System and method for diagnosis of disease by infrared analysis of human tissues and cells

• US 5,733,739 A
• Filed: 06/07/1995
• Issued: 03/31/1998
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Inphocyte, Inc.
• Original Assignee: Inphocyte, Inc.
• Inventors: Lord, John B., Zakim, David S.
• Primary Examiner(s): LEARY, LOUISE N
• Application Number:
  US08/523,972
• Time in Patent Office: 1,028 Days
• Field of Search: 435/29, 435/40.51, 435/40.5, 435/34, 435/968, 435/4, 435/366, 435/373, 435/374, 436/63, 436/171, 436/173, 436/174, 250/338.1, 250/472.1, 250/281, 356/300, 356/326, 128/664
• US Class Current: 435/29
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: Y10S 435/968 High energy substrates, e.g. fluorescent, chemiluminescent, radioactive
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
• CPC Class Codes: Y10T 436/25 including sample preparation

Abstract

A machine-based method for collecting and interpreting quantitative data on cells and tissues so that a diagnosis will obtain as to the existence or non-existence of disease in an human. Vibrational spectroscopy is used and the spectra generated by such spectroscopy are compared with stored spectra to provide whether cells or tissues are diseased, and if diseased to what degree. It, therefore, is possible to provide a basis for immediate diagnostic decisions for patients and physicians, leading in turn to immediate implementation of next-step procedures and treatment all in one visit to the doctor'"'"'s office. This means that patients and the examining clinician can know almost instantly whether or not the cells or tissue examined are normal or diseased, and the level of disease present if found. The advantages of bringing the diagnostic pathology service directly into the doctor'"'"'s office include immediate relief to the patient'"'"'s concern about health as well as immediate clarification of what needs to be done next in order to treat the disease that is present, and include any other actions that are necessary. The need for biopsies to obtain desired information on the existence or non-existence of disease is obviated. That is, them is a rapid identification of the area of tissue that is affected by disease prior to obtaining biopsies. This makes it possible to apply a single standard of diagnostic accuracy anywhere in the world, independent of the local availability of pathologists or other professionals.

Claims

1. A method for detecting and diagnosing disease in cells, comprising the steps of:

obtaining and storing in storage means first spectra in a predetermined frequency range for at least one cell that has been determined to be free of dysplasia;

collecting and distributing cells in a predetermined manner on a predetermined surface with cell collecting means;

generating second spectra with for at least one cell disposed on the predetermined surface with a spectrometer means;

comparing the first and second spectra for variations in frequency bands for indicating dysplasia;

diagnosing a level of dysplasia based on a number and magnitude of variations of the first and second spectra.

2. The method as recited in claim 1, wherein the collecting and distributing step includes collecting and distributing cells on a window of a sample holder.

3. The method as recited in claim 2, wherein the window and sample holder are transparent to infrared and Raman energies.

4. The method as recited in claim 1, wherein the generating step includes generating spectra based on vibrational spectroscopy.

5. The method as recited in claim 4, wherein the spectroscopy includes infrared spectroscopy.

6. A method for of detecting and diagnosing disease in epithelial cells, comprising the steps of:

(a) obtaining and storing in storage means first spectra in a mid-infrared frequency range for at least one cell from a patient being tested that has been determined to have a specific predetermined state;

(b) collecting cells from the patient being tested;

(c) generating second spectra in the mid-infrared frequency range from the cells collected at step (b);

(d) comparing the first and second spectra for variations caused by a predetermined condition; and

(e) diagnosing a change of levels of dysplasia based on the comparison at step (d) for determining a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

7. The method as recited in claim 6, wherein the mid-infrared frequency range is between 600-4000 cm^-1.

8. The method as recited in claim 6, wherein the collecting at step (b) is carried out by scraping.

9. The method as recited in claim 6, wherein the collecting at step (b) is carried out by surgical biopsy.

10. The method as recited in claim 6, wherein the collecting at step (b) is carried out by fine needle aspiration.

11. The method as recited in claim 6, wherein the collecting at step (b) is carried out by a collection of stool.

12. The method as recited in claim 6, wherein the collecting at step (b) is carried out by a collection of urine.

13. The method as recited in claim 6, wherein obtaining first spectra in step (a) is carried out using infrared transmission techniques.

