air cushion in front of at least one reagent are delivered into different waste channels.

4. The method as claimed in claim 1, wherein there is no air in the measuring chamber after the measuring sample and the reagents have been delivered through the measuring chamber.

5. The method as claimed in claim 1, wherein the at least one reagent includes two reagents.

6. The method as claimed in claim 1, wherein the liquid of the at least one reagent is produced “

in situ”

by dissolving at least one solid pre-dosed and pre-portioned dry reagents by supplying a solvent.

7. The method as claimed in claim 6, wherein water is used as the solvent.

8. The method as claimed in claim 1, wherein application for enzyme-linked DNA hybridization detection with prior PCR, to which end a cartridge with a PCR chamber and at least one of label-enzyme- and enzyme-substrate reagent lines is used.

9. The method as claimed in claim 7, wherein the reagent lines are filled with water during the PCR.

10. The method as claimed in claim 8, wherein air is discharged from the at least one of label-enzyme- and enzyme-substrate reagent lines after the hybridization, so that the detection chamber is subsequently flushed initially with the first reagent without an air cushion and subsequently with the second reagent without an air cushion, and wherein the electrochemical measurement is subsequently carried out.

15. The arrangement as claimed in claim 1, wherein the lines for reagents and the measuring sample access point are arranged on opposite sides of the measuring chamber.

16. The method as claimed in claim 2, wherein the measuring sample and the air cushion in front of at least one reagent are delivered into different waste channels.

17. The method as claimed in claim 2, wherein there is no air in the measuring chamber after the measuring sample and the reagents have been delivered through the measuring chamber.

18. The method as claimed in claim 2, wherein the at least one reagent includes two reagents.

19. The method as claimed in claim 5, wherein the liquids of the two reagents are produced “

in situ”

by dissolving solid pre-dosed and pre-portioned dry reagents by supplying a solvent.

20. The method as claimed in claim 19, wherein water is used as the solvent.

11. An arrangement for bringing at least one reagent, in liquid form and supplied for an electrochemical measurement on a measuring sample in a measuring chamber accessible via lines, for interaction with the measuring sample, the arrangement comprising:

a measuring chamber including at least two access points, a first access point being connected to a first line for waste and a second access point being connected to a further line for waste, the measuring sample being pumpable through at least one access point into the measuring chamber, wherein an excess of the measuring sample is disposable into the first waste line, the at least one reagent being deliverable into the second waste line, and the at least one reagent being usable for interaction with the measuring sample.

12. The arrangement as claimed in claim 11, wherein the one access point forms the interface both for the supply line of the measuring sample and for at least one of the waste lines.

13. The arrangement as claimed in claim 11, wherein the other access point forms the interface both for the at least one reagent and for at least one waste line.

14. The arrangement as claimed in claim 11, wherein lines for two reagents are provided.

21. The arrangement as claimed in claim 12, wherein the other access point forms the interface both for the at least one reagent and for at least one waste line.

22. The arrangement as claimed in claim 12, wherein lines for two reagents are provided.

23. The arrangement as claimed in claim 13, wherein lines for two reagents are provided.