Microfluidic system including a virtual wall fluid interface port for interfacing fluids with the microfluidic system

• US 20040091398A1
• Filed: 06/25/2003
• Published: 05/13/2004
• Est. Priority Date: 06/20/2001
• Status: Active Grant

• Current Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Original Assignee: Teragenics, Inc.
• Inventors: Gilbert, John R., Chiem, Nghia H.
• Granted Patent: US 7,211,442 B2
• Time in Patent Office: Days
• US Class Current: 422/504
• CPC Class Codes: B01D 57/02 by electrophoresis treatment of water, waste water, sewage or sludge by electrophoresis C02F1/469; electrophoretic production of compounds or non-metals C25B7/00; investigating or analysing materials by using electrophoresis G01N27/26
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00371 comprising electrodes
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00837 comprising coatings other than catalytically active coatings
• CPC Class Codes: B01J 2219/00869 Microreactors placed in parallel, on the same or on different supports
• CPC Class Codes: B01J 2219/00889 Mixing micromixers B01F33/30
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/00905 Separation
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• CPC Class Codes: B01L 2400/0439 : ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 3/0244 : using pins
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502792 : for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: C12Q 1/00 : Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• CPC Class Codes: G01N 2035/1037 : Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 27/447 : using electrophoresis
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44782 : of a plurality of samples
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/118339 : with formation of a segmented stream
• CPC Class Codes: Y10T 436/13 : Tracers or tags
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A fluid interface port in a microfluidic system and a method of forming the fluid interface port is provided. The fluid interface port comprises an opening formed in the side wall of a microchannel sized and dimensioned to form a virtual wall when the microchannel is filled with a first liquid. The fluid interface port is utilized to perform a labeling operation on a sample.

Claims

1. A method of labeling a sample, comprising:

conveying the sample through a channel having a first virtual wall fluid interface port;

separating the sample in the channel into a plurality of bands; and

injecting a labeling solution through the first virtual wall fluid interface port, wherein the labeling solution interacts with one of said bands to form a labeled band.

2. The method of claim 1, further comprising the step of detecting the labeled band.

3. The method of claim 1, further comprising the step of ejecting at least a portion of the labeled band from the channel.

4. The method of claim 3, wherein the step of ejecting a portion of the labeled band comprises ejecting at least a portion of the labeled band through a second virtual wall interface port in the form of one or more droplets.

5. The method of claim 1, wherein the labeling solution comprises a labeled species and a binding molecule for binding to a selected band and the labeled species.

6. The method of claim 5, wherein the step of injecting the labeling solution comprises injecting the labeled species through the first virtual wall fluid interface port and injecting the binding molecule through a second virtual wall fluid interface port.

7. The method of claim 1, wherein the virtual wall fluid interface port has a diameter between about 25 μ

m and about 100 μ

m, such that when a fluid is disposed in the interior of the channel, the fluid forms a virtual wall at the virtual wall fluid interface port.

8. The method of claim 1, further comprising the step of separating the plurality of bands in to a plurality of sub-bands.

9. The method of claim 1, further comprising the step of transferring a labeled band to one of a MALDI-MS system and a multi-well plate for further analysis.

10. A method of labeling a sample, comprising:

conveying the sample through a channel having a virtual wall fluid interface port; and

injecting a labeling solution through the virtual wall fluid interface port, wherein the labeling solution interacts with the sample to label the sample.

11. The method of claim 11, further comprising the step of separating the sample into a plurality of bands.

12. A system for performing a labeling operation, comprising:

a column for conveying a sample mixture through the system, wherein the column comprises an interior bounded by a side wall;

a separation region for separating the sample mixture into a plurality of bands;

a first fluid interface port downstream of the separation region for injecting labeling molecules into the interior of the column.

13. The system of claim 12, further comprising a detector downstream of the first fluid interface port for identifying bands of the sample mixture in the column.

14. The system of claim 12, further comprising a second fluid interface port downstream of the first fluid interface port for injecting a binding molecule into the column.

15. The system of claim 12, further comprising an ejector for ejecting a band of the sample mixture from the column.

16. The system of claim 12, wherein the ejector comprises a pressure pulse generator, said pressure pulse generator comprising a conical-shaped pressure chamber disposed opposite a second fluid interface port and in communication with the interior of the column and a piezo-actuated membrane connected to the pressure chamber.

17. The system of claim 12, wherein the ejector comprises a pin assembly comprising a first pin and a second pin spaced from the first pin to define a capillary for receiving a liquid volume.

18. The system of claim 12, further comprising a second fluid interface port formed in the side wall of the column upstream of the separation region for injecting the sample mixture into the column.

19. The system of claim 12, wherein the fluid interface port has a diameter between about 25 μ

m and about 100 μ

m, such that when a fluid is disposed in the interior of the microchannel, the fluid forms a virtual wall at the fluid interface port.

20. The system of claim 12, further comprising:

a second fluid interface port upstream of the separation region for injecting the sample mixture into the column;

a third fluid interface port downstream of the second fluid interface port for injecting a binding molecule into the column, whereby the binding molecule and the labeled molecules interact with a selected band to form a labeled band;

a detector downstream of the third fluid interface port for identifying the labeled band; and

an ejector for ejecting the labeled band from the column.