Microchip for analysis, analysis system having the same, and analysis method

• US 20050255000A1
• Filed: 05/03/2005
• Published: 11/17/2005
• Est. Priority Date: 05/06/2004
• Status: Active Grant

• Current Assignee: Seiko Instruments Incorporated (Seiko Group)
• Original Assignee: Seiko Instruments Incorporated (Seiko Group)
• Inventors: Shinogi, Masataka, Yamamoto, Minao
• Granted Patent: US 7,842,240 B2
• Time in Patent Office: Days
• US Class Current: 422/68.100
• 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 2200/141 Preventing contamination, tampering
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 pinch valves
• 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 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites

Abstract

It is a problem to provide a microchip for analysis which is miniaturized, is disposable for ease to use, and does not have a risk of contamination in flow channels. On a substrate 2, a first flow channel having a buffer solution supply channel 6 and a reaction bath section 3, a second flow channel having a sample solution supply channel 5 and a waste solution channel 7, and a connecting channel 9 connecting both the flow channels upstream of the reaction bath section 3 are provided. The waste solution channel 7 and the reaction bath section 3 are connected to a waste solution tank 8 and a pump 11. After a ligand is modified in the reaction bath section 3, a sample solution is allowed to flow in the sample solution supply channel 5 and the waste solution channel 7, and a buffer solution is allowed to flow in the buffer solution supply channel 6, the connecting channel 9 and the waste solution channel 7, subsequently to flow in the buffer solution supply channel 6 and the reaction bath section 3. Then, a temperature adjusting section 13 and the pump 11 are set such that a desired temperature of a fluid and a flow rate are obtained. Subsequently, the sample solution is supplied to the sample solution supply channel 5, the connecting channel 9, and the reaction bath section 3, a binding reaction is brought between the ligand and an analyte in the sample solution, and the state of binding is detected.

Claims

1. A microchip for analysis comprising:

a substrate;

a reaction bath section;

a sample solution supply channel for supplying sample solution for analysis;

a buffer solution supply channel for supplying buffer solution;

a waste solution channel for discharging the solutions to an outside;

a first flow channel to which the buffer solution supply channel and the reaction bath section are connected;

a second flow channel to which the sample solution supply channel and the waste solution channel are connected; and

a connecting channel which is connected to an upstream side of the reaction bath section of the first flow channel from the second flow channel.

2. A microchip for analysis according to claim 1,

wherein the connecting channel is a flow channel which allows the buffer solution to flow from the buffer solution supply channel to the waste solution channel and which allows the sample solution to flow from the sample solution supply channel to the reaction bath section.

3. A microchip for analysis according to claim 1,

wherein the sample solution supply channel is provided with a sample solution introducing port through which the sample solution is dropped and supplied, and the buffer solution supply channel is provided with a buffer solution introducing port through which the buffer solution is dropped and supplied or the buffer solution supply channel is connected to a buffer solution tank which stores the buffer solution.

4. A microchip for analysis according to claim 1,

wherein the second flow channel is provided with valves which are respectively disposed upstream and downstream of the connecting channel and the first flow channel is provided with valves which are respectively disposed upstream and downstream of a portion to which the connecting channel is connected.

5. A microchip for analysis according to claim 1,

wherein the waste solution channel is connected to a waste solution tank which is provided outside the substrate.

6. A microchip for analysis according to claim 5,

wherein the reaction bath section is connected to the waste solution tank.

7. A microchip for analysis according to claim 5,

wherein the waste solution tank is connected to a pump which sucks up a fluid from at least one of the waste solution channel and the reaction bath section.

8. A microchip for analysis according to claim 1,

wherein a temperature adjusting section which adjusts a temperature of the fluid is provided in the reaction bath section of the first flow channel or upstream of the reaction bath section.

9. A microchip for analysis according to claim 8,

wherein the temperature adjusting section is provided downstream of the valve which is disposed upstream of the reaction bath section of the first flow channel.

10. A microchip for analysis according to claim 1, further comprising:

a third flow channel to which another buffer solution supply channel supplying the buffer solution and the reaction bath section are connected;

a fourth flow channel to which a treatment solution supply channel supplying treatment solution and the waste solution channel are connected; and

a connecting channel for treatment solution which is connected to an upstream side of the reaction bath section of the third flow channel from the fourth flow channel.

11. A microchip for analysis according to claim 10,

wherein another buffer solution supply channel of the third flow channel is a flow-channel which is branched from the buffer solution supply channel of the first flow channel to reach the reaction bath section.

12. A microchip for analysis according to claim 10,

wherein the connecting channel for treatment solution is a flow channel which allows the buffer solution to flow from the buffer solution supply channel to the waste solution channel and which allows the treatment solution to flow from the treatment solution supply channel to the reaction bath section.

13. A microchip for analysis according to claim 10,

wherein the fourth flow channel is provided with valves which are respectively disposed upstream and downstream of the connecting channel for treatment solution, and the third flow channel is provided with valves which are respectively disposed upstream and downstream of a portion to which the connecting channel for treatment solution is connected.

14. A microchip for analysis according to claim 10,

wherein at least one other flow channel for treatment solution is connected to the fourth flow channel.

15. An analysis system comprising:

a microchip for analysis according to claim 1;

a mounting section on which the microchip for analysis is mounted;

a solution transfer section which causes at least the sample solution and the buffer solution to flow in the microchip for analysis mounted on the mounting section;

a sensor section which detects a reaction in the reaction bath section; and

an analysis section which analyzes the detection result from the sensor section.

