Breath test apparatus and methods

• US 20030216660A1
• Filed: 06/10/2003
• Published: 11/20/2003
• Est. Priority Date: 06/08/1999
• Status: Active Grant

• Current Assignee: Oridion Medical (1987) Ltd. (Medtronic Plc)
• Original Assignee: Boaz Givron, Daniel Katzman, Ephraim Carlebach, Gershon Levitsky, Ilan Ben Oren, Julian Daich, Lewis Colman
• Inventors: Ben-Oren, Ilan, Carlebach, Ephraim, Daich, Julian, Levitsky, Gershon, Colman, Lewis, Givron, Boaz, Katzman, Daniel
• Granted Patent: US 7,488,229 B2
• Time in Patent Office: Days
• US Class Current: 600/532
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 5/083 Measuring rate of metabolism by using breath test, e.g. measuring rate of oxygen consumption
• CPC Class Codes: A61B 5/0836 Measuring rate of CO2 production
• CPC Class Codes: A61B 5/097 Devices for facilitating collection of breath or for directing breath into or through measuring devices
• CPC Class Codes: G01N 33/0006 Calibrating gas analysers
• CPC Class Codes: G01N 33/497 of gaseous biological material, e.g. breath
• CPC Class Codes: H01J 61/14 having one or more carbon compounds as the principal constituents
• CPC Class Codes: H01J 61/35 provided with coatings on the walls thereof; Selection of materials for the coatings using coloured coatings H01J61/40; using luminescent coatings H01J61/42
• CPC Class Codes: H01J 65/042 by an external electromagnetic field
• CPC Class Codes: H01J 9/247 specially adapted for gas-discharge lamps

Abstract

Breath test methods and apparatus for increasing accuracy and reducing the time taken to achieve diagnostically useful results. In order to determine when an increase in isotopic ratio of the exhaled breath is clinically significant, methods are described for the use of a variable and multiple threshold level; for reducing the time taken to determine an accurate baseline level; and for avoiding the effects of oral activity when making measurements. To increase measurement accuracy, methods are described, using the results of the breath tests themselves, of continuous and automatic self-calibration to correct for drifts in the gas spectrometer absorption curves. A method for increasing the spectral stability of cold cathode discharge infra-red light sources for use in breath test instrumentation is described. Calibration checking devices and methods of mandating their use at regular time intervals are described, to ensure maintenance of the accuracy of breath tests.

Claims

1. A method of determining in a breath test, when a change in a measurement of an isotopic ratio of at least one breath sample of a subject is clinically significant, wherein the criterion for said determining varies during said breath test.

2. The method according to claim 1 and wherein said measurement comprises the deviation of said isotopic ratio from a measurement of at least one previous sample of said subject.

3. The method according to claim 2 and wherein said measurement of at least one previous sample of said subject is a baseline measurement.

4. The method according to claim 1 and wherein said measurement comprises the rate of change of said isotopic ratio.

5. The method according to claim 1 and wherein said criterion is a function of elapsed time of the test.

6. The method according to claim 1 and wherein said criterion is a function of the noise level of the instrument performing said test.

7. The method according to claim 1 and wherein said criterion is a function of the physiological results of said test.

18. The method according to claim 1 and wherein said measurement of an isotopic ratio of at least one breath sample is performed only after significant subsidence of oral activity.

8. A breath test method using at least one threshold level for determining when the isotopic ratio of at least one breath sample shows sufficient deviation from a measurement of the isotopic ratio of at least one previous sample, that a clinically significant result of the breath test may be concluded, wherein said at least one threshold shows variation during said breath test.

9. The method according to claim 8 and wherein said measurement of at least one previous sample of said subject is a baseline measurement.

10. The method according to claim 8 and wherein said variation is at least a function of the elapsed time from ingestion of an identifying substrate by a subject.

11. The method according to claim 8 and wherein said variation is at least a function of the physiological results of the analysis of at least one of said samples.

12. The method according to claim 8 and wherein said variation is at least a function of the nature of the results obtained in said breath test.