14. The method as recited in claim 6, wherein obtaining first spectra in step (a) is carried out using infrared reflectance techniques.

15. The method as recited in claim 6, wherein obtaining first spectra in step (a) is carried out using infrared attenuated total reflectance (ATR) techniques.

16. The method as recited in claim 6, wherein obtaining first spectra in step (a) is carried out using multi-variable perturbation infrared techniques.

17. The method as recited in claim 6, wherein generating second spectra in step (c) is carried out using infrared transmission techniques.

18. The method as recited in claim 6, wherein generating second spectra in step (c) is carried out using infrared reflectance techniques.

19. The method as recited in claim 6, wherein generating second spectra in step (c) is carried out using infrared attenuated total reflectance (ATR) techniques.

20. The method as recited in claim 6, wherein generating second spectra in step (c) is carried out using multi-variable perturbation infrared techniques.

21. The method as recited in claim 6, wherein the method is used for detecting and diagnosing disease in epithelial cells in humans.

22. The method as recited in claim 6, wherein the method is used for detecting and diagnosing disease in epithelial cells in non-humans.

23. The method as recited in claim 22, wherein the method is used for detecting and diagnosing disease in epithelial cells in animals.

24. The method as recited in claim 6, wherein the method is used for detecting and diagnosing disease in epithelial cells in-vitro.

25. The method as recited in claim 6, wherein the specific predetermined state in step (a) is dysplasia.

26. The method as recited in claim 6, wherein the specific predetermined state in step (a) is non-dysplasia.

27. The method as recited in claim 6, wherein the specific predetermined state in step (a) is precancer.

28. The method as recited in claim 6, wherein the specific predetermined state in step (a) is frank cancer.

29. The method as recited in claim 6, wherein the predetermined condition in step (d) is dysplasia.

30. The method as recited in claim 6, wherein the predetermined condition in step (d) is inflammation.

31. The method as recited in claim 6, wherein the obtaining the first Raman spectra includes collecting said first spectra in-situ.

32. The method as recited in claim 31, wherein collecting said first spectra in-situ includes collecting with a sensing probe.

33. A method for detecting and diagnosing disease in epithelial cells of humans, comprising the steps of:

(a) obtaining and storing in storage means first spectra in a near-infrared frequency range for at least one cell from a patient being tested that has been determined to have a specific predetermined state;

(b) collecting cells from the patient being tested;

(c) generating second spectra in the near-infrared frequency range from the cells collected at step (b);

(d) comparing the first and second spectra for variations caused by a predetermined condition; and

(e) diagnosing a change of levels of dysplasia based on the comparison at step (d) for determining a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

34. The method as recited in claim 33, wherein the near-infrared frequency range is between 4000-10,000 cm^-1.

35. The method as recited in claim 33, wherein the collecting at step (b) may be carried out by scraping.

36. The method as recited in claim 33, wherein the collecting at step (b) is carrier out by surgical biopsy.

37. The method as recited in claim 33, wherein the collecting at step (b) is carried out by fine needle aspiration.

38. The method as recited in claim 33, wherein the collecting at step (b) is carried out by a collection of stool.

39. The method as recited in claim 33, wherein the collecting at step (b) is carried out by a collection of urine.

40. The method as recited in claim 33, wherein obtaining first spectra in step (a) is carried out using infrared transmission techniques.

41. The method as recited in claim 33, wherein obtaining first spectra in step (a) is carried out using infrared reflectance techniques.

42. The method as recited in claim 33, wherein obtaining first spectra in step (a) is carried out using infrared attenuated total reflectance (ATR) techniques.

43. The method as recited in claim 33, wherein obtaining first spectra in step (a) is carried out using multi-variable perturbation infrared techniques.

44. The method as recited in claim 33, wherein generating second spectra in step (c) is carried out using infrared transmission techniques.

45. The method as recited in claim 33, wherein generating second spectra in step (c) is carried out using infrared reflectance techniques.

