Chemical sensor system

• US 20070054266A1
• Filed: 05/28/2003
• Published: 03/08/2007
• Est. Priority Date: 05/28/2002
• Status: Abandoned Application

• Current Assignee: National Institute of Advanced Industrial Science and Technology (Government of Japan)
• Original Assignee: National Institute of Advanced Industrial Science and Technology (Government of Japan)
• Inventors: Miyake, Jun, Yoshikawa, Tomohiro, Miyake, Masato, Sato, Takaaki, Hamana, Hiroshi, Hirono, Junzo
• Application Number:
  US10/516,210
• Publication Number:
  US 20070054266A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: G01N 33/02 Food
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

A chemical sensor utilizing a chemical receptor (for example, one stimulating the sense of taste or smell) is provided. More specifically speaking, such a receptor is introduced into cells and the cells are immobilized on a support to form a chip. This chip is then employed as a component of a sensor. This sensor shows a reaction almost the same as the body'"'"'s perception of the taste or smell or sense, thereby enabling analysis. Thus, it is also usable as an artificial sensory organ. Moreover, this sensor is usable in diagnosis, which imparts a high industrial usefulness to it.

Claims

1. A chemical sensor comprising:

a) a nucleic acid comprising a sequence encoding a chemical receptor gene;

b) a support with a cell located thereon, wherein the cell has the nucleic acid introduced therein;

c) means for measuring a signal caused by the chemical receptor; and

d) means for providing information relating to a chemical by calculating the extent of activation of the chemical receptor from the intensity of the measured signal.

2. The sensor according to claim 1, wherein said nucleic acid further comprises a sequence encoding a marker gene.

3. The sensor according to claim 1, wherein said chemical receptor comprises a receptor selected from the group consisting of nuclear receptors, cytoplasmic receptors and cellular membrane receptors.

4. The sensor according to claim 1, wherein said chemical receptor is selected from the group consisting of G protein coupled receptors, kinase type receptors, ion-channel type receptors, nuclear receptors, hormone receptors, chemokine receptors, and cytokine receptors.

5. The sensor according to claim 1, wherein said chemical receptor comprises an olfactory receptor.

6. The sensor according to claim 1, wherein said chemical receptor gene is selected from the group consisting of retinoic acid receptors, EGF receptors, interleukin receptors, and CSF receptors.

7. The sensor according to claim 1, wherein said chemical receptor gene comprises a nucleic acid sequence or a variant or fragment thereof, selected from the group consisting of SEQ ID NO:

1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94 and 96.

8. The sensor according to claim 1, wherein said chemical receptor gene comprises at least about two species.

9. The sensor according to claim 1, wherein said chemical receptor gene comprises at least about ten species.

10. The sensor according to claim 1, wherein said chemical receptor gene comprises at least about twenty species.

11. The sensor according to claim 1, wherein said chemical receptor gene comprises at least about three hundred species.

12. The sensor according to claim 1, wherein said chemical receptor gene comprises substantially all species which are possessed by an animal selected from the group consisting of mice, humans, rats, dogs and cats.

13. The sensor according to claim 1, wherein said chemical receptor gene comprises substantially all species of olfactory receptor genes which are possessed by an animal selected from the group consisting of mice, humans, rats, dogs and cats.

14. The sensor according to claim 2, wherein said marker gene comprises G protein, said chemical receptor itself, or arrestin.

15. The sensor according to claim 2, wherein said marker gene comprises Gα

gene.

16. The sensor according to claim 2, wherein said marker gene comprises Gα

15, Gα

q or Gα

olf gene.

17. The sensor according to claim 2, wherein said marker gene comprises Gα

gene, Gβ

gene and Gγ

gene.

18. The sensor according to claim 1, wherein said support comprises solid support.

19. The sensor according to claim 1, wherein the support comprises a material selected from the group consisting of glass, silicon, silica, polystyrene and polymer films, which is coated or non-coated.

20. The sensor according to claim 1, wherein the signal comprises an agent selected from the group consisting of intracellular calcium concentration, inositol triphosphate, cyclicAMP, diacyl glycerol, cyclic GMP and cellular membrane potential.

21. The sensor according to claim 1, wherein the signal is intracellular calcium concentration, and said means for measuring the signal comprises a means for electronically, chemically or biologically measuring calcium concentration.

