Micro-reactor device for minute sample analysis

• US 5,480,614 A
• Filed: 03/16/1994
• Issued: 01/02/1996
• Est. Priority Date: 03/16/1993
• Status: Expired due to Fees

• Current Assignee: Hitachi, Ltd.
• Original Assignee: Hitachi, Ltd.
• Inventors: Kamahori, Masao
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Pyon, Harold Y.
• Application Number:
  US08/213,526
• Time in Patent Office: 657 Days
• Field of Search: 422/50, 422/58, 422/70, 422/68.1, 422/73, 422/81, 422/82.05, 422/102, 422/104, 422/108, 422/116, 422/145, 422/211, 422/213, 436/52, 436/178, 436/150, 436/806, 436/533, 436/541, 204/299 R
• US Class Current: 422/70
• 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 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00889 Mixing micromixers B01F33/30
• 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 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1894 Cooling means; Cryo cooling
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• 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: G01N 2030/027 Liquid chromatography
• CPC Class Codes: G01N 2030/162 electromigration
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 30/06 Preparation
• CPC Class Codes: G01N 30/24 Automatic injection systems
• CPC Class Codes: G01N 35/08 using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: Y10S 436/806 : Electrical property or magnetic property
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream

Abstract

A minute sample analysis system includes a micro-reactor device, a quantitative measuring device, an analyzing device and a controller, whereby, when a very small amount of sample is handled, its dilution and loss can be suppressed to minimum level, and analyzing operations ranging from reaction with a reactive reagent to separation/detection of the sample can be consistently carried out efficiently. The micro-reactor device controls the solution, reactive reagent and sample flowing in the form of electroosmotic flow generated by high-voltage application under control of passage change-over switches. The quantitative measuring device measures the quantity of reactive sample received from the micro-reactor device and introduces the measured reactive sample into the analyzing device. The analyzing device optically detects components separated from the sample through electrophoresis. The above operations are generally controlled under by the controller.

Claims

1. A micro-reactor device for causing a reaction between a sample and a reagent, said device comprising:

a sample reservoir for holding a sample;

a reagent reservoir for holding a reagent;

a first waster reservoir for holding a first waste solution;

a second waste reservoir for holding a second waste solution;

means defining a first passage connecting said reagent reservoir and said first waster reservoir;

a first passage switch in said first passage, for controlling flow therethrough;

a second passage switch in said first passage, intermediate said first passage switch and said first waste reservoir, for controlling flow therethrough;

means defining a second passage connecting said sample reservoir and said first passage at a first junction intermediate said first and second passage switches;

a third passage switch in said second passage, for controlling flow therethrough;

means defining a third passage connecting said second waster reservoir and said first passage at a second junction intermediate said first and second passage switches;

a fourth passage switch in said third passage, for controlling flow therethrough;

generating means for applying a voltage to said passage to cause electroosomotic flow of fluids in said passages; and

a controller for controlling said passage switches and said generating means, to cause elecroosomotic flow of reagent in said first passage followed by electroosomotic flow of a predetermined volume of sample in said first sample passage between the first junction ad the second junction and then electroosomotic flow of reagent in said first passage.

2. A micro-reactor device as claimed in claim 1, wherein:

a first planar insulator substrate and a second planar insulator substrate are provided, the first planar insulator substrate having a bonding surface and the second planar insulator substrate having a bonding surface bonded to the bonding surface of said first planar insulator substrate;

one of said planar insulator substrates has first, second, third, and fourth openings therethrough to provide, respectively, the sample reservoir, the reagent reservoir, the first waste reservoir, and the second waste reservoir; and

one of said bonding surfaces has first, second and third grooves formed therein to define, respectively, the first passage, the second passage, and the third passage.

3. A micro-reactor device as claimed in claim 1, further comprising an optical measuring device, including a measuring chamber within said first passage at a point intermediate said second passage switch and said first waster reservoir, a light source for radiating light into said measuring chamber for reflection, and a light detector for detecting light reflected from said measuring chamber to detect fluids therein.

4. A micro-reactor device as claimed in claim 1, wherein said generating means comprises:

first, second, third, and fourth electrodes positioned, respectively, in said sample reservoir, in said reagent reservoir, in said first waste reservoir, and in said second waste reservoir;

a first power supply for supplying voltage between said second and third electrodes; and

a second power supply for supplying voltage between said first and fourth electrodes.

5. A micro-reactor device as claimed in claim 1, wherein each of said grooves has a diameter of 100 μ

m or less.

6. A micro-reactor device as claimed in claim 3, wherein said measuring chamber comprises a light transmitting portion in one of said substrates for transmitting light to said first passage and a light reflector in said first passage for reflecting the light transmitted by said light transmitting portion.

7. A micro-reactor device for causing a reaction between a sample and a reagent, said device comprising:

a first planar insulator substrate having a bonding surface;

a second planar insulator substrate having a bonding surface bonded to the bonding surface of said first planar insulator substrate,

one of said planar insulator substrates having first, second, third, and fourth openings therethrough to provide, respectively, a sample reservoir, a reagent reservoir, a first waste reservoir, and a second waste reservoir, and one of said bonding surfaces having first, second and third grooves formed therein to provide, respectively, a first passage connecting said reagent reservoir and said first waste reservoir, a second passage connecting said sample reservoir and said first passage, and a third passage connecting said second waster reservoir and said first passage;

first, second, third, and fourth electrodes positioned, respectively, in said sample reservoir, in said reagent reservoir, in said first waste reservoir, and in said second waster reservoir;

a first passage switch in said first passage, intermediate said reagent reservoir and said second and third passages, for controlling flow therethrough;

a second passage switch in said first passage, intermediate said second and third passages and said first waste reservoir, for controlling flow therethrough;

a third passage switch in said second passage, for controlling flow therethrough;

a fourth passage switch in said third passage, for controlling flow therethrough;

an optical measuring device, including a measuring chamber within said first passage at a point intermediate said second passage switch and said first waste reservoir, a light source for radiating light into said measuring chamber for reflection, and a light detector for detecting light reflected from said measuring chamber to detect fluids therein;

a first power supply for supplying voltage between said second and third electrodes;

a second power supply for supplying voltage between said first and fourth electrodes; and

a controller for controlling said passage switches and said power supplies, to control flow between said reservoirs through said passages.

8. A micro-reactor device as claimed in claim 7, wherein each of said grooves has a diameter of 100 μ

m or less.

9. A micro-reactor device as claimed in claim 7, wherein each of said passage switches controls flow by freezing and unfreezing an adjacent part of the passage.

10. A micro-reactor device as claimed in claim 7, wherein each of said passage switches comprises a plug for plugging the passage.

11. A micro-reactor device as claimed in claim 7, wherein said measuring chamber comprises a light transmitting portion in one of said planar insulator substrates for transmitting light to said first passage and a light reflector in said first passage for reflecting the light transmitted by said light transmitting portion.