Nucleic acid detecting sensor, nucleic acid detecting chip, and nucleic acid detecting circuit

• US 20060147983A1
• Filed: 03/03/2006
• Published: 07/06/2006
• Est. Priority Date: 10/14/2004
• Status: Abandoned Application

• Current Assignee: Kabushiki Kaisha Toshiba (Toshiba Corporation)
• Original Assignee: Kabushiki Kaisha Toshiba (Toshiba Corporation)
• Inventors: O'uchi, Shin-ichi
• Application Number:
  US11/366,472
• Publication Number:
  US 20060147983A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors

Abstract

Nucleic acid detecting sensor includes field-effect transistor, detector which detects target nucleic acid molecules having sequences from sample based on degree of a variation in threshold voltage of field-effect transistor, and at least one nucleic acid probe molecule which is hybridized with corresponding one of target nucleic acid molecules, and is immobilized on gate of field-effect transistor, wherein gate width of field-effect transistor is of order of length obtained by expression given below (ε₀ε_rk_BT/e²n)^1/2 where ε0 is dielectric constant of vacuum, εr is relative dielectric constant of channel region, kB is Boltzmann constant, T is absolute temperature of the channel region, e is elementary charge, and n is equilibrium carrier density in the channel region in field-effect transistor where channel is formed.

Claims

1. A nucleic acid detecting sensor comprising:

a field-effect transistor;

a detector which detects target nucleic acid molecules having sequences from a sample based on a degree of a variation in threshold voltage of the field-effect transistor; and

at least one nucleic acid probe molecule which is hybridized with a corresponding one of the target nucleic acid molecules, and is immobilized on a gate of the field-effect transistor,

wherein a gate width of the field-effect transistor is of an order of a length obtained by an expression given below;

(ε

₀ε

_rk_BT/e²n)^1/2

where ε

₀ is a dielectric constant of a vacuum, ε

_r is a relative dielectric constant of a channel region, k_B is a Boltzmann constant, T is an absolute temperature of the channel region, e is elementary charge, and n is an equilibrium carrier density in the channel region in the field-effect transistor where a channel is formed.

2. The sensor according to claim 1, wherein a gate length of the field-effect transistor is of the same order as that of the gate width of the field-effect transistor and is greater than the gate width thereof.

4. A nucleic acid detecting chip including a plurality of nucleic acid detecting sensors according to claim 1,

wherein number of nucleic acid detecting sensors per unit area on the nucleic acid detecting chip is of an order that is equal to or greater than that of a value obtained by an expression given below:

1/Dt

where t is specified detection time and D is a diffusion constant of a nucleic acid molecule.

5. The nucleic acid detecting chip according to claim 4, wherein a density of target nucleic acid molecules included in the sample is estimated based on a ratio of the number of nucleic acid detecting sensors, which have detected the target nucleic acid molecules, to total number of nucleic acid detecting sensors.

6. A nucleic acid detecting chip including a plurality of nucleic acid detecting sensors according to claim 2,

wherein number of nucleic acid detecting sensors per unit area on the nucleic acid detecting chip is of an order that is equal to or greater than that of a value obtained by an expression given below:

1/Dt

where t is specified detection time and D is a diffusion constant of a nucleic acid molecule.

7. The nucleic acid detecting chip according to claim 6, wherein a density of target nucleic acid molecules included in the sample is estimated based on a ratio of the number of nucleic acid detecting sensors, which have detected the target nucleic acid molecules, to total number of nucleic acid detecting sensors.

10. A nucleic acid detecting circuit comprising:

a nucleic acid detecting sensor according to claim 1;

a zero-level detecting sensor having a gate on which a nucleic acid probe molecule is immobilized, the nucleic acid probe molecule differing from a nucleic acid probe molecule immobilized to the nucleic acid detecting sensor and having a sequence that fails to be complementary to nucleic acid molecules included in the sample;

two capacitive elements connected to a drain terminal of the nucleic acid detecting sensor and a drain terminal of the zero-level detecting sensor, respectively;

a sense amplifier which amplifies a difference in discharge rate between the field-effect transistor of the nucleic acid detecting sensor and that of the zero-level detecting sensor while those field-effect transistors discharge the capacitive elements charged with a present voltage; and

a determination unit configured to determine whether a target nucleic acid molecule is detected based on the difference in discharge efficiency.