46. The method as recited in claim 33, wherein generating second spectra in step (c) is carried out using infrared attenuated total reflectance (ATR) techniques.

47. The method as recited in claim 33, wherein generating second spectra in step (c) is carried out using multi-variable perturbation infrared techniques.

48. The method as recited in claim 33, wherein the method is used for detecting and diagnosing disease in epithelial cells in-vitro.

49. The method as recited in claim 33, wherein the specific predetermined state in step (a) is dysplasia.

50. The method as recited in claim 33, wherein the specific predetermined state in step (a) is non-dysplasia.

51. The method as recited in claim 33, wherein the specific predetermined state in step (a) is precancer.

52. The method as recited in claim 33, wherein the specific predetermined state in step (a) is frank cancer.

53. The method as recited in claim 33, wherein the predetermined condition in step (d) is dysplasia.

54. The method as recited in claim 33, wherein the predetermined condition in step (d) is inflammation.

55. The method as recited in claim 33, wherein the obtaining the first Raman spectra includes collecting said first spectra in-situ.

56. The method as recited in claim 55, wherein collecting said first spectra in-situ includes collecting with a sensing probe.

57. A method for of detecting and diagnosing disease in epithelial cells, comprising the steps of:

(a) obtaining and storing in storage means first Raman spectra for at least one cell from a patient being tested that has been determined to have a specific predetermined state;

(b) collecting cells from the patient being tested;

(c) generating second Raman spectra from the cells collected at step (b);

(d) comparing the first and second Raman spectra for variations caused by a predetermined condition; and

(e) diagnosing a change of levels of dysplasia based on the comparison at step (d) for determining a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

58. The method as recited in claim 57, wherein the collecting at step (b) is carrier out by scraping.

59. The method as recited in claim 57, wherein the collecting at step (b) is carried out by surgical biopsy.

60. The method as recited in claim 57, wherein the collecting at step (b) is carried out by fine needle aspiration.

61. The method as recited in claim 57, wherein the collecting at step (b) is carried out by a collection of stool.

62. The method as recited in claim 57, wherein the collecting at step (b) is carried out by a collection of urine.

63. The method as recited in claim 57, wherein the method is used for detecting and diagnosing disease in epithelial cells in humans.

64. The method as recited in claim 57, wherein the method is used for detecting and diagnosing disease in epithelial cells in non-humans.

65. The method as recited in claim 64, wherein the method is used for detecting and diagnosing disease in epithelial cells in animals.

66. The method as recited in claim 57, wherein the method is used for detecting and diagnosing disease in epithelial cells in-vitro.

67. The method as recited in claim 57, wherein the specific predetermined state in step (a) is dysplasia.

68. The method as recited in claim 57, wherein the specific predetermined state in step (a) is non-dysplasia.

69. The method as recited in claim 57, wherein the specific predetermined state in step (a) is precancer.

70. The method as recited in claim 57, wherein the specific predetermined state in step (a) is frank cancer.

71. The method as recited in claim 57, wherein the predetermined condition in step (d) is dysplasia.

72. The method as recited in claim 57, wherein the predetermined condition in step (d) is inflammation.

73. The method as recited in claim 57, wherein the frequency range of the Raman spectra is from ultraviolet to near-infrared.

74. The method as recited in claim 57, wherein the obtaining the first Raman spectra includes collecting said first spectra in-situ.

75. The method as recited in claim 74, wherein collecting said first spectra in-situ includes collecting with a sensing probe.

76. A method for of detecting and diagnosing disease in epithelial cells, comprising the steps of:

(a) obtaining and storing in storage means first resonance Raman spectra for at least one cell from a patient being tested that has been determined to have a specific predetermined state;

(b) collecting cells from the patient being tested;

(c) generating second Raman spectra from the cells collected at step (b);

(d) comparing the first and second resonance Raman spectra for variations caused by a predetermined condition; and

(e) diagnosing a change of levels of dysplasia based on the comparison at step (d) for determining a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

77. The method as recited in claim 76, wherein the collecting at step (b) is carried out by scraping.

78. The method as recited in claim 76, wherein the collecting at step (b) is carried out by surgical biopsy.

79. The method as recited in claim 76, wherein the collecting at step (b) is carried out by fine needle aspiration.

80. The method as recited in claim 76, wherein the collecting at step (b) is carried out by a collection of stool.

81. The method as recited in claim 76, wherein the collecting at step (b) is carried out by a collection of urine.

82. The method as recited in claim 76, wherein the method is used for detecting and diagnosing disease in epithelial cells in humans.