22. The sensor according to claim 2, wherein the marker gene is different from the genes which originally exist in said cell.

23. The sensor according to claim 1, wherein the cell comprises a cell selected from the group consisting of HEK 293 cell, CHO cell, COS-7 cell, neuroblastoma and NG108-15.

24. The sensor according to claim 1, wherein the cell substantially comprises one type of cell.

25. The sensor according to claim 5, wherein the olfactory receptor gene is different from the genes which originally exist in said cell.

26. The sensor according to claim 1, wherein the support comprises a cellular adhesion molecule.

27. The sensor according to claim 16, wherein the cellular adhesion molecule comprises fibronectin, vitronectin, or laminin, or a fragment or variant thereof.

28. The sensor according to claim 1, wherein the nucleic acid molecule or cell on said support is arranged thereon in an array format.

29. The sensor according to claim 28, wherein the arrayed region has an area of about 200 mm² or less.

30. The sensor according to claim 28, wherein the arrayed region has about 15 mm or less in length in the longitudinal direction.

31. The sensor according to claim 1 further comprising liquid sufficient for covering the cell.

32. The sensor according to claim 1 further comprising a medium for maintaining a cell.

33. The sensor according to claim 32, wherein the medium is a liquid medium.

34. The sensor according to claim 1, wherein said d) means for providing information comprises:

d-1) a signal processing member for using a stimulus species categorizing method based on a stimulus element tuning specificity of a cell having a chemical receptor to add a first signal output by predetermined plurality of said sensors, to calculate a value of sensory elemental information expressing a sensation, and outputting a calculation result as a second signal; and

d-2) an evaluation member for effecting qualitative and/or quantitative evaluation using the second signal output by the signal processing member.

35. The sensor according to claim 34, wherein the subqualities of sensation to the stimulus categorizing method uses classification according to species of the chemical receptor.

36. The sensor according to claim 34, wherein said signal processing member reduces, when one of first signals output by the plurality of sensors exceeds a predetermined value, the first signal output by a sensor different from the sensor and uses the reduced signal for producing the second signal.

37. The sensor according to claim 34, wherein the signal processing member comprises:

a plurality of selection members and addition members corresponding to sensory elemental information;

a plurality of amplification members corresponding to each of the sensors;

a coefficient calculation member for controlling the amplification member, wherein

the selection members multiply a plurality of the first signal with the coefficient designated by each of the sensors to produce a plurality of third signals;

the addition members add the plurality of third signals output by the corresponding selection member to produce a plurality of fourth signal;

the coefficient calculation member detects the maximum value among the plurality of fourth signals and normalizes each of the fourth signals using the maximum value to calculate control signals;

the amplification members use the corresponding control signals to produce the second signals corresponding to the intensity of sensory elemental information.

38. The sensor according to claim 37, wherein when a stimulus is presented, the first signal output by the sensor, is transiently produced directed to a predetermined value corresponding to the intensity or concentration of the stimulus from zero level, wherein the zero level is set as a status where no response is found in response to no stimuli;

the third signal is transiently produced associated therewith directing to a predetermined value corresponding to the intensity or concentration of a stimulus from zero level;

the coefficient calculation member determines a sensor response starting at base time when one of the first signals is determined to be the signal output in response to a stimulus by the sensor for the first time, and

calculates at a predetermined time as an elapsed time from the base time, the control signal for controlling the amplification member using the third signal at the predetermined time;

controls the amplification member using the control signal which was calculated at the last time until a control signal is calculated at the predetermined time.

39. The sensor according to claim 34, wherein when a stimulus is presented, the first signal output by the sensor, is transiently produced directed to a predetermined value corresponding to the intensity or concentration of the stimulus from zero level, wherein the zero level is set as a status where no response is found in response to no stimuli;

the third signal is transiently produced associated therewith directing to a predetermined value corresponding to the intensity or concentration of a stimulus from zero level;

the coefficient calculation member determines a sensor response starting at base time when one of the first signals is determined to be the signal output in response to a stimulus by the sensor for the first time;

during a period of time when the predetermined number of the plurality of third signals changes from augmentation to reduction,

calculates, at each time when the third signal is determined to start occurring significant output as a corresponding sense element, and when the third signal is determined to have achieved a plurality of boundary values which divide the section between the significant output value and the maximum value preset to the third signal into a plurality of segments;

controls the amplification member using the control signal which was calculated for the last time until the control signal is calculated.

