Microfluidic devices and systems for separating components of a mixture

• US 20030027225A1
• Filed: 07/12/2002
• Published: 02/06/2003
• Est. Priority Date: 07/13/2001
• Status: Abandoned Application

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Holdings Incorporated
• Inventors: Chow, Andrea W., Wada, H. Garrett, Bousse, Luc J.
• Application Number:
  US10/194,978
• Publication Number:
  US 20030027225A1
• Time in Patent Office: Days
• US Class Current: 435/7.21
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: G01N 1/34 Purifying; Cleaning processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2001/4038 electric methods, e.g. electromigration, electrophoresis, ionisation
• CPC Class Codes: G01N 2015/149 Sorting the particles
• CPC Class Codes: G01N 27/44717 Arrangements for investigating the separated zones, e.g. localising zones
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027

Abstract

The present invention provides systems, devices and methods for performing fast and efficient separation and collection of components of a sample mixtures. The present invention provides integrated systems for performing separation using a multi port control system to sort and collect components of sample mixtures.

Claims

1. A method for sorting components of a sample mixture having a desired activity, comprising:

providing a microfluidic device having a microscale channel network, wherein said channel network is in fluid communication with a plurality of reservoirs;

flowing a sample mixture into a first microchannel within said microscale channel network;

flowing a first reactant to mix with said sample mixture within said first microchannel;

detecting an interaction between said sample mixture and said first reactant;

isolating components of said sample mixture that exhibit said desired activity based on information received at the detector; and

delivering said components into a receptacle located external to the microfluidic device.

2. The method of claim 1, wherein the sample mixture comprises a cellular suspension.

3. The method of claim 1, wherein the first reactant comprises an agonist.

4. The method of claim 2, wherein the cellular suspension comprises cells labeled with a fluorescent dye.

5. The method of claim 1, wherein flowing of said sample mixture and said first reactant comprises applying a pressure differential along the first microchannel to flow the sample mixture and the first reactant along the first microchannel.

6. The method of claim 5 wherein the pressure differential is applied by applying an elevated pressure at a first end of the first microchannel.

7. The method of claim 1, wherein flowing of said sample mixture and said first reactant comprises applying an electric field along said first microchannel, the electrical field being sufficient to cause electrokinetic flowing of said sample mixture and said first reactant.

8. The method of claim 2, wherein said cellular suspension comprises blood cells.

9. The method of claim 8, wherein said blood cells comprise one or more of B cells, T cells, monocytes and neutrophils.

10. The method of claim 1 wherein said sample mixture comprises a suspension of beads have cells adhered thereto.

11. The method of claim 2, wherein detecting an interaction of the sample mixture and said first reactant further comprises measuring a function of cells in the cellular suspension.

12. The method of claim 2, wherein detecting an interaction of the sample mixture and said first reactant further comprises measuring an effect of the first reactant on a function of the cells in the cellular suspension.

13. The method of claim 2, wherein the first reactant comprises a test compound.

14. The method of claim 2, wherein the cellular suspension comprises one or more of mammalian cells, insect cells, bacterial cells, fungal cells, yeast cells and plant cells.

15. The method of claim 2, wherein the cellular suspension comprises mammalian cells.

16. The method of claim 2, wherein the isolating step comprises hydrodynamically focusing cells in the cellular suspension to flow single file along a first side of said first microchannel.

17. The method of claim 16, wherein the hydrodynamically focusing of the cells comprises flowing a fluid from a second microchannel into said first microchannel.

18. The method of claim 1, wherein the detecting step comprises optically detecting an interaction between said sample mixture and said first reactant.

19. The method of claim 18, wherein said optically detecting comprises fluorescence detection.

20. The method of claim 1, wherein said receptacle is one or more of a well on a microtiter plate, a petri dish, a reservoir on the microfluidic device and a container.

21. The method of claim 1 further comprising providing a processor which is operably coupled to a detector for performing the detection step and to a fluid direction system for controlling movement of components having the desired activity into the receptacle, based on information received from said detector.

22. The method of claim 21 wherein said processor includes a computer which includes appropriate programming for receiving a signal from the detector that is indicative of the desired activity, and for directing the fluid direction system to direct components having the desired activity from the first microchannel into the receptacle.

23. The method of claim 2 wherein the desired activity is selected from one based on differential permeability or binding of one or more cells in the cellular suspension to a fluorescent dye or dye conjugate including calcein AM, BCECF AM, ethidium bromide, propidium iodide, a cationic dye, a cationic membrane permeable dye, a neutral dye, a membrane permeable neutral dye, an anionic dye, or an anionic membrane permeable dye

24. The method of claim 2 wherein the desired activity is the level of calcium flux across the membrane of one or more cells in the cellular suspension.

26. The method of claim 24, wherein the desired property comprises a physical property.

25. A method for sorting components of a sample mixture having a desired property, comprising:

providing a microfluidic device having a microscale channel network, wherein said channel network is in fluid communication with a plurality of reservoirs;

flowing a sample mixture into a first microchannel within said microscale channel network;

flowing a first reactant to mix with said sample mixture within said first microchannel;

detecting an interaction between said sample mixture and said first reactant;

isolating components of said sample mixture that exhibit said desired property based on information received at the detector; and

delivering said components into a receptacle located external to the microfluidic device.

27. The method of claim 25, wherein the physical property is size.