13. The method according to claim 12 and wherein said nature of the results is at least a function of the standard deviation of the spread of results in said breath test.

14. The method according to claim 12 and wherein said nature of the results is at least a function of the noise level present in said results.

15. The method according to claim 12 and wherein said nature of the results is at least a function of the instrumental drift present in said results.

16. The method according to claim 8 and wherein said variation covers a range of values between an upper threshold and a lower threshold.

17. The method according to claim 16 and wherein said upper threshold and said lower threshold converge as the test proceeds.

19. The method according to claim 16 and wherein the presence of at least two measurements above said upper threshold within a predetermined time is indicative of a positive result of said breath test.

20. The method according to claim 16 and wherein the presence of at least two successive measurements above said upper threshold is indicative of a positive result of said breath test.

21. The method according to claim 16 and wherein the presence of at least two measurements above said upper threshold in combination with the absence of measurements below said lower threshold is indicative of a positive result of said breath test.

22. The method according to claim 16 and wherein the presence of at least two measurements below said lower threshold within a predetermined time is indicative of a negative result of said breath test.

23. The method according to claim 16 and wherein the presence of at least two successive measurements below said lower threshold is indicative of a negative result of said breath test.

24. The method according to claim 16 and wherein the presence of at least two measurements below said lower threshold in combination with the absence of any measurements above said upper threshold is indicative of a negative result of said breath test.

25. The method according to claim 16 and wherein the presence of at least two successive measurements falling below the upper threshold, with less than a predetermined difference in the value of delta between said three measurements, and with less than a predetermined average slope between them, is indicative of a negative result of said breath test.

26. The method according to claim 16 and wherein the presence of at least two successive measurements falling below the lower threshold, with less than a predetermined average slope between them, is indicative of a negative result of said breath test.

27. A breath test method for determining whether measurements of the change from a baseline of an isotopic ratio in a subject'"'"'s exhaled breaths, following the effective cessation of oral activity, are such that the presence of a clinically significant state in said subject is indicated, comprising the steps of:

determining a polynomial which approximates the functional plot of said measurements with time;

calculating a weighted standard deviation of said measurements from said polynomial, wherein for measurements over said baseline by more than a predetermined amount, a certain fractional part of the measurement is taken, while for measurements not over said baseline by more than said predetermined amount, the measurement is taken in its entirety; and

determining whether said weighted standard deviation exceeds a predetermined level.

28. A breath test method for determining when the measured change in isotopic ratio of a breath sample deviates sufficiently from a baseline measurement that a clinically significant result of the breath test may be concluded, wherein said threshold comprises an upper and a lower threshold band of uncertainty, and wherein the extent of this band is dependent on at least one of the parameters selected from the group consisting of the elapsed time of said breath test, the standard deviation of the physiological spread of results, the dynamics of the physiological change in isotopic ratio, the number of points measured in the breath test, the environmental conditions present during the breath test, and the noise and drift levels of the instrument executing the breath test.

29. A method for determining the reliability of a breath test measurement, as a function of at least one of the criteria selected from the group consisting of the instrument noise and drift level, the standard deviation of the physiological spread of results, the dynamics of the physiological change in isotopic ratio, and the time elapsed since ingestion of a labeled substrate.

30. The method according to claim 29 and wherein said reliability is expressed as a parameter which is taken into account in determining when a clinically significant result has been obtained in said breath test, in order to terminate said test.

31. The method according to claim 29 and wherein said reliability is expressed as a parameter which is output with the result of the breath test.

32. A method of calibrating a breath test instrument, by continuous analysis of results of breath tests of a plurality of subjects, without the need for externally supplied calibration means.

33. The method of calibrating a breath test instrument according to claim 32 and also without the need for operator involvement.

34. The method of calibrating a breath test instrument according to claim 32 and also without the need for active subject involvement.

35. The method of calibrating a breath test instrument according to claim 32, and wherein said continuous analysis comprises searching for correlation between the isotopic ratios of a gas species measured in said samples and the concentration of said gas species in said samples.