40. A chip for use in a chemical sensor comprising:

a) a nucleic acid molecule comprising a base sequence encoding a chemical receptor gene; and

b) a support having a cell thereon arranged with the nucleic acid molecule introduced therein.

41. The chip according to claim 40, wherein the nucleic acid molecule further comprises a sequence encoding a marker gene.

42. The chip according to claim 40, further comprising means for transmitting a signal derived from the chemical receptor gene.

43. The chip according to claim 40, wherein the chemical receptor comprises a receptor selected from the group consisting of intranuclear receptors, cytoplasmic receptors and cellular membrane receptors.

44. The chip according to claim 40, wherein the chemical receptor comprises a receptor selected from the group consisting of G-protein coupled receptors, kinase-type receptors, ion-channel type receptors, intranuclear receptors, hormone receptors, chemokine receptors, and cytokine receptors.

45. The chip according to claim 40 wherein the chemical receptor comprises an olfactory receptor.

46. The chip according to claim 40, wherein the chemical receptor gene comprises a receptor selected from the group consisting of retinoic acid receptors, EGF receptors, interleukin receptors and CSF receptors.

47. The chip according to claim 40, wherein the chemical receptor gene comprises a nucleic acid sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO:

1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94 and 96, or a variant or fragment thereof.

48. The chip according to claim 40, wherein the chemical receptor gene comprises at least about two species.

49. The chip according to claim 40, wherein the chemical receptor gene comprises at least about ten species.

50. The chip according to claim 40, wherein the chemical receptor gene comprises at least about twenty species.

51. The chip according to claim 40, wherein the chemical receptor gene comprises at least about three hundred species.

52. The chip according to claim 40, wherein the chemical receptor gene comprises all species of chemical receptor genes which are possessed by an animal selected from the group consisting of mice, humans, rats, dogs and cats.

53. The chip according to claim 40, wherein the chemical receptor gene comprises substantially all species of olfactory receptor genes which are possessed by an animal selected from the group consisting of mice, humans, rats, dogs and cats.

54. The chip according to claim 41, wherein the marker gene comprises Gα

gene, the chemical receptor itself, or arrestin.

55. The chip according to claim 41, wherein the marker gene comprises a Gα

gene.

56. The chip according to claim 41, wherein the marker gene comprises Gα

15, Gα

q or Gα

olf.

57. The chip according to claim 41, wherein the marker gene comprises Gα

gene, Gβ

gene and Gγ

gene.

58. The chip according to claim 40, wherein the support comprises a solid support.

59. The chip according to claim 40, wherein the support comprises material selected from the group consisting of coated or non-coated glass, silicon, silica, polystyrene and polymer film.

60. The chip according to claim 41, wherein a signal produced by the marker gene comprises an agent selected from the group consisting of intracellular calcium concentration, inositol triphosphate, cyclic AMP, diacylglycerol, cyclic GMP and cell membrane potential.

61. The chip according to claim 41, wherein the marker gene is different from any genes already present in the cell.

62. The chip according to claim 40, wherein the cell comprises a cell consisting of HEK293 cell, CHO cell, COS-7 cell, neiuroblastoma and NG108-15 cell.

63. The chip according to claim 41, wherein the support comprises a connecting point for transmitting a signal derived from the marker.

64. The chip according to claim 40, wherein the support comprises a connecting point capable of transmitting at least one signal selected from the group consisting of an electrical signal, chemical signal and biological signal.

65. The chip according to claim 45, wherein the olfactory receptor gene is different from any genes already present in the cell.

66. The chip according to claim 40, wherein the support comprises a cellular adhesion molecule.

67. The chip according to claim 66, wherein the cellular adhesion molecule comprises fibronectin, vitronectin or laminin, or a fragment or a variant thereof.

68. The chip according to claim 40, wherein the nucleic acid molecule or cell on said support is arranged thereon in an array format.

69. The chip according to claim 68, wherein the arrayed region has an area of about 200 mm² or less.

70. The chip according to claim 68, wherein the arrayed region has a length of about 15 mm or less in the longitudinal direction.