83. The method as recited in claim 76, wherein the method is used for detecting and diagnosing disease in epithelial cells in non-humans.

84. The method as recited in claim 83, wherein the method is used for detecting and diagnosing disease in epithelial cells in animals.

85. The method as recited in claim 76, wherein the method is used for detecting and diagnosing disease in epithelial cells in-vitro.

86. The method as recited in claim 76, wherein the specific predetermined state in step (a) is dysplasia.

87. The method as recited in claim 76, wherein the specific predetermined state in step (a) is non-dysplasia.

88. The method as recited in claim 76, wherein the specific predetermined state in step (a) is precancer.

89. The method as recited in claim 76, wherein the specific predetermined state in step (a) is frank cancer.

90. The method as recited in claim 76 wherein the predetermined condition in step (d) is dysplasia.

91. The method as recited in claim 76, wherein the predetermined condition in step (d) is inflammation.

92. The method as recited in claim 76, wherein the frequency range of the Raman spectra is from ultraviolet to near-infrared.

93. The method as recited in claim 76, wherein the obtaining the first Raman spectra includes collecting said first spectra in-situ.

94. The method as recited in claim 93, wherein collecting said first spectra in-situ includes collecting with a sensing probe.

95. A method for detecting and diagnosing disease in epithelial cells for grading on a continuous scale of a predetermined range from non-dysplastic to fully dysplastic, comprising the steps of:

(a) setting a first quantitative value along the continuous scale representative of a predetermined dysplastic condition for at least one cell of a patient being tested so that relative changes in a degree of dysplasia may be determined for said patient;

(b) collecting cells from the patient being tested;

(c) generating spectral information from the cells collected at step (b);

(d) determining a second quantitative value along the continuous scale that is representative of spectral information generated at step (c);

(e) comparing the first and second quantitative values on the continuous scale; and

(f) determining based on the first and second quantitative values a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

96. The method as recited in claim 95, wherein the method is used for detecting and diagnosing disease in epithelial cells in humans.

97. The method as recited in claim 95, wherein the method is used for detecting and diagnosing disease in epithelial cells in non-humans.

98. The method as recited in claim 97, wherein the method is used for detecting and diagnosing disease in epithelial cells in animals.

99. The method as recited in claim 98, wherein the method is used for detecting and diagnosing disease in epithelial cells in-vitro.

100. The method as recited in claim 95, wherein the collecting at step (b) is carried out by scraping.

101. The method as recited in claim 95, wherein the collecting at step (b) is carried out by surgical biopsy.

102. The method as recited in claim 95, wherein the collecting at step (b) is carried out by fine needle aspiration.

103. The method as recited in claim 98, wherein the collecting at step (b) is carried out by a collection of stool.

104. The method as recited in claim 98, wherein the collecting at step (b) is carried out by a collection of urine.

105. A method for detecting and diagnosing disease in epithelial cells for grading on a continuous scale of a predetermined range from non-dysplastic to fully dysplastic, comprising the steps of:

(a) setting a first quantitative value along the continuous scale representative of a predetermined dysplastic condition for at least one cell in a cell culture being tested so that relative changes in a degree of dysplasia may be determined for said cell culture;

(b) collecting cells from the cell culture being tested;

(c) generating spectral information from the cell collected at step (b);

(d) determining a second quantitative value along the continuous scale that is representative of spectral information generated at step (c);

(e) comparing the first and second quantitative values on the continuous scale; and

(f) determining based on the first and second quantitative values a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

106. The method as recited in claim 105, wherein the method is used for detecting and diagnosing disease in epithelial cells from humans.