36. The method of calibrating a breath test instrument according to claim 32, and wherein said continuous analysis comprises searching for correlation between the isotopic ratios of a gas species measured in said samples and an environmental condition present at the time of said breath tests.

37. The method according to claim 36, wherein said environmental condition is the ambient temperature.

38. A method of calibrating a breath test instrument, by analyzing results obtained on breath samples of a plurality of subjects not showing change of any significance in the isotopic ratios of a specific gas species measured in said samples, for correlation between said isotopic ratios and the concentration of said gas species in said samples.

47. A method of retroactively correcting the results of a breath test from the effects of incorrect calibration, comprising the steps of:

performing a calibration procedure according to the method of claim 38 to determine the existence of correlation between measured isotopic ratios and the concentration of gas species in the breath samples;

correcting the calibration of the instrument by means of corrected parameters of the gas absorption curves to eliminate said correlation; and

recalculating the data of prior breath tests using said absorption curves with corrected parameters.

39. A method of calibrating a breath test instrument, by analyzing results obtained on a plurality of collected breath samples from one subject for correlation between the isotopic ratios of a specific gas species measured in said samples and the concentrations of said gas species in said samples.

48. A method of retroactively correcting the results of a breath test from the effects of incorrect calibration, comprising the steps of:

performing a calibration procedure according to the method of claim 39 to determine the existence of correlation between measured isotopic ratios and the concentration of gas species in the breath samples;

correcting the calibration of said instrument by means of corrected parameters of its gas absorption curves to eliminate said correlation; and

recalculating the data of prior breath tests using said absorption curves with corrected parameters.

49. The method of claim 48, and comprising the additional step of collecting at least one additional sample from said subject before correcting the calibration of said instrument.

40. A method of calibrating a breath test instrument, comprising the steps of:

(a) collecting a breath sample containing a specific gaseous species;

(b) measuring the concentration of said specific gaseous species in said sample;

(c) determining the isotopic ratio of said specific gaseous species in said sample;

(d) diluting said sample such that said concentration of said specific gaseous species changes;

(e) determining said isotopic ratio again;

(f) repeating steps (d) to (f) to obtain measurements on a number of different concentrations of said sample;

(g) looking for correlation between isotopic ratios and concentrations of said different concentrations of said sample; and

(h) adjusting the calibration of said breath test instrument to reduce any correlation found.

41. A method of correcting a change in the calibration of a gas analyzer for determining the isotopic ratio between a first isotopic species of samples of a gas and a second isotopic species of said samples of a gas, comprising the steps of:

(a) assigning a concentration C1 to each measured value of transmission T1 of said first isotope species for each sample, by assuming given values for the parameters of the absorption curve for said first isotope species;

(b) calculating the concentration, C2 of the second isotopic species for each sample measured, by assuming a predetermined ratio between the concentrations of said first isotopic species and said second isotopic species;

(c) by means of a best-fit calculation, generating new parameters of the absorption curve for said second isotope species, by using, for each sample, said generated value of C2 and a measured value of the transmission T2 of said second isotope species;

(d) generating a set of corrected transmissions T2_C of said second isotopic species, by insertion of said calculated values of C2 obtained in step (b) into said new absorption curve for said second isotope species generated in step (c);

(e) calculating the differences between said measured values of transmission T2 of said second isotope species, and said corrected transmissions T2_C obtained in step (d);

(f) calculating a set of normalized error differences Δ

T2=(T2_C−

T2)/T2 for said second isotopic species;

(g) by means of a best-fit calculation, generating from said set of normalized error differences Δ

T2, a polynomial of Δ

T2 as a function of the values of the concentration C1 of said first isotopic species; and

(h) using said polynomial to obtain iteratively corrected values of transmissions T2_C′

of said second isotopic species, in place of the initially measured values T2.

100. A method of calibrating a breath tester comprising the steps of:

performing a system check on said breath tester by the use of at least two gases having known isotopic ratio differences between them;

comparing the deviation in the differences in the isotopic ratios measured by said breath tester from those of said at least two gases; and

if said deviation exceeds a predetermined value, performing a calibration of said breath tester according to the method of claim 41.

