Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system for performing biological fluid assays

• US 6,632,399 B1
• Filed: 05/19/1999
• Issued: 10/14/2003
• Est. Priority Date: 05/22/1998
• Status: Expired due to Term

• Current Assignee: Tecan Trading AG (Tecan Group AG)
• Original Assignee: Tecan Trading AG (Tecan Group AG)
• Inventors: Morneau, Keith, Jensen, Mona D., Lin, Hsin Chiang, Pierce, Andrea, Kellogg, Gregory, Kieffer-Higgins, Stephen G., Kob, Mikayla, Ommert, Shari
• Primary Examiner(s): LUDLOW, JAN M
• Application Number:
  US09/315,114
• Time in Patent Office: 1,609 Days
• Field of Search: 422/72, 422/101, 436/45, 436/177
• US Class Current: 422/72
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 2101/44 Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/7172 using capillary forces
• CPC Class Codes: B01F 35/71725 using centrifugal forces
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• 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 2300/0806 Standardised forms, e.g. compact disc [CD] format
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0406 capillary forces
• 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 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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: F16K 31/002 actuated by temperature variation thermo-electric F16K31/025
• CPC Class Codes: G01N 21/07 : Centrifugal type cuvettes G01N21/09 takes precedence
• CPC Class Codes: G01N 21/78 : producing a change of colour
• CPC Class Codes: G01N 35/00069 : whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
• CPC Class Codes: H01C 17/06586 : composed of organic material
• CPC Class Codes: H01R 39/64 : Devices for uninterrupted current collection
• CPC Class Codes: Y10T 436/111666 : Utilizing a centrifuge or compartmented rotor
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

This invention provides methods and apparatus for performing microanalytic and microsynthetic analyses and procedures. Specifically, the invention provides a microsystem platform for use with a micromanipulation device to manipulate the platform by rotation, thereby utilizing the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels embedded in the microplatform. The microsystem platforms of the invention are also provided having microfluidics components, resistive heating elements, temperature sensing elements, mixing structures, capillary and sacrificial valves, and methods for using these microsystems platforms for performing biological, enzymatic, immunological and chemical assays.

Claims

1. A microsystem platform for performing an assay to detect an analyte in a fluid sample, comprising:

a) a rotatable platform, comprising a substrate having a first flat, planar surface and a second flat, planar surface opposite thereto, each surface comprising a center about which the platform is rotated, wherein the first surface comprises in combination

b) an entry port comprising a depression in the first surface having a volumetric capacity of about 1 to about 150 μ

L, that is fluidly connected with

c) a capillary microchannel having a cross-sectional diameter of less than 800 microns, that is further fluidly connected with

d) an assay chamber fluidly connected with the entry port, the assay chamber further comprising

i) a porous matrix comprising reagents for performing an analyte detection assay, wherein the porous matrix has an average pore size that prevents cells from entering the matrix; and

wherein a fluid sample applied to the entry port is delivered to the assay chamber through the capillary microchannel by rotation of the platform, and wherein delivery of the fluid sample to the assay chamber initiates the analyte detection assay.

2. The microsystem platform of claim 1 wherein the entry port is fluidly connected with

e) an entry passageway having a cross-sectional diameter of about 0.1 mm to about 5 mm that is fluidly connected with

f) a fluid entry chamber comprising a fluid metering volume and an overflow passageway, wherein the overflow passageway is further connected to an overflow capillary, wherein the overflow capillary is further fluidly connected to

g) an overflow chamber comprising a first shallow outer portion having a depth from about 0.05 mm to about 0.5 mm and an inner portion having a depth of from about 0.1 mm to 5 mm;

wherein the overflow capillary is fluidly connected with the overflow chamber at a position on the platform that is at least 20% farther from the center of rotation that the fluid metering volume, and wherein the overflow and fluid chambers also comprise air displacement channels whereby air displaced by fluid movement is vented from the platform.