107. The method as recited in claim 105, wherein the method is used for detecting and diagnosing disease in epithelial cells from non-humans.

108. The method as recited in claim 105, wherein the method is used for detecting and diagnosing disease in epithelial cells from animals.

109. The method as recited in claim 105, wherein the method is used for detecting and diagnosing disease in epithelial cells in-vitro.

110. The method as recited in claim 105, wherein the collecting at step (b) is carried out by scraping.

111. The method as recited in claim 105, wherein the collecting at step (b) is carried out by surgical biopsy.

112. The method as recited in claim 105, wherein the collecting at step (b) is carried out by fine needle aspiration.

113. The method as recited in claim 105, wherein the collecting at step (b) is carried out by a collection of stool.

114. The method as recited in claim 105, wherein the collecting at step (b) is carried out by a collection of urine.

115. A method for detecting and diagnosing disease in cells, comprising the steps of:

(a) obtaining first spectra in a predetermined frequency range for at least a first cell from a source;

(b) comparing the first spectra with a set of spectral data indicative of a plurality of states of dysplasia and determining a state of dysplasia for the first cell;

(c) collecting at least a second cell from the source;

(d) generating second spectra in a predetermined frequency range for the second cell;

(e) comparing the second spectra with the set of spectral data indicative of a plurality of states of dysplasia and determining a state of dysplasia for the second cell;

(f) comparing the state of dysplasia for the first cell and the state of dysplasia for the second cell; and

(g) diagnosing a change of levels of dysplasia based on the comparison at step (f) for determining a degree of progression or regression of dysplasia, or whether there have been no change in dysplasia.

116. The method as recited in claim 115, wherein the collecting step at step (c) is carried out by scraping.

117. The method as recited in claim 115, wherein the collecting step at step (c) is carried out by surgical biopsy.

118. The method as recited in claim 115, wherein the collecting step at step (c) is carried out by fine needle aspiration.

119. The method as recited in claim 115, wherein the collecting step at step (c) is carried out by a collection of stool.

120. The method as recited in claim 115, wherein the collecting step at step (c) is carried out by a collection of urine.

121. The method as recited in claim 115, wherein the method is used for detecting and diagnosing disease in humans.

122. The method as recited in claim 115, wherein the method is used for detecting and diagnosing disease in non-humans.

123. The method as recited in claim 115, wherein the method is used for detecting and diagnosing disease in animals.

124. The method as recited in claim 115, wherein obtaining first spectra in step (a) is carried out using infrared transmission techniques.

125. The method as recited in claim 115, wherein generating second spectra in step (d) is carried out using infrared transmission techniques.

126. A method for detecting and diagnosing disease in cells, comprising the steps of:

(a) obtaining and storing in storage means first spectra in at least one predetermined frequency range for at least a first cell from a source with the stored spectra being determined to have a specific state of dysplasia;

(b) collecting at least a second cell from the source;

(c) generating second spectra in at least one predetermined frequency range for the second cell collected at step (b);

(d) comparing the second spectra with a set of spectral data indicative of a plurality of states of dysplasia and determining a state of dysplasia for the second cell;

(e) comparing the state of dysplasia for the first cell with the state of dysplasia for the second cell; and

(f) diagnosing a change of levels of dysplasia based on the comparison at step (e) for determining a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

127. The method as recited in claim 126, wherein the collecting step at step (b) is carried out by scraping.

128. The method as recited in claim 126, wherein the collecting step at step (b) is carried out by surgical biopsy.

129. The method as recited in claim 126, wherein the collecting step at step (b) is carried out by fine needle aspiration.

130. The method as recited in claim 126, wherein the collecting step at step (b) is carried out by a collection of stool.

131. The method as recited in claim 126, wherein the collecting step at step (b) is carried out by a collection of urine.

132. The method as recited in claim 126, wherein the method is used for detecting and diagnosing disease in humans.

133. The method as recited in claim 126, wherein the method is used for detecting and diagnosing disease in non-humans.

134. The method as recited in claim 126, wherein the method is used for detecting and diagnosing disease in animals.

135. The method as recited in claim 126, Wherein obtaining first spectra in step (a) is carried out using infrared transmission techniques.