170. A method of using a gas analyzer for determining change in the isotopic ratio of gaseous samples relative to a predetermined isotopic ratio, wherein said gas analyzer is calibrated according to the method of claim 41 using the same predetermined isotopic ratio.

171. The method of claim 170, wherein said predetermined ratio is the isotopic ratio of carbon 13 to that of carbon 12, as found in the naturally occurring mineral Pee Dee Belemnite limestone.

172. The method of claim 170, wherein said gaseous samples are collected breath samples, and said predetermined ratio is a ratio of breath components typical of a population to be measured.

42. A method of correcting a change in the calibration of a gas analyzer for determining the isotopic ratio between a first component and a second component of a gaseous sample, comprising the steps of:

measuring the concentration of said first component by means of optical transmission measurements;

calculating the concentration of said second component from said measured concentration of said first component, by assuming a predetermined ratio between said components; and

correcting transmission measurements made on said second component such that a concentration derived therefrom is essentially equal to the concentration calculated in the previous step from said measured concentration of said first component.

43. The method of claim 42, wherein said components of said gas samples are isotopic components.

44. The method of claim 43, wherein said predetermined ratio is the isotopic ratio of carbon 13 to that of carbon 12, as found in the naturally occurring mineral Pee Dee Belemnite limestone.

45. The method of claim 43, wherein said components are components of collected breath samples, and said predetermined ratio is a ratio of said components typical of a population to be measured.

46. The method of claim 42, wherein said step of correcting said transmission measurements made on said second component is performed by calculating corrected absorption curves for said second component.

50. A method of calibration of a capnographic probe, operative for measuring input breath waveforms in a breath test instrument, comprising the steps of:

(a) estimating the integrated concentration of the accumulated breaths collected according to the measured capnograph waveforms;

(b) measuring the concentration of a sample of said accumulated breaths in the gas analyzer of the breath test instrument; and

(c) correcting the calibration of said capnographic probe such that it provides the same concentration as that measured by the gas analyzer.

51. A breath test instrument which monitors changes in an isotopic ratio of a gas in exhaled breath samples of a subject virtually continuously, and determines that said test has a clinically significant outcome in accordance with the ongoing results of said test.

56. A breath test instrument according to claim 51, such that the outcome of said test is substantially independent of dynamic physiological effects occurring in said subject as a result of background conditions.

57. A breath test instrument according to claim 56, and wherein said background conditions are the result of treatment with a drug therapy.

58. A breath test instrument according to claim 56, and wherein said background conditions are the result of food intake in a period prior to the performance of the breath test.

59. A breath instrument according to claim 58, and wherein the need for a pre-test fast by the subject is obviated.

60. A breath test instrument according to claim 51, and wherein the outcome of said test on said subject undergoing treatment with a gastrointestinal drug therapy, is obtained more reliably than using corresponding breath tests which do not monitor said changes in an isotopic ratio substantially continuously.

61. A breath test instrument according to claim 51, and wherein the outcome of said test is obtained more reliably than would be obtained by corresponding breath test instruments which do not monitor said changes in an isotopic ratio substantially continuously.

62. A breath test instrument according to claim 51, and in which said outcome of said test is obtained sooner than would be obtained by corresponding breath test instruments which do not monitor said changes in an isotopic ratio substantially continuously.

63. A breath test instrument according to claim 51, and in which said ongoing results of said test enable a positive result to be determined even when said isotopic ratio does not clearly exceed a predetermined threshold level.

64. A breath test instrument according to claim 51, and in which said ongoing results of said test enable a negative result to be determined even when said isotopic ratio clearly exceeds a predetermined threshold level.

65. A breath test instrument according to claim 64, and in which said negative result is determined because said isotopic ratio exceeds said predetermined threshold level because of instrumental drift.

66. A breath test instrument according to claim 51, and in which said ongoing results of said test enable a negative result to be determined because of the detection of correlation between said isotopic ratio and instrumental drift.

