Nucleic acid detecting cassette, nucleic and detecting apparatus utilizing nucleic acid detecting cassette, and nucleic acid detecting system utilizing nucleic acid detecting cassette

• US 20050153430A1
• Filed: 11/22/2004
• Published: 07/14/2005
• Est. Priority Date: 11/28/2003
• Status: Active Grant

• Current Assignee: Kabushiki Kaisha Toshiba (Toshiba Corporation)
• Original Assignee: Kabushiki Kaisha Toshiba (Toshiba Corporation), Toshiba Tec Corporation (Toshiba Corporation)
• Inventors: Ohtaka, Yoshimitsu
• Granted Patent: US 7,135,330 B2
• Time in Patent Office: Days
• US Class Current: 435/287.200
• 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 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• 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 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001

Abstract

A nucleic acid detecting cassette comprises a fluid holding channel capable of varying the inner volume and holding a reagent, an inlet-outlet port connected to the fluid holding channel and capable of selecting an opened state under which the fluid injection out of the outer portion of the cassette can be achieved and a closed state under which the fluid injection can be interrupted, joining channels connected to the fluid holding channel and capable of selecting an opened state under which the fluid transfer to the other fluid holding channel can be achieved and a closed state under which the fluid transfer can be interrupted, inlet-outlet pads capable of maintaining the inlet-outlet port under a closed state, and joining pads capable of maintaining the joining channels under a closed state.

Claims

1. A nucleic acid detecting cassette for detecting nucleic acid contained in a sample, comprising:

a stationary member;

a flexible member provided on the stationary member, the stationary member and flexible member forming a fluid holding channel, a joining channel and an inlet-outlet port therebetween, the fluid holding channel being configured to be able to vary its inner volume, and hold a reagent, the inlet-outlet port being connected to the fluid holding channel and being selectively set to one of an open-state under which the fluid holding channel is communicated with the outside of the cassette through the port and a closed-state under which the fluid holding channel is discommunicated with the outside of the cassette, the joining channel being connected to the fluid holding channel and being selectively set to one of an open-state under which the communication with the fluid holding channel is made and a closed-state under which the communication with the fluid holding channel is interrupted;

a first opening-closing part configured to maintain the inlet-outlet port under the closed-state; and

a second opening-closing part configured to maintain the joining channel under the closed-state.

2. The nucleic acid detecting cassette according to claim 1, wherein the first opening-closing part is formed of a flexible member, and the inlet-outlet port is sealed by the flexible member.

3. The nucleic acid detecting cassette according to claim 1, wherein the second opening-closing part is formed of a flexible member, and the joining channel is sealed by the flexible member.

4. The nucleic acid detecting cassette according to claim 1, wherein:

the nucleic acid detecting cassette comprises a detecting channel formed between the stationary member and the flexible member, configured to immobilize a nucleic acid probe of a single stranded nucleic acid having a base sequence complementary to that of nucleic acid that is to be detected; and

the detecting channel is connected to the fluid holding channel via the joining channel.

5. The nucleic acid detecting cassette according to claim 1, wherein the fluid holding channel includes a channel starting edge portion and a channel terminating edge portion, and the inlet-outlet port is formed in each of the channel starting edge portion and the channel terminating edge portion of the fluid holding channel.

6. The nucleic acid detecting cassette according to claim 1, wherein the fluid holding channel includes a channel starting edge portion and a channel terminating edge portion, and the joining channel is provided to at least one of the channel starting edge portion and the channel terminating edge portion of the fluid holding channel.

7. The nucleic acid detecting cassette according to claim 1, wherein the first opening-closing part includes a part configured to open and close the inlet-outlet port by utilizing the mobility of the flexible member.

8. The nucleic acid detecting cassette according to claim 1, wherein the second opening-closing part includes a part configured to open and close the joining channel by utilizing the mobility of the flexible member.

9. The nucleic acid detecting cassette according to claim 4, wherein the detecting channel further includes a retreating channel, in which a prescribed loading material is loaded, configured to retreat the loaded material in a detecting stage of nucleic acid in the detecting channel, the inner volume of the retreating channel being maintained under a decreased state before the start-up of the detecting stage of nucleic acid, being capable of enlargement at the time of start-up of the detecting stage, and the difference in the inner volume of the channel between enlarged time and the decreased time being not smaller than the volume of the loaded material within the detecting channel.

10. The nucleic acid detecting cassette according to claim 4, wherein a prescribed loading material is loaded in the detecting channel, and the fluid holding channel acts as a retreating channel configured to retreat the loaded material in the stage of detecting nucleic acid in the detecting channel.

11. The nucleic acid detecting cassette according to claim 4, wherein the detecting channel shares at least one of the stationary member and the flexible member collectively constituting the fluid holding channel and the joining channel.

12. The nucleic acid detecting cassette according to claim 9, wherein:

the detecting channel includes a channel starting edge portion and a channel terminating edge portion;

first and second joining channels are provided to the channel starting edge portion and the channel terminating edge portion, respectively;

the first joining channel is joined to the fluid holding channel; and

the second joining channel is joined to the retreating channel.

