Miniaturized integrated nucleic acid processing and analysis device and method

• US 20050019902A1
• Filed: 08/14/2004
• Published: 01/27/2005
• Est. Priority Date: 09/28/1995
• Status: Abandoned Application

• Current Assignee: Eric T. Lagally, Peter C. Simpson, Richard A. Mathies
• Original Assignee: Eric T. Lagally, Peter C. Simpson, Richard A. Mathies
• Inventors: Simpson, Peter C., Lagally, Eric T., Mathies, Richard A.
• Application Number:
  US10/918,575
• Publication Number:
  US 20050019902A1
• Time in Patent Office: Days
• US Class Current: 435/287.200
• 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 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• 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 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• 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 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/049 : vacuum
• CPC Class Codes: B01L 2400/0605 : check valves
• CPC Class Codes: B01L 2400/0611 : duck bill valves
• CPC Class Codes: B01L 2400/0633 : with moving parts
• CPC Class Codes: B01L 2400/0683 : mechanically breaking a wall or membrane within a channel or chamber
• 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 3/502723 : characterised by venting arrangements
• 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 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• 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 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046

Abstract

A miniature device has a body including one, two or more reaction chambers. The reaction chambers are constructed for one or more of the following: sample acquisition, preparation or analysis. Preferably, a sample preparation reaction includes nucleic acid extraction, amplification, nucleic acid fragmentation, labeling, extension or a transcription.

Claims

1. A miniature device comprising:

a body having a reaction chamber disposed therein;

a resistive heater electrically connected to a power source for applying power to said heater to facilitate a reaction in said reaction chamber;

a temperature sensor disposed on a surface of said body for determining a temperature within said reaction chamber; and

an appropriately programmed computer for monitoring said temperature and operating said power source to selectively apply said power to said heater.

2. The miniature device of claim 1, further comprising a second reaction chamber fluidly connected to said reaction chamber.

3. The miniature device of claim 2, wherein said second reaction chamber comprises a microcapillary electrophoresis device.

4. The miniature device of claim 2, wherein said second reaction chamber has an oligonucleotide array disposed therein, said oligonucleotide array including a substrate having a plurality of positionally distinct oligonucleotide probes coupled to a surface of said substrate.

5. The miniature device of claim 1, wherein said body comprises at least first and second planar members, said first planar member having a first surface and a well disposed in said first surface, said second planar member having a second surface, said second surface being mated to said first surface whereby said well forms said cavity.

6. The miniature device of claim 5, wherein said temperature sensor is deposited on said second surface wherein when said second surface is mated with said first surface, said temperature sensor on said second surface is positioned within said cavity whereby a temperature at said temperature sensor is substantially the same as a temperature within said cavity.

7. The device of claim 1, wherein said reaction chamber has a volume of from about 0.001 μ

1 to about 10 μ

l.

8. The device of claim 1, wherein said reaction chamber has a volume of from about 0.01 μ

l to about 1 μ

l.

9. The device of claim 1, wherein said reaction chamber has a volume of from about 0.05 μ

l to about 0.5 μ

l.

10. The device of claim 1, wherein said temperature sensor comprises a thermocouple having a sensing junction positioned adjacent said cavity, and a reference junction positioned outside of said cavity, said thermocouple being electrically connected to a detector for measuring a voltage across said thermocouple.

11. The device of claim 10, wherein said detector for measuring a voltage across said thermocouple measures a DC voltage.

12. The device of claim 10, wherein said thermocouple comprises a first gold film adjoined to a chromium film as said sensing junction and said chromium film adjoined to a second gold film as said reference junction.

13. The device of claim 1, wherein said resistive heater comprises a chromium film and said electrical connection comprises two gold leads overlaying said chromium film and being electrically connected to said power source.

14. The miniature device of claim 1, wherein said first reaction chamber comprises a PCR chamber.

15. The miniature device of claim 1, wherein said vent includes a hydrophobic vent.

16. The miniature device of claim 1 further including a valve constructed to seal input to said reaction chamber.

17. The miniature device of claim 16, wherein said valve includes a diaphragm valve.

18. The miniature device of claim 1, wherein said reaction chamber is in communication with a sealable opening constructed and arranged for introduction of said liquid into said reaction chamber.

19. The miniature device of claim 18, wherein said sealable opening includes a septum.

20. A miniature device comprising:

a body including at least two reaction chambers arranged in parallel, each said reaction chamber being constructed to separately receive a liquid;

each said reaction chamber being in fluid communication with a vent;

at least two resistive heaters electrically connected to a power source for applying power;

each said heater being constructed to deliver heat to one said reaction chamber;

at least two temperature sensors for determining separately a temperature within said reaction chambers; and

an appropriately programmed computer for monitoring said temperature and operating said power source to selectively apply said power to each said heater to facilitate separate reactions in said reaction chambers,

wherein each said vent enables removal of gas from the corresponding reaction chamber thereby preventing a temperature variation in said liquid during said reaction.

21. The miniature device of claim 20, wherein at least one of said first reaction chambers comprises a PCR chamber.

22. The miniature device of claim 20, wherein at least one of said vents includes a hydrophobic vent.

23. The miniature device of claim 20 further including at least one valve constructed to seal input to at least one said reaction chamber.

24. The miniature device of claim 23, wherein said at least one valve includes a diaphragm valve.

25. The miniature device of claim 20, wherein at least one of said reaction chambers is in communication a sealable opening constructed and arranged for introduction of said liquid into said reaction chamber.

26. The miniature device of claim 25, wherein said sealable opening includes a septum.

27. A miniature device comprising:

a body having a reaction chamber disposed therein and constructed to receive a liquid;

a vent in fluid communication with said reaction chamber;

a resistive heater electrically connected to a power source for applying power to said heater;

a temperature sensor disposed on a surface of said body for determining a temperature within said reaction chamber; and

an appropriately programmed computer for monitoring said temperature and operating said power source to selectively apply said power to said heater to facilitate a reaction in said reaction chamber,

wherein said vent enables removal of gas from said reaction chamber thereby preventing a temperature variation in said liquid during said reaction.