136. The method as recited in claim 126, wherein generating second spectra in step (c) is carried out using infrared transmission techniques.

137. A method for detecting and diagnosing disease in cells, comprising the steps of:

(a) obtaining and storing in storage means first spectra in a near-infrared frequency range for at least a first cell from a source with the stored spectra being determined to have a specific state of dysplasia;

(b) collecting at least a second cell from the source;

(c) generating second spectra in a near-infrared frequency range for the second cell collected at step (b);

(d) comparing the second spectra with a set of spectral data indicative of a plurality of states of dysplasia and determining a state of dysplasia for the second cell;

(e) comparing the state of dysplasia for the first cell with the state of dysplasia for the second cell; and

(f) diagnosing a change of levels of dysplasia based on the comparison at step (e) for determining a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

138. The method as recited in claim 137, wherein the collecting step at step (b) is carried out by scraping.

139. The method as recited in claim 137, wherein the collecting step at step (b) is carried out by surgical biopsy.

140. The method as recited in claim 137, wherein the collecting step at step (b) is carried out by fine needle aspiration.

141. The method as recited in claim 137, wherein the collecting step at step (b) is carried out by a collection of stool.

142. The method as recited in claim 137, wherein the collecting step at step (b) is carried out by a collection of urine.

143. The method as recited in claim 137, wherein the method is used for detecting and diagnosing disease in humans.

144. The method as recited in claim 137, wherein the method is used for detecting and diagnosing disease in non-humans.

145. The method as recited in claim 137, wherein the method is used for detecting and diagnosing disease in animals.

146. The method as recited in claim 137, wherein obtaining first spectra in step (a) is carried out using infrared transmission techniques.

147. The method as recited in claim 137, wherein generating second spectra in step (c) is carried out using infrared transmission techniques.

148. A method for detecting and diagnosing disease in cells, comprising the steps of:

(a) obtaining and storing in storage means first Raman spectra for at least a first cell from a source with the stored spectra being determined to have a specific state of dysplasia;

(b) collecting at least a second cell from the source;

(c) generating second Raman spectra for the second cell collected at step (b);

(d) comparing the second spectra with a set of spectral data indicative of a plurality of states of dysplasia and determining a state of dysplasia for the second cell;

(e) comparing the state of dysplasia for the first cell with the state of dysplasia for the second cell; and

(f) diagnosing a change of levels of dysplasia based on the comparison at step (e) for determining a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

149. The method as recited in claim 148, wherein the collecting step at step (b) is carried out by scraping.

150. The method as recited in claim 148, wherein the collecting step at step (b) is carried out by surgical biopsy.

151. The method as recited in claim 148, wherein the collecting step at step (b) is carried out by fine needle aspiration.

152. The method as recited in claim 148, wherein the collecting step at step (b) is carried out by a collection of stool.

153. The method as recited in claim 148, wherein the collecting step at step (b) is carried out by a collection of urine.

154. The method as recited in claim 148, wherein the method is used for detecting and diagnosing disease in humans.

155. The method as recited in claim 148, wherein the method is used for detecting and diagnosing disease in non-humans.

156. The method as recited in claim 148, wherein the method is used for detecting and diagnosing disease in animals.

157. The method as recited in claim 148, wherein obtaining first spectra in step (a) is carried out using Raman techniques.

158. The method as recited in claim 148, wherein generating second spectra in step (c) is carried out using Raman techniques.

159. A method for detecting and diagnosing disease in cells, comprising the steps of:

(a) obtaining and storing in storage means first resonance Raman spectra for at least a first cell from a source with the stored spectra being determined to have a specific state of dysplasia;

(b) collecting at least a second cell from the source;

(c) generating second resonance Raman spectra for the second cell collected at step (b);

(d) comparing the second spectra with a set of spectra data indicative of a plurality of states of dysplasia and determining a state of dysplasia for the second cell;

(e) comparing the state of dysplasia for the first cell with the state of dysplasia for the second cell; and

(f) diagnosing a change of levels of dysplasia based on the comparison at step (e) for determining a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

160. The method as recited in claim 159, wherein the collecting step at step (b) is carried out by scraping.

161. The method as recited in claim 159, wherein the collecting step at step (b) is carried out by surgical biopsy.

162. The method as recited in claim 159, wherein the collecting step at step (b) is carried out by fine needle aspiration.

