Method for the automated analysis of liquid samples using centrifugal force in a microfluidic structure

• US 8,580,567 B2
• Filed: 10/13/2010
• Issued: 11/12/2013
• Est. Priority Date: 10/14/2009
• Status: Active Grant

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Sarofim, Emad, Oosterbroek, Edwin, Cherubini, Claudio, Milicevic, Nenad
• Primary Examiner(s): Soderquist, Arlen
• Assistant Examiner(s): Adams, Michelle
• Application Number:
  US12/903,492
• Publication Number:
  US 20110250695A1
• Time in Patent Office: 1,126 Days
• Field of Search: None
• US Class Current: 436/45
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: G01N 2021/0325 Cells for testing reactions, e.g. containing reagents
• CPC Class Codes: G01N 2035/00099 Characterised by type of test elements
• CPC Class Codes: G01N 2035/00495 Centrifuges
• CPC Class Codes: G01N 21/07 Centrifugal type cuvettes G01N21/09 takes precedence
• CPC Class Codes: G01N 35/00029 provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: Y10T 436/111666 Utilizing a centrifuge or compartmented rotor

Abstract

A method for the automated analysis of liquid samples using at least one microfluidic structure is disclosed as well as microfluidic structures, a device having at least one of the microfluidic structures, a kit and a system including such microfluidic device. In one embodiment, the method may comprise: transferring a sample into a first fluid reservoir which is in fluid communication with a second fluid reservoir by a flow channel; spinning the microfluidic structure so as to transport the sample into one or more dead-end recesses or chambers; transferring a control fluid into the structure which generates a barrier to flow and diffusion of the sample contained in the one or more dead-end recesses or chambers; and analyzing the sample contained in the one or more dead-end recesses or chambers.

Claims

1. A method for the automated analysis of at least one liquid sample involving the use of at least one microfluidic structure, the method comprising:

providing at least one microfluidic structure adapted for spinning around a spin axis to generate a centrifugal force wherein said at least one microfluidic structure comprises an inner position and an outer position relative to said spin axis in a direction of said centrifugal force, said at least one microfluidic structure including;

a first fluid reservoir and a second fluid reservoir located at said inner position relative to said spin axis and only in fluid communication with each other by a U-shaped flow channel located at an outer position relative to said spin axis, said flow channel comprising a first channel portion and a second channel portion linearly extending along said direction of said centrifugal force, said first channel portion and said second channel portion connected at said outer position by a third channel portion extending in a direction orthogonal to said centrifugal force, said first fluid reservoir and said second fluid reservoir open into said first channel portion and said second channel portion respectively by a first reservoir opening and a second reservoir opening such that said first reservoir opening and said second reservoir opening have a non-zero distance with respect to each other in said direction of said centrifugal force; and

one or more dead-end recesses, said one or more dead-end recesses being in fluid communication with said flow channel by one or more respective recess openings provided only in said first channel portion;

transferring said at least one liquid sample into said first fluid reservoir;

spinning said at least one microfluidic structure around said spin axis so as to transport said at least one liquid sample into said one or more dead-end recesses by said centrifugal force;

transferring a control fluid into said first fluid reservoir or said second fluid reservoir;

spinning said at least one microfluidic structure around said spin axis to transport said control fluid into said flow channel by said centrifugal force so that said control fluid is at least present at said one or more respective recess openings of said one or more dead-end recesses, said control fluid generating a barrier to flow and diffusion of said at least one liquid sample contained in said one or more dead-end recesses; and

analyzing said at least one liquid sample contained in said one or more dead-end recesses.

2. The method according to claim 1, wherein said at least one liquid sample and one or more reagents for reacting with said at least one liquid sample are transferred into said one or more dead-end recesses.

3. The method according to claim 2, further comprising solidifying said control fluid in at least a contact area of said at least one liquid sample and said control fluid.

4. The method according to claim 1, further comprising solidifying said control fluid in at least a contact area of said at least one liquid sample and said control fluid.

5. The method according to claim 4, wherein solidification of said control fluid is initiated by a triggering agent.

6. The method according to claim 4, wherein solidification of said control fluid is initiated by water contained in said at least one liquid sample.

7. The method according to claim 1, further comprising cycling said at least one liquid sample contained in said one or more dead-end recesses through a series of temperature excursions.

8. The method according to claim 1, wherein said one or more dead-end recesses are one or more reaction chambers and said one or more respective recess openings are one or more chamber openings.