Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis

• US 5,858,195 A
• Filed: 02/03/1997
• Issued: 01/12/1999
• Est. Priority Date: 08/01/1994
• Status: Expired due to Term

• Current Assignee: Lockheed Martin Energy Research Corporation (Martin Marietta Corporation)
• Original Assignee: Lockheed Martin Energy Research Corporation (Martin Marietta Corporation)
• Inventors: Ramsey, J. Michael
• Primary Examiner(s): Warden, Robert J.
• Assistant Examiner(s): STARSIAK, JOHN S
• Application Number:
  US08/776,645
• Time in Patent Office: 708 Days
• Field of Search: 204/450, 204/451, 204/452, 204/453, 204/455, 204/600, 204/601, 204/602, 204/603, 204/604, 204/605
• US Class Current: 204/601
• CPC Class Codes: B01D 15/3842 Micellar chromatography
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• 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 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00826 Quartz
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00889 Mixing micromixers B01F33/30
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/00912 by electrophoresis
• CPC Class Codes: B01J 2219/00916 by chromatography
• CPC Class Codes: B01J 2219/00952 Sensing operations
• CPC Class Codes: B01J 2219/0097 Optical sensors
• CPC Class Codes: B01J 2219/00995 Mathematical modeling
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0883 : Serpentine channels
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 : electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• 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 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 3/502776 : specially adapted for focusing or laminating flows
• CPC Class Codes: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B29C 65/4895 : Solvent bonding, i.e. the surfaces of the parts to be joined being treated with solvents, swelling or softening agents, without adhesives
• CPC Class Codes: B29C 66/026 : Chemical pre-treatments B29C66/028 takes precedence
• CPC Class Codes: B29C 66/034 : Thermal after-treatments
• CPC Class Codes: B29C 66/54 : Joining several hollow-preforms, e.g. half-shells, to form hollow articles, e.g. for making balls, containers; Joining several hollow-preforms, e.g. half-cylinders, to form tubular articles
• CPC Class Codes: G01N 2030/027 : Liquid chromatography
• CPC Class Codes: G01N 2030/162 : electromigration
• CPC Class Codes: G01N 2030/285 : electrically driven carrier
• CPC Class Codes: G01N 2030/383 : by using auxiliary fluid
• CPC Class Codes: G01N 2030/8435 : for chemical reaction
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 30/02 : Column chromatography
• CPC Class Codes: G01N 30/16 : Injection G01N30/24 takes precedence
• CPC Class Codes: G01N 30/6095 : Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: Y10S 366/01 : Micromixers: continuous laminar flow with laminar boundary mixing in the linear direction parallel to the fluid propagation with or without conduit geometry influences from the pathway

Abstract

A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.

Claims

1. A microchip laboratory system for analyzing or synthesizing chemical material, comprising:

a body having disposed therein, a plurality of integrated channels connecting a plurality of at least five reservoirs, at least one reservoir having at least a first material disposed therein, and each of at least five of the reservoirs simultaneously having separate controlled electrical potentials associated therewith, said electrical potentials presenting a voltage gradient between one reservoir and at least one other reservoir, to transport said first material from said at least one other reservoir through at least one of the plurality of integrated channels toward at least one of the other reservoirs to expose said first material to one or more selected chemical or physical environments.

2. The system of claim 1, wherein said first material is a fluid.

3. The system of claim 1, wherein said plurality of integrated channels comprises:

at least three of said plurality of integrated channels in fluid communication at a first intersection, each of said at least three channels connecting said first intersection with a separate one of at least three of the reservoirs; and

wherein said electrical potentials simultaneously associated with said at least three reservoirs simultaneously transport materials from at least two of the reservoirs to the first intersection, to mix the materials from the at least two reservoirs at the first intersection.

4. The system of claim 3, wherein an electrical potential at the first intersection is less than the electrical potential associated with each of the at least two reservoirs.

5. The system of claim 1, wherein said plurality of integrated channels comprises:

at least first, second, third, and fourth channels in fluid communication at a first intersection, said first, second, third, and fourth channels connecting first, second, third and fourth reservoirs to said intersection respectively; and

wherein said electrical potential controls the volume of a first material transported from the first reservoir to the second reservoir through the first intersection by transporting a second material from the third reservoir through the first intersection.

6. The system of claim 5, wherein the electrical potential selectively transports the second material from the third reservoir through the first intersection toward the second or fourth reservoirs.

