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

• US 6,709,869 B2
• Filed: 11/20/2001
• Issued: 03/23/2004
• Est. Priority Date: 12/18/1995
• Status: Expired due to Fees

• Current Assignee: Tecan Trading AG (Tecan Group AG)
• Original Assignee: Tecan Trading AG (Tecan Group AG)
• Inventors: Mian, Alec, Corey, George D., Kieffer-Higgins, Stephen G.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): SINES, BRIAN J
• Application Number:
  US09/989,582
• Publication Number:
  US 20020137218A1
• Time in Patent Office: 854 Days
• Field of Search: 422/64, 422/50, 422/63, 422/67, 422/72, 436/45, 436/43, 436/63, 436/66, 436/70
• US Class Current: 436/45
• 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 25/31 in conduits or tubes through which the main component flows
• CPC Class Codes: B01F 33/00 Other mixers; Mixing plants; Combinations of mixers
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/71725 using centrifugal forces
• CPC Class Codes: B01F 35/71805 using valves, gates, orifices or openings
• 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: B01L 2200/027 for microfluidic devices
• 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 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0806 Standardised forms, e.g. compact disc [CD] format
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• 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 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/0633 : with moving parts
• CPC Class Codes: B01L 2400/0655 : pinch valves
• CPC Class Codes: B01L 2400/0661 : shape memory polymer valves
• 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 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• 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: B29C 59/14 : by plasma treatment plasma tubes per se H01J
• CPC Class Codes: F15C 1/005 : for measurement techniques, e.g. measuring from a distance; for detection devices, e.g. for presence detection; for sorting measured properties (testing); for gyrometers; for analysis; for chromatography fluid information or impulse transducers F15B5/00; postal sorting according to size B07C1/10; dial gauges, spherometers G01B3/22, G01B5/22; gyroscopic apparatus G01C19/00; viscosimeters G01N11/00; speed measurement, flowmeters G01P
• CPC Class Codes: F16K 2099/0074 : using photolithography, e.g. etching
• CPC Class Codes: F16K 2099/0076 : using electrical discharge machining [EDM], milling or drilling
• CPC Class Codes: F16K 2099/008 : Multi-layer fabrications
• CPC Class Codes: F16K 2099/0082 : Microvalves adapted for a particular use
• CPC Class Codes: F16K 2099/0084 : Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0013 : Rotary valves
• CPC Class Codes: F16K 99/0015 : Diaphragm or membrane valves
• CPC Class Codes: F16K 99/0017 : Capillary or surface tension valves, e.g. using electro-wetting or electro-capillarity effects
• CPC Class Codes: F16K 99/003 : Valves for single use only
• CPC Class Codes: F16K 99/0057 : the fluid being the circulating fluid itself, e.g. check valves
• CPC Class Codes: G01N 2030/326 : pumps
• CPC Class Codes: G01N 2035/00782 : reprogrammmable code
• CPC Class Codes: G01N 21/07 : Centrifugal type cuvettes G01N21/09 takes precedence
• CPC Class Codes: G01N 27/44704 : Details; Accessories
• CPC Class Codes: G01N 30/20 : using a sampling valve
• CPC Class Codes: G01N 30/6095 : Micromachined or nanomachined, e.g. micro- or nanosize
• 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: G01N 35/00732 : Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: G01N 35/00871 : Communications between instruments or with remote terminals
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/111666 : Utilizing a centrifuge or compartmented rotor

Abstract

This invention relates to methods and apparatus for performing microanalytic and microsynthetic analyses and procedures. The invention provides a microsystem platform and a micromanipulation device for manipulating the platform that utilizes the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels. The microsystem platforms of the invention are also optionally provided having system informatics and data acquisition, analysis and storage and retrieval informatics encoded on the surface of the disk opposite to the surface containing the fluidic components. Methods specific for the apparatus of the invention for performing any of a wide variety of microanalytical or microsynthetic processes are provided.

Claims

1. A method for measuring the amount of an analyte in a biological sample, the method comprising the steps of:

a) applying the biological sample to a sample inlet port of a microsystem platform of centripetally-motivated fluid micromanipulation apparatus comprising a microsystem platform, wherein the microsystem platform comprises;

i) a multiplicity of sample inlet ports, arranged concentrically around the center of the platform, wherein each of the sample inlet ports is operatively linked to

ii) a multiplicity of microchannels arrayed radially away from the center of the platform, said microchannels being operatively linked to

iii) a multiplicity of reagent reservoirs containing a reagent specific for the analyte to be measured, wherein release of the reagent from each of the reservoirs is controlled by a microvalve, wherein the microvalves are in electrical contact with a controller unit, and wherein the multiplicity of microchannels is also operatively linked to

iv) a multiplicity of analyte detection chambers arranged peripherally around the outer edge of the microplatform,

wherein movement of the biological sample from the sample inlet port and through the microchannel, and movement of the reagent from the reagent reservoir and through the microchannel, is motivated by centripetal force generated by rotational motion of the microsystem platform,

b) placing the microsystem platform in a micromanipulation apparatus,

c) providing rotational motion to the microsystem platform for a time and at a velocity sufficient to motivate the biological sample containing the analyte from the sample inlet port through the microchannel,

d) opening each of the microvalves controlling release of the reagent from the reagent reservoirs by generating a signal from the controlling unit, at a time and for a duration, whereby the reagent moves into the microchannel and is mixed with the biological sample,

e) observing the mixture of the biological sample and the reagent in the analyte detection chamber, whereby a detector within the micromanipulation apparatus detects a signal proportional to the amount of the analyte present in the biological sample, and

f) recording the measurement of the amount of the analyte in the biological sample.