52. A breath test instrument comprising a signal for indicating that a clinically significant outcome of a breath test has been determined.

53. A breath test instrument according to claim 52, and wherein said signal is a visible signal.

54. A breath test instrument according to claim 53, and wherein said signal is an audible signal.

55. A breath test instrument according to claim 54, and wherein said signal also indicates the nature of the clinically significant outcome of said breath test.

67. A method of ensuring that the correct isotopically labeled substance kit is used for a specific breath test by means of the addition of a marker element to said substance, said marker element being selected to have an immediate and short term effect on the breath test, and the provision within the breath test instrumentation of a detector for said marker element.

68. The method of claim 67 and wherein said breath test instrumentation also comprises means for enabling the instrument to perform analysis of the results of the breath test samples only after detection of said marker element.

69. A method for determining when the effects of oral activity have subsided during execution of a breath test, by monitoring change in an isotopic ratio in samples of breath collected from a subject following the ingestion of an isotopically labeled substrate, to detect the presence of a meaningful peak over a predefined minimum threshold level occurring in said isotopic ratio, within a time shorter than the time taken to detect the physiological effect of interest in the breath test.

70. The method according to claim 69, and wherein said meaningful peak subsides within a characteristic time interval from the ingestion of said isotopically labeled substrate.

71. The method according to claim 70, and wherein said characteristic time interval is 8 minutes.

72. A method, in a breath test procedure, of determining a baseline level for an isotopic ratio of a gaseous species in exhaled breath of a subject before ingestion of an isotopically labeled substrate, comprising the steps of:

performing a measurement of a first baseline point;

assessing the reliability of said measurement; and

performing a second measurement of at least one additional baseline point if the reliability of measurement of said first baseline point is determined to be inadequate.

73. The method according to claim 72, and wherein said reliability of said measurement of said first baseline point is determined to be inadequate if the standard deviation of scatter of the separate results making up said measurement exceeds a predetermined value.

74. The method according to claim 72, and wherein said reliability of said measurement of said first baseline point is determined to be inadequate if a sample with a concentration of said gaseous species within a predetermined level of the target value has not been collected.

75. A method, in a breath test procedure, of determining a baseline level for an isotopic ratio of a gaseous species in exhaled breath of a subject, before ingestion of an isotopically labeled substrate, comprising the step of measuring at least first and second baseline points.

76. The method according to claim 75, and wherein the mean of said two points is used as the baseline value, if the first two of said at least two baseline points fall within a predetermined range of each other.

77. The method according to claim 75, and wherein a third baseline point is measured if the first two of said at least two baseline points do not fall within a predetermined range of each other.

78. The method according to claim 77, and wherein if the first two of said at least two baseline points do not fall within a predetermined range of each other, the point more distant from said third baseline point is discarded.

79. The method according to claim 75, and wherein the breath test procedure is expedited by collection of said exhaled breath of a subject for determining said second baseline point before analysis of said first baseline point is completed.

80. The method according to claim 75, and wherein the breath test procedure is expedited by ingestion of said isotopically labeled substrate before the results of the analysis of said second baseline point are known.

81. A breath simulator device for checking the system functionality of a breath test instrument, which provides gas samples to simulate exhaled breaths of a subject.

82. A breath simulator device according to claim 81 and wherein said simulation of exhaled breaths of a subject, comprises at least one of the properties selected from the group consisting of flow rate, total gas species concentration, isotopic ratio of said gas species sample, and respiration rate.

83. A system checking device comprising a porous tube which allows preferential diffusion through its wall of one component of a calibrating gas.

84. A system checking device according to claim 83 and wherein said porous tube is operative to amend the isotopic ratio of a calibrating gas during passage through it.

85. A system checking device according to claim 84 and also comprising gas switching means for alternating the output of said device between calibration gas with and without an amended isotopic ratio.

86. A system checking device according to claim 85 and wherein said gas switching means is operative also for alternating the output of said device between calibration gas with and without an amended isotopic ratio, and air without any calibrating gas.