163. The method as recited in claim 159, wherein the collecting step at step (b) is carried out by a collection of stool.

164. The method as recited in claim 159, wherein the collecting step at step (b) is carried out by a collection of urine.

165. The method as recited in claim 159, wherein the method is used for detecting and diagnosing disease in humans.

166. The method as recited in claim 159, wherein the method is used for detecting and diagnosing disease in non-humans.

167. The method as recited in claim 159, wherein the method is used for detecting and diagnosing disease in animals.

168. The method as recited in claim 159, wherein obtaining first spectra in step (a) is carried out using resonance Raman techniques.

169. The method as recited in claim 159, wherein generating second spectra in step (c) is carried out using resonance Raman techniques.

170. A method for detecting and diagnosing disease in cells for grading on a continuous scale of a predetermined range from non-dysplastic to fully dysplastic, comprising the steps of:

(a) setting a first quantitative value along the continuous scale representative of a predetermined dysplastic condition for at least one cell of a source so that relative changes in a degree of dysplasia may be determined for the source;

(b) collecting cells from the source;

(c) generating spectral information from the cells collected at step (b);

(d) determining a second quantitative value along the continuous scale that is representative of spectral information generated at step (c);

(e) comparing the first and second quantitative values on the continuous scale; and

(f) determining based on the first and second quantitative values a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

171. The method as recited in claim 170, wherein the collecting step at step (b) is carried out by scraping.

172. The method as recited in claim 170, wherein the collecting step at step (b) is carried out by surgical biopsy.

173. The method as recited in claim 170, wherein the collecting step at step (b) is carried out by fine needle aspiration.

174. The method as recited in claim 170, wherein the collecting step at step (b) is carried out by a collection of stool.

175. The method as recited in claim 170, wherein the collecting step at step (b) is carried out by a collection of urine.

176. The method as recited in claim 170, wherein the method is used for detecting and diagnosing disease in humans.

177. The method as recited in claim 170, wherein the method is used for detecting and diagnosing disease in non-humans.

178. The method as recited in claim 170, wherein the method is used for detecting and diagnosing disease in animals.

179. The method as recited in claim 170, generating spectral information in step (c) is carried out using infrared transmission techniques.

180. A method for detecting and diagnosing disease in cells for grading on a continuous scale of a predetermined range from non-dysplastic to fully dysplastic, comprising the steps of:

(a) setting a first quantitative value along the continuous scale representative of a predetermined dysplastic condition for at least one cell in a cell culture so that relative changes in a degree of dysplasia may be determined for the source;

(b) collecting cells from the source;

(c) generating spectral information from the cells collected at step (b);

(d) determining a second quantitative value along the continuous scale that is representative of spectral information generated at step (c);

(e) comparing the first and second quantitative values on the continuous scale; and

(f) determining based on the first and second quantitative values a degree of progression or regression of dysplasia, or whether there has been no change in dysplasia.

181. The method as recited in claim 180, wherein the collecting step at step (b) is carried out by scraping.

182. The method as recited in claim 180, wherein the collecting step at step (b) is carried out by surgical biopsy.

183. The method as recited in claim 180, wherein the collecting step at step (b) is carried out by fine needle aspiration.

184. The method as recited in claim 180, wherein the collecting step at step (b) is carried out by a collection of stool.

185. The method as recited in claim 180, wherein the collecting step at step (b) is carried out by a collection of urine.

186. The method as recited in claim 180, wherein the method is used for detecting and diagnosing disease in humans.

187. The method as recited in claim 180, wherein the method is used for detecting and diagnosing disease in non-humans.

188. The method as recited in claim 180, wherein the method is used for detecting and diagnosing disease in animals.

189. The method as recited in claim 180, generating spectral information in step (c) is carried out using infrared transmission techniques.