2. The method of claim 1, wherein the biological sample is blood, urine, cerebrospinal fluid, plasma, saliva, semen, or amniotic fluid.

3. The method of claim 1, wherein the measurement of the amount of analyte in the sample is recorded in the device, on the microplatform, or both.

4. The method of claim 1, wherein the analyte detection chamber on the microsystem platform is optically transparent.

5. The method of claim 1, wherein the signal detected in the analyte detection chamber is detected at a frequency equal to the frequency of rotation of the platform or multiples thereof.

6. The method of claim 1, wherein the signal detected is a monochromatic light signal.

7. The method of claim 6, wherein the signal detected is a fluorescence signal, a chemiluminescence signal or a colorimetric signal.

8. A method for detecting gas or particles comprising an environmental sample, wherein the method comprises the steps of:

a) Contacting the environmental sample with a sample inlet port of a microsystem platform of a centripetally-motivated fluid micromanipulation apparatus comprising a microsystem platform, wherein the microsystem platform comprises;

i) a multiplicity of sample inlet ports, arranged concentrically around the center of the platform, wherein the sample ports comprise an air intake vent and a connecting funnel channel, wherein each of the sample inlet ports is operatively linked to

ii) a multiplicity of microchannels arrayed radially away from the center of the platform, said microchannels being operatively linked to

iii) a multiplicity of reagent reservoirs containing a reagent specific for the gas or particles to be detected, wherein release of the reagent from each of the reservoirs is controlled by a microvalve, wherein the microvalves are in electrical contact with a controller unit, and wherein the multiplicity of microchannels is also operatively linked to

iv) a multiplicity of gas or particle detectors arranged peripherally around the outer edge of the microplatform,

wherein movement of the environmental sample from the sample inlet port and through the microchannel, and movement of the reagent from the reagent from the reagent reservoir and through the microchannel is motivated by centripetal force generated by rotational motion of the micro system platform,

b) placing the mcirosystem platform in a micromanipulation device,

c) providing rotational motion to the microsystem platform for a time and at a velocity sufficient to motivate the gaseous or particulate environmental sample from the sample inlet port through the microchannel,

d) opening each of the microvalves controlling the release of the reagent from the reagent reservoirs by generating a signal from the controlling unit, at a time and duration wherby the reagent moves into the microchannel and is mixed with the environmental sample,

e) detecting the mixture of the environmental sample and the reagent or the gaseous or particulate component of the environmental sample directly in the gas or particle detection chamber, whereby each of the detectors detects a signal proportional to the amount of the gas or particulate present in the environmental sample, and

f) recording the measurement of the amount of the gas or particulate in the environmental sample.

9. The method of claim 8, wherein the environmental sample comprises air, water, soil, or disrupted biological matter.

10. The method of claim 8, wherein a gas is detected by a gas sensor chip.

11. The method of claim 8, wherein a particle is detected in an optically-transparent particle collection chamber.

12. The method of claim 8, wherein the particle is detected by coherent light scattering.

13. The method of claim 8, wherein a particle is detected in a particle collection chamber operatively connected by a microchannel to a reagent reservoir comprising a reagent for chemically testing the particles, wherein the particulate is mixed and reacted with the reagent in the microchannel after release of the reagent by activation of a microvalve and rotation of the platform.

14. A method for determining a hematocrit value from a blood sample, the method comprising the steps of

a) applying the blood sample to the proximal end of a microchannel of a microsystem platform of centripetally-motivated fluid micromanipulation apparatus comprising a micromanipulation device and a microsystem platform, wherein the microsystem platform comprises

i) a radial array of microchannels having a diameter of about 100 μ

m wherein the microchannels are treated with heparin to prevent coagulation, and wherein the microchannels are open at one end proximal to the center of the disk, the apparatus also comprising a coherent light source and a recording means operatively connected thereto comprising the micromanipulation device, and wherein movement of the blood sample through the microchannel is motivated by centripetal force generated by rotational motion of the microsystem platform,

b) placing the microsystems platform in a micromanipulation device,

c) providing rotational motion to the Microsystems platform for a time and at a velocity sufficient to motivate the red blood cells comprising the blood sample to move along the extent of the microchannel,

d) scanning the microchannel along its length with the coherent light source,

e) detecting a change in light scatter at a position along the microchannel that defines a boundary between the red blood cells and blood plasma,

f) recording the position of the boundary for each microchannel, and

g) comparing the position of this boundary for each microchannel with a standard curve relating hematocrit values to the position of the boundary, and recording the hematocrit determined thereby.