13. The nucleic acid detecting cassette according to claim 1, further comprising a pushing member configured to push the flexible member constituting the fluid holding channel from outside the nucleic acid detecting cassette, such that the inner volume of the fluid holding channel is decreased or the inner pressure of the fluid holding channel is increased by the pushing member.

14. A nucleic acid detecting device for detecting nucleic acid contained in a sample, comprising:

a nucleic acid detecting cassette including;

a stationary member,

a flexible member provided on the stationary member, the stationary member and flexible member forming a fluid holding channel, a joining channel and an inlet-outlet port therebetween, the fluid holding channel being configured to be able to vary its inner volume, the inlet-outlet port being connected to the fluid holding channel and being selectively set to one of an open-state under which the fluid holding channel is communicated with the outside of the cassette through the port and a closed-state-under which the fluid holding channel is discommunicated with the outside of the cassette, the joining channel being connected to the fluid holding channel and being selectively set to one of an open-state under which the communication with the fluid holding channel is made and a closed-state under which the communication with the fluid holding channel is interrupted,

a detecting channel being connected to the fluid holding channel via the joining channel,

a first opening-closing part configured to maintain the inlet-outlet port under the closed-state, and

a second opening-closing part configured to maintain the joining channel under the closed-state;

a reagent loaded in the fluid holding channel of the nucleic acid detecting cassette; and

a nucleic acid probe of a single stranded nucleic acid immobilized within the detecting channel of the nucleic acid detecting cassette and having a base sequence complementary to that of the nucleic acid to be detected.

15. The nucleic acid detecting device according to claim 14, wherein a prescribed loading material is being loaded in the detecting channel included in the nucleic acid detecting cassette.

16. The nucleic acid detecting device according to claim 14, wherein the pressure increase inside the fluid holding channel causes the flexible member to be expanded toward the outside of the nucleic acid detecting cassette so as to increase the inner volume of the fluid holding channel.

17. A nucleic acid detecting system for detecting nucleic acid contained in a sample, using

a nucleic acid detecting device including:

a stationary member,

a flexible member provided on the stationary member, the stationary member and flexible member forming a fluid holding channel, a joining channel and an inlet-outlet port therebetween, the fluid holding channel being configured to be able to vary its inner volume, the inlet-outlet port being connected to the fluid holding channel and being selectively set to one of an open-state under which the fluid holding channel is communicated with the outside of the cassette through the port and a closed-state under which the fluid holding channel is discommunicated with the outside of the cassette, the joining channel being connected to the fluid holding channel and being selectively set to one of an open-state under which the communication with the fluid holding channel is made and a closed-state under which the communication with the fluid holding channel is interrupted,

a detecting channel being connected to the fluid holding channel via the joining channel capable of immobilizing a nucleic acid probe of a single stranded nucleic acid having a base sequence complementary to that of nucleic acid that is to be detected,

a first opening-closing part configured to maintain the inlet-outlet port under the closed-state, and

a second opening-closing part configured to maintain the joining channel under the closed-state;

the nucleic acid detecting system comprising;

a device holding part configured to hold the device;

a first driving mechanism configured to deform a first part of the flexible member corresponding to a first region of the fluid holding channel within the device held by the device holding part so as to deform the fluid holding channel;

a second driving mechanism configured to deform a second part of the flexible member corresponding to a second region of the fluid holding channel within the device held by the device holding part so as to deform the fluid holding channel;

a third driving mechanism configured to drive the second opening-closing part; and

a temperature control part configured to control the temperature of at least one of the fluid holding channel and the detecting channel.

18. The nucleic acid detecting system according to claim 17, wherein at least two of the first driving mechanism, the second driving mechanism, and the third driving mechanism are formed of a common driving mechanism.

19. The nucleic acid detecting system according to claim 17, wherein:

the fluid holding channel includes a first fluid holding channel and a second fluid holding channel;

the joining channel serves to join the first fluid holding channel and the second fluid holding channel to each other; and

the temperature control part includes a first temperature control part configured to control the temperature of the first fluid holding channel and a second temperature control part configured to control the temperature of the second fluid holding channel.

20. The nucleic acid detecting system according to claim 17, wherein:

the joining channel serves to join the fluid holding channel and the detecting channel to each other; and

the temperature control part includes a first temperature control part configured to control the temperature of the fluid holding channel and a second temperature control part configured to control the temperature of the detecting channel.

21. The nucleic acid detecting system according to claim 17, wherein:

the device includes a pushing member configured to push the flexible member constituting the fluid holding channel from outside the device; and

the nucleic acid detecting system further includes a part configured to allow the pushing member to be selectively located in a position facing the surface of the flexible member constituting the fluid holding channel and a position retreating from the surface of the flexible member, the temperature control part being selectively positioned close to, brought into contact with and pushed against the surface of the flexible member when the pushing member is in the retreating position.

22. The nucleic acid detecting system according to claim 17, wherein:

the device includes at least two fluid holding channels and detecting channels arranged in series, and

the temperature control part includes a first temperature control part configured to control the temperature of one of one fluid holding channel and one detecting channel and a second temperature control part configured to control the temperature of one of the other fluid holding channel and the other detecting channel.