16. A analysis system according to claim 15,

wherein the sensor section is built in the reaction bath section of the microchip for analysis.

17. A analysis system according to claim 15,

wherein the analysis section is included in a computer which controls operations of the valve provided on the microchip for analysis and the pump connected to the microchip for analysis.

18. An analysis method using a microchip for analysis which includes a reaction bath section, a sample solution supply channel for supplying sample solution for analysis, a buffer solution supply channel for supplying buffer solution, a waste solution channel for discharging the solutions to an outside, a first flow channel to which the buffer solution supply channel and the reaction bath section are connected, a second flow channel to which the sample solution supply channel and the waste solution channel are connected, and a connecting channel which is connected to an upstream side of the reaction bath section of the first flow channel from the second flow channel, the analysis method comprising:

a step of extracting air from the sample solution supply channel and the waste solution channel by allowing the sample solution to flow from the sample solution supply channel via the waste solution channel to the outside;

a step of extracting air from the buffer solution supply channel, the connecting channel, and the waste solution channel by allowing the buffer solution to flow from the buffer solution supply channel via the connecting channel and the waste solution channel to the outside;

a step of extracting air from the buffer solution supply channel and the reaction bath section by allowing the buffer solution to flow from the buffer solution supply channel via the reaction bath section to the outside; and

a step of, after the respective steps of extracting air are completed, supplying the sample solution to the reaction bath section from the sample solution supply channel via the connecting channel and causing and detecting a chemical reaction of the sample solution in the reaction bath section.

19. An analysis method according to claim 18,

wherein the step of supplying the sample reaction to the reaction bath section to cause and detect the chemical reaction is started while a flow in the reaction bath section is maintained by allowing the buffer solution to continuously flow to the reaction bath section.

20. An analysis method according to claim 19, further comprising:

when the step of extracting air from the buffer solution supply channel, the connecting channel, and the waste solution channel and/or the step of extracting air from the sample solution supply channel and the waste solution channel are performed after the step of extracting air from the buffer solution supply channel and the reaction bath section,

a step of allowing the buffer solution to flow in the first flow channel after the respective steps of extracting air are completed and before the step of supplying the sample solution to the reaction bath section to cause and detect the chemical reaction.

21. An analysis method according to claim 18,

wherein the step of supplying the sample solution to the reaction bath section to cause and detect the chemical reaction is performed while adjusting the temperature of the sample solution by means of a temperature adjusting section provided in the reaction bath section of the first flow channel or upstream of the reaction bath section.

22. An analysis method according to claim 21,

wherein the temperature adjusting section is provided downstream of the valve which is disposed upstream of the reaction bath section of the first flow channel.

23. An analysis method according to claim 21,

wherein, before the step of supplying the sample solution to the reaction bath section to cause and detect the chemical reaction, operation conditions for the temperature adjusting section are preliminarily set when the buffer solution is flowing in the reaction bath section.

24. An analysis method according to claim 18,

wherein the sample solution is supplied by dropping the sample solution onto a sample solution introducing port provided on the sample solution supply channel and the buffer solution is supplied by dropping the buffer solution onto a buffer solution introducing port provided on the buffer solution supply channel.

25. An analysis method according to claim 18,

wherein both a fluid discharged from the waste solution channel and a fluid discharged from the reaction bath section are caused to flow in a waste solution tank which is provided outside the substrate and which is connected to the waste solution channel and the reaction bath section.

26. An analysis method according to claim 25,

wherein flows of the buffer solution and the sample solution are controlled by open and close operations of each of valves respectively provided upstream and downstream of the connecting channel of the second flow channel, open and close operations of each of valves respectively provided upstream and downstream of a portion of the first flow channel connected to the connecting channel, and an operation of a fluid sucking-up pump connected to the waste solution tank.

27. An analysis method according to claim 18, further comprising:

whenever the step of supplying the sample solution to the reaction bath section to cause and detect the chemical reaction is completed,

a step of removing the microchip for analysis to replace with a new microchip for analysis.

28. An analysis method according to claim 18,

wherein a ligand is preliminarily modified in the reaction bath section and the sample solution containing an analyte is supplied to the reaction bath section to cause and detect the chemical reaction.

29. An analysis method according to claim 18, further comprising:

using the microchip for analysis which further includes a third flow channel to which another buffer solution supply channel for supplying the buffer solution and the reaction bath section are connected, a fourth flow channel to which a treatment solution supply channel for supplying a treatment solution and the waste solution channel are connected, and a connecting channel for treatment solution which is connected to an upstream side of the reaction bath section of the third flow channel from the fourth flow channel,

a step of allowing the buffer solution to flow from the buffer solution supply channel via the connecting channel for treatment solution to the waste solution channel; and

a step of allowing the treatment solution to flow from the treatment solution supply channel via the connecting channel for treatment solution to the reaction bath section.

30. An analysis method according to claim 29,

wherein another buffer solution supply channel of the third flow channel is a flow channel which is branched from the buffer solution supply channel of the first flow channel to reach the reaction bath section.

31. An analysis method according to claim 30, further comprising:

using the microchip for analysis in which at least one other flow channel for treatment solution is connected to the fourth flow channel,

a step of allowing another treatment solution to flow from the other flow channel for treatment solution via the connecting channel for treatment solution to the reaction bath section.