11. A nucleic acid detecting circuit comprising:

a nucleic acid detecting sensor according to claim 2;

a zero-level detecting sensor having a gate on which a nucleic acid probe molecule is immobilized, the nucleic acid probe molecule differing from a nucleic acid probe molecule immobilized to the nucleic acid detecting sensor and having a sequence that fails to be complementary to nucleic acid molecules included in the sample;

two capacitive elements connected to a drain terminal of the nucleic acid detecting sensor and a drain terminal of the zero-level detecting sensor, respectively;

a sense amplifier which amplifies a difference in discharge rate between the field-effect transistor of the nucleic acid detecting sensor and that of the zero-level detecting sensor while those field-effect transistors discharge the capacitive elements charged with a present voltage; and

a determination unit configured to determine whether a target nucleic acid molecule is detected based on the difference in discharge efficiency.

13. A nucleic acid detecting circuit comprising:

a nucleic acid detecting sensor according to claim 1;

a zero-level detecting sensor having a gate on which a nucleic acid probe molecule is immobilized, the nucleic acid probe molecule differing from a nucleic acid probe molecule immobilized to the nucleic acid detecting sensor and having a sequence that fails to be complementary to nucleic acid molecules included in the sample;

a differential pair using the field-effect transistor of each of the nucleic acid detecting sensor and the zero-level detecting sensor as an input transistor; and

a determination unit configured to determine whether a target nucleic acid molecule is detected based on an intensity of an output voltage of the differential pair, which is generated by applying a common reference voltage to the differential pair.

14. A nucleic acid detecting circuit comprising:

a nucleic acid detecting sensor according to claim 2;

a zero-level detecting sensor having a gate on which a nucleic acid probe molecule is immobilized, the nucleic acid probe molecule differing from a nucleic acid probe molecule immobilized to the nucleic acid detecting sensor and having a sequence that fails to be complementary to nucleic acid molecules included in the sample;

a differential pair using the field-effect transistor of each of the nucleic acid detecting sensor and the zero-level detecting sensor as an input transistor; and

a determination unit configured to determine whether a target nucleic acid molecule is detected based on an intensity of an output voltage of the differential pair, which is generated by applying a common reference voltage to the differential pair.

3. A nucleic acid detecting sensor comprising:

a field-effect transistor;

a detector which detects target nucleic acid molecules having sequences from a sample based on a degree of a variation in threshold voltage of the field-effect transistor; and

at least one nucleic acid probe molecule which is hybridized with a corresponding one of the target nucleic acid molecules, and is immobilized on a gate of the field-effect transistor,

wherein a gate length of the field-effect transistor is of an order of a length obtained by an expression given below;

(ε

₀ε

_rk_BT/e²n)^1/2

where ε

₀ is a dielectric constant of a vacuum, ε

_r is a relative dielectric constant of a channel region, k_B is a Boltzmann constant, T is an absolute temperature of the channel region, e is elementary charge, and n is an equilibrium carrier density in the channel region in the field-effect transistor where a channel is formed.

8. A nucleic acid detecting chip including a plurality of nucleic acid detecting sensors according to claim 3,

wherein number of nucleic acid detecting sensors per unit area on the nucleic acid detecting chip is of an order that is equal to or greater than that of a value obtained by an expression given below:

1/Dt

where t is specified detection time and D is a diffusion constant of a nucleic acid molecule.

9. The nucleic acid detecting chip according to claim 8, wherein a density of target nucleic acid molecules included in the sample is estimated based on a ratio of the number of nucleic acid detecting sensors, which have detected the target nucleic acid molecules, to total number of nucleic acid detecting sensors.

12. A nucleic acid detecting circuit comprising:

a nucleic acid detecting sensor according to claim 3;

a zero-level detecting sensor having a gate on which a nucleic acid probe molecule is immobilized, the nucleic acid probe molecule differing from a nucleic acid probe molecule immobilized to the nucleic acid detecting sensor and having a sequence that fails to be complementary to nucleic acid molecules included in the sample;

two capacitive elements connected to a drain terminal of the nucleic acid detecting sensor and a drain terminal of the zero-level detecting sensor, respectively;

a sense amplifier which amplifies a difference in discharge rate between the field-effect transistor of the nucleic acid detecting sensor and that of the zero-level detecting sensor while those field-effect transistors discharge the capacitive elements charged with a present voltage; and

a determination unit configured to determine whether a target nucleic acid molecule is detected based on the difference in discharge efficiency.

15. A nucleic acid detecting circuit comprising:

a nucleic acid detecting sensor according to claim 3;

a zero-level detecting sensor having a gate on which a nucleic acid probe molecule is immobilized, the nucleic acid probe molecule differing from a nucleic acid probe molecule immobilized to the nucleic acid detecting sensor and having a sequence that fails to be complementary to nucleic acid molecules included in the sample;

a differential pair using the field-effect transistor of each of the nucleic acid detecting sensor and the zero-level detecting sensor as an input transistor; and

a determination unit configured to determine whether a target nucleic acid molecule is detected based on an intensity of an output voltage of the differential pair, which is generated by applying a common reference voltage to the differential pair.