71. The chip according to claim 40, further comprising a liquid sufficient for covering the cell.

72. The chip according to claim 40, further comprising a medium for maintaining the cell.

73. The chip according to claim 72, wherein the medium is a liquid medium.

74. A method for obtaining information relating to a chemical in a sample, comprising the steps of:

A) providing a cell having a nucleic acid molecule introduced therein, wherein the nucleic acid molecule comprises a sequence encoding a chemical receptor gene;

B) providing the cell with a sample comprising or suspected to comprise a chemical of interest;

C) measuring a change induced by the chemical in a signal derived from the chemical receptor gene in the cell; and

D) calculating a level of activation of the chemical receptor from the change in intensity of the measured signal to provide information on the chemical.

75. The method according to claim 74, wherein the nucleic acid molecule further comprises a sequence encoding a marker gene.

76. The method according to claim 74, wherein the chemical is a source of olfaction.

77. The method according to claim 74, wherein the chemical receptor gene comprises an olfactory receptor.

78. The method according to claim 74, wherein the chemical receptor gene comprises at least about two species.

79. The method according to claim 74, wherein the chemical receptor gene comprises at least about ten species.

80. The method according to claim 74, wherein the chemical receptor gene comprises at least about twenty species.

81. The method according to claim 74, wherein the chemical receptor gene comprises at least about three hundred species.

82. The method according to claim 74, wherein the chemical receptor gene comprises all species of chemical receptor genes which are possessed by an animal selected from the group consisting of mice, humans, rats, dogs and cats.

83. The method according to claim 75, wherein the marker gene comprises G protein-coupled protein.

84. The method according to claim 75, wherein the marker gene comprises Gα

gene, the chemical receptor itself, or arrestin.

85. The method according to claim 75, wherein the marker gene comprises Gα

15, Gα

q or Gα

olf.

86. The method according to claim 75, wherein the marker gene comprises Gα

gene, Gβ

gene and Gγ

gene.

87. The method according of claim 74 wherein the cell is fixed on a support.

88. The method according to claim 87, wherein the support comprises a solid support.

89. The method according to claim 74, wherein the support comprises material selected from the group consisting of coated or non-coated glass, silicon, silica, polystyrene and polymer film.

90. The method according to claim 75, wherein a signal produced by the marker gene comprises an agent selected from the group consisting of intracellular calcium concentration, inositol triphosphate, cyclic AMP, diacylglycerol, cyclic GMP and cell membrane potential.

91. The method according to claim 75, wherein the marker gene is different from any genes already present in the cell.

92. The method according to claim 74, wherein the cell comprises a cell consisting of HEK293 cell, CHO cell, COS-7 cell, neiuroblastoma and NG108-15 cell.

93. The method according to claim 74, wherein the olfactory receptor gene is different from any genes already present in the cell.

94. The method according to claim 74, wherein the support comprises a cellular adhesion molecule.

95. The method according to claim 94, wherein the cellular adhesion molecule comprises fibronectin, vitronectin or laminin, or a fragment or a variant thereof.

96. The method according to claim 74, wherein the information regarding the signal comprises change in level of an agent selected from the group consisting of intracellular calcium concentration, inositol triphosphate, cyclic AMP, diacylglycerol, cyclic GMP and cell membrane potential.

97. The method according to claim96, wherein the information is presented at real time.

98. The method according to claim 74, wherein the step B) comprises a step of providing the cell with the sample at a flow rate of about 1-4 mm/second.

99. The method according to claim 74, wherein the step B) comprises a step of providing the cell with the sample at a flow rate of about 2-3 mm/second.

100. The method according to claim 74, wherein the cell is provided with a liquid sufficient for covering the cell, and the step of B) comprises a step of providing the sample into the liquid.

101. The method according to claim 74, wherein further the cell is provided with a medium for maintaining the cell.

102. The method according to claim 101, wherein said medium comprises a liquid medium.

103. The method according to claim 87, wherein the nucleic acid molecule or cell on said support is arranged thereon in an array format.

104. The method according to claim 74, further comprising the step of correlating the information on the chemical with the information on the sample comprising or suspected to comprise the chemical of interest.