7. The system of claim 5, wherein the electrical potentials transport the second material through the first intersection preventing the first material from moving through the first intersection toward the second reservoir, after a selected volume of the first material has passed the first intersection toward the second reservoir.

8. The system of claim 5, wherein the electrical potentials transport the first and second materials into the first intersection and toward the second reservoir.

9. The system of claim 1, wherein the plurality of integrated channels comprises:

a first channel connecting a first and a second of said at least five reservoirs, a second channel connecting a third and a fourth of said at least five reservoirs the first channel and the second channel intersecting at a first intersection; and

a third channel connecting a fifth of the at least five reservoirs, with the second channel at a location between the first intersection and the fourth reservoir.

10. The system of claim 9, wherein said electrical potentials simultaneously transport material from the fifth reservoir and material from the first intersection toward the fourth reservoir, to mix the materials from the first intersection and the fifth reservoir.

11. The system of claim 9 wherein the third channel connects the fifth reservoir with a sixth reservoir, the third channel intersecting the second channel;

at a second intersection the second intersection being located at a point on the third channel between the fifth and sixth reservoirs.

12. The system of claim 11, wherein the electrical potentials simultaneously transport material from the fifth and sixth reservoirs into the second intersection.

13. The system of claim 12, wherein the electrical potentials transport material from the firth and sixth reservoirs through the second intersection toward the first intersection and toward the fourth reservoir, after a selected volume of material from the first intersection is transported through the second intersection toward the fourth reservoir.

14. A microchip flow system, comprising:

a body having first and second channels disposed therein the first channel connecting first and second reservoirs, the first reservoir having a first material disposed therein, and the second channel connecting third and fourth reservoirs, the first channel intersecting the second channel at a point on the first channel between the first and second reservoirs to form a first intersection, and in which at least three of the reservoirs simultaneously have controlled electrical potentials associated therewith said electrical potentials effecting transport of a volume of first material from the first reservoir to the second reservoir through the first intersection, said volume being selectively controlled by the movement of a material from the third reservoir through the first intersection toward another reservoir.

15. The system of claim 14 wherein the first material is a fluid.

16. The system of claim 14 wherein the electrical potentials transport a second material from the third reservoir through the first intersection toward the second reservoir.

17. The system of claim 15 wherein the electrical potentials transport the second material from the third reservoir through the first intersection toward the fourth reservoir preventing the first material from moving through the first intersection toward the second reservoir after a selected volume of the first material has passed through the first intersection toward the second reservoir.

18. The system of claim 15 electrical potentials simultaneously transport the first and second materials from the first intersection toward the second reservoir.

19. The system of claim 14 further comprising a third channel that connects a fifth reservoir with the first channel at a location between the first intersection and the second reservoir.

20. The system of claim 19, further comprising:

an additional electrical potential associated with the fifth reservoir, the additional electrical potential transporting material from the fifth reservoir with material transported from the first intersection toward the second reservoir.

21. The system of claim 19, further comprising a sixth reservoir having a controlled electrical potential associated therewith, the third channel connecting the fifth and sixth reservoirs and crossing the first channel at a second intersection between the firth and sixth reservoirs.

22. The system of claim 21, further wherein the electrical potentials simultaneously transport material from the fifth and sixth reservoirs into the second intersection.

23. The system of claim 21, wherein the electrical potentials simultaneously transport material from the fifth and sixth reservoirs through the second intersection and toward the second reservoir.

24. A microflow control system, comprising a body having integrated channels connecting at least four reservoirs, wherein first and second reservoirs of the four reservoirs contain first and second materials, respectively, a channel connecting the first reservoir and a third reservoir forming an intersection with a channel connecting the second and a fourth reservoir;

and

a voltage controller that;

applies an electrical potential difference between the first reservoir and the third reservoir, and selectively applies a potential difference between the second and fourth reservoirs or the second and third reservoirs to transport a selected, variable volume of the first material from the first reservoir through the intersection toward the third reservoir.

25. A method of controlling the flow of material through an interconnected channel system having at least first and second channels and at least four reservoirs, the first channel connecting first and third reservoirs and the second channel connecting second and fourth reservoirs, wherein the first reservoir contains a first material, the first channel intersecting the second channel at a first intersection between the first and third reservoirs, the method comprising:

applying an electrical potential difference between the first reservoir and the third reservoir in a manner that transports a selected, variable volume of the first material from the first reservoir through the intersection toward the third reservoir; and

after a selected time period, simultaneously applying a selected electrical potential to each of at least three of the four reservoirs in a manner that inhibits the movement of the first material through the intersection toward the third reservoir.