87. A system checking device according to claim 86 and wherein said gas switching means operates at a switching rate in a range similar to human respiration rate.

88. A system checking device comprising:

a calibrating gas inlet conduit supplying calibrating gas to a porous tube, said porous tube allowing preferential diffusion through its wall of one component of said calibrating gas;

a calibrating gas outlet conduit, conveying calibrating gas with an amended composition from said porous tube;

an outer chamber through which said porous tube passes, said outer chamber being continually flushed with a purging gas to remove any component of said calibrating gas which diffuses through said wall of said porous tube.

89. A system checking device according to claim 88 operative to amend the isotopic ratio of a calibrating gas during passage through it.

90. A system checking device according to claim 89 and also comprising gas switching means for alternating the output of said device between calibration gas with and without an amended isotopic ratio.

91. A system checking device according to claim 90 and wherein said gas switching means is operative also for alternating the output of said device between calibration gas with and without an amended isotopic ratio, and air without any calibrating gas.

92. A system checking device according to claim 91 and wherein said gas switching means operates at a switching rate in a range similar to a human respiration rate.

93. A breath tester incorporating a system checking device according to claim 92, and also comprising a receiver into which is inserted a container of calibrating gas, said receiver including means for enabling a calibration check procedure in said breath tester.

94. A breath tester according to claim 93, and wherein said container of calibrating gas is made of glass, and insertion of said container into said receiver actuates breakage of said glass, thereby releasing said calibrating gas.

95. A breath tester according to claim 93, and wherein said container of calibrating gas is closed by means of a pressure seated check valve, and insertion of said container into said receiver depresses said check valve, thereby releasing said calibrating gas.

96. A breath tester according to claim 93, and wherein said container of calibrating gas is closed by means of a thin metallic foil, and insertion of said container into said receiver enables a needle to penetrate said thin foil, thereby releasing said calibrating gas.

97. A breath tester according to claim 93, and wherein said container of calibrating gas is made of a hermetically sealed flexible plastic bag.

98. A breath tester incorporating a system checking procedure, operative to ensure that said breath tester is enabled only if a routine mandatory system check is performed after a predetermined number of breath tests.

99. A breath tester according to claim 98, and also operative to ensure that said breath tester is enabled only if an authorized and new container of calibration gas is used for said routine mandatory system check.

101. A system checking device for use with a gas analyzer, comprising:

a calibration checking unit; and

an enabling mechanism for enabling operation of said gas analyzer.

102. A system checking device for use with a gas analyzer according to claim 101 and wherein said enabling mechanism is operative to count the number of tests performed by said gas analyzer.

103. A system checking device for use with a gas analyzer according to claim 101 and wherein said enabling mechanism is operative to accumulate the time of operation of said gas analyzer.

104. A system checking device for use with a gas analyzer according to claim 101 and also comprising a filter for removing fluids from a gas to be analyzed.

105. A system checking device for use with a gas analyzer according to claim 101 and wherein said enabling mechanism is actuated by the use of said calibration checking unit.

106. A system checking device for use with a gas analyzer according to claim 104 and wherein said enabling mechanism for enabling operation of said gas analyzer is operated by said filter.

107. A system checking device for use with a gas analyzer according claim 101 and wherein said enabling mechanism is communicative with said gas analyzer by means of a signal selected from a group consisting of electrical, electronic, optical, mechanical, magnetic, pneumatic and gaseous signals.

108. A system checking device for use with a gas analyzer according to claim 101 and wherein said enabling mechanism is operative to ensure proper location of said calibration checking unit.

109. A system checking device for use with a gas analyzer according claim 101 and wherein said enabling mechanism comprises optical transmitter and receiver means, the optical path between which is completed by reflection from said calibration checking unit only when said calibration checking unit is properly located in said gas analyzer.

118. A system checking device for use with a gas analyzer according to claim 101 and wherein said calibration checking unit releases a calibration checking gas of known composition into said gas analyzer.