105. A sensation-evaluation system for evaluating sensation arising from a stimulant using output signal of a sensor comprising:

A) a plurality of sensors having different response characteristics from each other against stimuli from outside;

B) a signal processing member for using a stimulus species categorizing method based on a stimulus element tuning specificity of a cell having a chemical receptor to add a first signal output by predetermined plurality of said sensors, to calculate a value of sensory elemental information expressing a sensation, and outputting a calculation result as a second signal; and

C) an evaluation member for effecting qualitative and/or quantitative evaluation using the second signal output by the signal processing member.

106. The sensor evaluation system according to claim 105, wherein the cell is transfected with a nucleic acid molecule comprising a nucleic acid sequence encoding said chemical receptor.

107. The sensation-evaluation system according to claim 105, wherein said signal processing member reduces, when one of first signals output by the plurality of sensors exceeds a predetermined value, the first signal output by a sensor different from the sensor and uses the reduced signal for producing the second signal.

108. The sensation-evaluation system according to claim 105, wherein the signal processing member comprises:

a plurality of selection members and addition members corresponding to sensory elemental information;

a plurality of amplification members corresponding to each of the sensors;

a coefficient calculation member for controlling the amplification member, and wherein

the selection members multiply a plurality of the first signal with the coefficient designated by each of the sensors to produce a plurality of third signals;

the addition members add the plurality of third signals output by the corresponding selection member to produce a plurality of fourth signal;

the coefficient calculation member detects the maximum value among the plurality of fourth signals and normalizes each of the fourth signals using the maximum value to calculate control signals; and

the amplification members use the corresponding control signals to produce the second signals corresponding to the intensity of sensory elemental information.

109. The sensation-evaluation system according to claim 105, wherein when a stimulus is presented, the first signal output by the sensor, is transiently produced directed to a predetermined value corresponding to the intensity or concentration of the stimulus from zero level, wherein the zero level is set as a status where no response is found in response to no stimuli;

the third signal is transiently produced associated therewith directing to a predetermined value corresponding to the intensity or concentration of a stimulus from zero level;

the coefficient calculation member determines a sensor response starting at base time when one of the first signals is determined to be the signal output in response to a stimulus by the sensor for the first time; and

calculates at a predetermined time as an elapsed time from the base time, the control signal for controlling the amplification member using the third signal at the predetermined time;

controls the amplification member using the control signal which was calculated at the last time until a control signal is calculated at the predetermined time.

110. The sensation-evaluation system according to claim 108, wherein when a stimulus is presented, the first signal output by the sensors, is transiently produced directed to a predetermined value corresponding to the intensity or concentration of the stimulus from zero level, wherein the zero level is set as a status where no response is found in response to no stimuli;

the third signal is transiently produced associated therewith directing to a predetermined value corresponding to the intensity or concentration of a stimulus from zero level;

the coefficient calculation member determines a sensor response starting at base time when one of the first signals is determined to be the signal output in response to a stimulus by the sensor for the first time;

during a period of time when the predetermined number of the plurality of third signals change from augmentation to reduction,

calculates, at each time when the third signal is determined to start occurring significant output as a corresponding sense element, and when the third signal is determined to have achieved a plurality of boundary values which divide the section between the significant output value and the maximum value preset to the third signal into a plurality of segments;

controls the amplification member using the control signal which was calculated for the last time until the control signal is calculated, wherein when a stimulus is presented, the first signal output by the sensor, is transiently produced directed to a predetermined value corresponding to the intensity or concentration of the stimulus from zero level, wherein the zero level is set as a status where no response is found in response to no stimuli;

the third signal is transiently produced associated therewith directing to a predetermined value corresponding to the intensity or concentration of a stimulus from zero level;

the coefficient calculation member determines a sensor response starting base time when one of the first signals is determined to be the signal output in response to a stimulus by the sensor for the first time;

during a period of time when the predetermined number of the plurality of third signals change from augmentation to reduction,

calculates, at each time when the third signal is determined to start occurring significant output as a corresponding sense element, and when the third signal is determined to have achieved a plurality of boundary values which divide the section between the significant output value and the maximum value preset to the third signal into a plurality of segments;

controls the amplification member using the control signal which was calculated for the last time until the control signal is calculated.

111. The sensation-evaluation system according to claim 105, wherein the chemical receptor is an olfactory receptor;

and

the sensor is a sensor responding to an olfactory stimulus.