3. The microsystem platform of claim 1 further comprising

e) a metering capillary and an overflow capillary, each being fluidly connected with the entry port, wherein each capillary defines a cross-sectional area of about 0.02 mm to about 800 microns in diameter, and wherein each capillary extends radially from the center of the platform and defines a first end proximally arrayed towards the center of the platform and a second end distally arrayed from the center of the platform, wherein the proximal end of each capillary defines a curved opening;

wherein the metering capillary defines a volume of the fluid and wherein the metering capillary is fluidly connected with the assay chamber and wherein the overflow capillary is fluidly connected with

f) an overflow chamber having a depth equal to or greater than the overflow capillary depth and positioned radially more distant from the center of the platform than the assay chamber and the entry port,

wherein a capillary junction is formed at the junction of the metering capillary and the assay chamber and at the junction of the overflow capillary and the overflow chamber, whereby fluid in the entry port flows by capillary action to the junction of the metering capillary and the assay chamber, and excess fluid flows by capillary action to the junction of the overflow capillary and the overflow chamber; and

wherein rotation of the platform at a first rotation speed motivates fluid displacement in the overflow capillary into the overflow chamber but not fluid displacement in the metering capillary, whereby rotation of the platform at a first rotational speed drains the fluid from the entry port into the overflow chamber; and

wherein rotation of the platform at a second rotational speed that is greater than the first rotational speed motivates fluid displacement of the volume of the fluid in the metering capillary into the assay chamber; and

wherein each of the assay chamber and overflow chamber also comprise air displacement channels whereby air displaced by fluid movement is vented from the platform.

4. The microsystem platform of claim 3, wherein the porous matrix comprises a hydrophilic matrix.

5. The microsystem platform of claim 4, wherein said analyte detection assay is a glucose detection assay.

6. The microsystem platform of claim 3, further comprising

g) a sacrificial valve between the metering capillary and the assay chamber, wherein release of the sacrificial valve permits fluid flow from the metering capillary to the assay chamber at a non-zero rotational speed.

7. The microsystem platform of claim 6 wherein the sacrificial valve is a solid, semi-solid or viscous liquid hydrocarbon, or a plastic.

8. The microsystem platform of claim 7 further comprising a heating element in the platform in thermal contact with the sacrificial valve, wherein heating the heating element releases the sacrificial valve.

9. The microsystem platform of claim 3, wherein the assay chamber has a top and bottom surface and the chamber further comprises

e) a depression in the bottom surface of the assay chamber having a volumetric capacity about equal to the volume contained in the metering capillary.

10. The microsystem platform of claim 9, wherein the top surface of the assay chamber is translucent.

11. The microsystem platform of claim 1 further comprising

e) a read chamber fluidly connected to the assay chamber by a first microchannel, and

f) a wash buffer reservoir containing a wash buffer and fluidly connected to the assay chamber by a second microchannel

wherein rotation of the platform at a rotational speed greater than the rotational speed of the platform that delivers the fluid sample to the assay chamber motivates wash buffer through the second microchannel and into the assay chamber, whereby the wash buffer displaces the fluid sample from the assay chamber and into the read chamber through the first microchannel.

12. The microsystem platform of claim 11, further comprising

g) a sacrificial valve in the second microchannel, wherein release of the sacrificial valve permits wash buffer flow from the wash buffer reservoir to the assay chamber when the platform is rotated at a non-zero rotational speed.

13. The microsystem platform of claim 12 wherein the sacrificial valve is a solid, semi-solid or viscous liquid hydrocarbon, or a plastic.

14. The microsystem platform of claim 13 further comprising a heating element in the platform in thermal contact with the sacrificial valve, wherein heating the heating element releases the sacrificial valve.

15. The microsystem platform of claim 11, wherein the read chamber comprises a top surface that is translucent.

16. The microsystem platform of claim 15, wherein the assay chamber has a top and bottom surface and the chamber further comprises

e) a depression in the bottom surface of the assay chamber having a volumetric capacity about equal to the volume contained in the metering capillary and in fluidic contact with the second matrix element.