112. A method for evaluating a sense in a sensation-evaluation system for evaluating sensation arising from a stimulus using output signals of a sensor comprising a plurality of sensors having different response characteristics from each other against stimuli from outside and a signal processing member for processing an output signal from the sensors, comprising the steps of:

the first step wherein the signal processing member for using a stimulus species categorizing method based on a stimulus element tuning specificity of a cell having a chemical receptor to add a first signal output by predetermined plurality of said sensors, to calculate a value of sensory elemental information expressing a sensation, and outputting a calculation result as a second signal;

the second step wherein an evaluation member for effecting qualitative and/or quantitative evaluation using the second signal output by the signal processing member.

113. The method according to claim 112, wherein the cell is transfected with a nucleic acid molecule comprising a nucleic acid sequence encoding said chemical receptor.

114. The method according to claim 112, further comprising the third step wherein in the first step, said signal processing member reduces, when one of first signals output by the plurality of sensors exceeds a predetermined value, the first signal output by a sensor different from the sensor and uses the reduced signal for producing the second signal.

115. The method according to claim 112, wherein the signal processing member comprises:

a plurality of selection members and addition members corresponding to sensory elemental information;

a plurality of amplification members corresponding to each of the sensor;

coefficient calculation member for controlling the amplification member, the first step further comprising the fourth step wherein the selection members multiplies a plurality of the first signal with the coefficient designated by each of the sensors to produce a plurality of third signals;

the fifth step wherein the addition members add the plurality of third signals output by the corresponding selection member to produce a plurality of fourth signal;

the sixth step wherein the coefficient calculation member detects the maximum value among the plurality of fourth signals and normalizes each of the fourth signals using the maximum value to calculate control signals; and

the seventh step wherein the amplification members use the corresponding control signals to produce the second signals corresponding to the intensity of sensory elemental information.

116. The method according to claim 114, wherein when a stimulus is presented, the first signal output by the sensor, is transiently produced directed to a predetermined value corresponding to the intensity or concentration of the stimulus from zero level, wherein the zero level is set as a status where no response is found in response to no stimuli and the signal produced by the fourth step is transiently produced associated therewith directing to a predetermined value corresponding to the intensity or concentration of a stimulus from zero level;

the method further comprises the eighth step wherein in the sixth step, the coefficient calculation member determines a sensor response starting at base time when one of the first signals is determined to be the signal output in response to a stimulus by the sensor for the first time, and

calculates at a predetermined time as an elapsed time from the base time, the control signal for controlling the amplification member using the signal produced by the fifth step at the predetermined time, and

controls the amplification member using the control signal which was calculated at the last time until a control signal is calculated at the predetermined time.

117. The method according to claim 114, wherein when a stimulus is presented, the first signal output by the sensor, is transiently produced directed to a predetermined value corresponding to the intensity or concentration of the stimulus from zero level, wherein the zero level is set as a status where no response is found in response to no stimuli and the signal produced by the fourth step is transiently produced associated therewith directing to a predetermined value corresponding to the intensity or concentration of a stimulus from zero level;

the method further comprising the eighth step wherein in the sixth step, the coefficient calculation member determines a sensor response starting at base time when one of the first signals is determined to be the signal output in response to a stimulus by the sensor for the first time;

during a period of time when the predetermined number of the plurality of signals produced by the fifth step change from augmentation to reduction,

calculates, at each time when the signal produced by the fifth step is determined to start occurring significant output as a corresponding sense element, and when the signal produced by the fifth step is determined to have achieved a plurality of boundary values which divide the section between the significant output value and the maximum value preset to the signal produced by the fifth step into a plurality of segments;

controls the amplification member using the control signal which was calculated for the last time until the control signal is calculated.

118. The method according to claim 112, wherein

the chemical receptor is an olfactory receptor;

and

the sensor is a sensor responding to an olfactory stimulus.

119. A method for formulating a stimulant, comprising the steps of:

the first step of evaluating a predetermined stimulant using a sensation-evaluation system for evaluating sensation arising from a stimulant using output signal of a sensor comprising;

A-1) a plurality of sensors having different response characteristics from each other against stimuli from outside;

A-2) a signal processing member for using a stimulus species categorizing method based on a stimulus element tuning specificity of a cell having a chemical receptor to add a first signal output by predetermined plurality of said sensors, to calculate a value of sensory elemental information expressing a sensation, and outputting a calculation result as a second signal; and

A-3) an evaluation member for effecting qualitative and/or quantitative evaluation using the second signal output by the signal processing member;

B) the second step of determining a ratio of stimulant elements to be mixed corresponding thereto using a result of evaluation corresponding to the stimulant elements obtained by the evaluation result of the first step and the sensation-evaluation system; and

C) the third step of mixing the determined stimulant elements at the determined ratio.

120. The method according to claim 119, further comprising:

the fourth step of evaluating the mixed stimulant in the third step using the sensation-evaluation system; and

the fifth the step of comparing the evaluation step of fourth step and the evaluation result of the first step to determine the ratio to be newly mixed corresponding the stimulant element.

121. A computer readable recording medium having a computer program recorded thereon for implementing a process in a computer in a sensation-evaluation system for evaluating sensation arising from a stimulant using the output signal of a sensor comprising a plurality of sensors having different response characteristics from each other against stimuli from outside and a signal processing member for processing output signals from the sensors, the process comprising the procedures of:

the first procedure wherein the signal processing member using a stimulus species categorizing method based on a stimulus element tuning specificity of a cell having a chemical receptor to add a first signal output by predetermined plurality of said sensors, to calculate a value of sensory elemental information expressing a sensation, and outputting a calculation result as a second signal;

the second procedure wherein an evaluation member for effecting qualitative and/or quantitative evaluation using the second signal output by the signal processing member.

122. A computer program for implementing a process in a computer in a sensation-evaluation system for evaluating sensation arising from a stimulant using output signal of a sensor comprising a plurality of sensors having different response characteristics from each other against stimuli from outside and a signal processing member for processing an output signal from the sensors, the process comprising the procedures of:

the first procedure wherein the signal processing member using a stimulus species categorizing method based on a stimulus element tuning specificity of a cell having a chemical receptor to add a first signal output by predetermined plurality of said sensors, to calculate a value of sensory elemental information expressing a sensation, and outputting a calculation result as a second signal;

the second procedure wherein an evaluation member for effecting qualitative and/or quantitative evaluation using the second signal output by the signal processing member.

123. A nucleic acid molecule comprising:

(a) a polynucleotide having a base sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

1, 3, 5, 7, 9, 11, 13, 15, 17, 19and21, or a sequence fragment thereof;

(b) a polynucleotide encoding a polypeptide consisting of an amino acid sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22, or a fragment thereof;

(c) a polynucleotide encoding a variant polypeptide having an amino acid sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22, having at least one mutation selected from the group consisting of at least one amino acid substitution, addition and deletion, and having biological activity;

(d) a polynucleotide which is an allelic variant of DNA consisting of a base sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21;

(e) a polynucleotide encoding a species homolog of a polypeptide consisting of an amino acid sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22;

(f) a polynucleotide encoding a polypeptide hybridizable to any one of the polynucleotides (a) to (e) under stringent conditions, and having biological activity;

or

(g) a polynucleotide consisting of a base sequence having at least 70% identity to any one of the polynucleotides (a) to (e) or a complementary sequence thereof, and having biological activity.

124. The nucleic acid molecule according to claim 123, wherein the biological activity comprises a signal transduction activity of a chemical.

127. Use of the nucleic acid molecule according to claim 123 or the polypeptide according to claim 125 for detecting a chemical.

125. A polypeptide comprising:

(a) a polypeptide encoded by polynucleotide of a nucleic acid sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21, or a fragment thereof

(b) a polypeptide consisting of an amino acid sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22, or a fragment thereof;

(c) a polypeptide comprising an amino acid sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22, having at least one mutation selected from at least one amino acid substitution, addition and deletion, and having biological activity;

(d) a polypeptide encoded by an allelic variant of a base sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21;

(e) a polypeptide which is a species homolog of an amino acid sequence set forth in SEQ ID NO. selected from the group consisting of SEQ ID NO;

2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 22;

or

(f) a polypeptide having an amino acid sequence having at least 70% identity to any one of the polypeptides (a) to (e), and having biological activity.

126. The polypeptide according to claim 125, wherein said biological activity comprises signal transduction activity of a chemical.