119. A system checking device for use with a gas analyzer according to claim 118 and wherein said enabling mechanism is actuated by release of said calibration checking gas.

122. A system checking device for use with a gas analyzer according to claim 101 and wherein said enabling mechanism is actuated by means of an active integrated circuit disposed on said system checking device.

125. A system checking device for use with a gas analyzer according to claim 104 and wherein said filter is a section of a sampling tube having built-in fluid filtering properties.

126. A system checking device for use with a gas analyzer according to claim 122 and also comprising a filter for removing fluids from a gas to be analyzed.

127. A system checking device for use with a gas analyzer according to claim 126 and wherein said filter comprises a drying agent disposed in proximity to at least part of an inside wall of said sampling tube.

128. A system checking device for use with a gas analyzer according to claim 104 and wherein the construction of said calibration checking unit and said filter are such as to essentially maintain the waveform of a breath of gas to be analyzed.

146. A system checking device for use with a gas analyzer according to claim 101 and wherein said enabling mechanism is operative to accumulate the time since the last system check of said gas analyzer.

110. A system checking device for use with a gas analyzer, comprising:

a calibration checking unit; and

a count actuating mechanism initiated by first use of said system checking device, operative to begin a count of the number of tests performed with said system checking device.

111. A system checking device for use with a gas analyzer according to claim 110 and also comprising a filter for removing fluids from the gas to be analyzed.

112. A system checking device for use with a gas analyzer according to claim 110 and wherein said count actuating mechanism is actuated by said calibration checking unit.

113. A system checking device for use with a gas analyzer according to claim 111 and wherein said count actuating mechanism is actuated by said filter.

114. A system checking device for use with a gas analyzer according to claim 110 and wherein said count is used to prevent use of said gas analyzer after a predetermined number of tests have been performed.

115. A system checking device for use with a gas analyzer according to claim 110 and wherein said count of the number of tests performed with said system checking device is performed within the gas analyzer.

116. A system checking device for use with a gas analyzer according to claim 110 and wherein said count of the number of tests performed with said system checking device is performed within the system checking device.

117. A system checking device for use with a gas analyzer according to claim 110 and wherein said count actuating mechanism is communicative with said gas analyzer by means of a signal selected from a group including electrical, electronic, optical, mechanical, magnetic, pneumatic and gaseous signals.

120. A system checking device for use with a gas analyzer according to claim 110 and wherein said calibration checking unit releases a calibration checking gas of known composition into said gas analyzer.

121. A system checking device for use with a gas analyzer according to claim 120 and wherein said count actuating mechanism is actuated by release of said calibration gas.

123. A system checking device for use with a gas analyzer according to claim 110 and wherein said count actuating mechanism is actuated by means of an active integrated circuit disposed on said system checking device.

124. A system checking device for use with a gas analyzer according to claim 110, and also comprising a disenabling device which prevents said count actuating mechanism from being reinitiated after first use of said system checking device.

129. A system checking device for use with a gas analyzer, comprising:

a sampling line for conveying a gas to be analyzed to said gas analyzer;

at least one enclosure housing at least one container of calibration gas;

at least one mechanism for releasing said calibration gas in said at least one container into said enclosure, said mechanism having interactive control contact with said gas analyzer; and

at least one delivery conduit connecting between said enclosure and said sampling tube for conveying said calibration gas after release into said sampling line.

130. A system checking device for use with a gas analyzer according to claim 129 and wherein said interactive control contact comprises the actuation of said mechanism by means of said gas analyzer.

131. A system checking device for use with a gas analyzer according to claim 129 and wherein said interactive control contact comprises the transmission of a signal to said gas analyzer on actuation of said mechanism.

132. A system checking device for use with a gas analyzer according to claim 129, and wherein said at least one container of calibration gas comprises two containers of calibration gas.

133. A system checking device for use with a gas analyzer according to claim 129, and wherein said at least one delivery conduit comprises two delivery conduits.

134. A calibration checking unit for use with a gas analyzer, comprising:

a calibration gas mixture comprising at least a first and a second gas; and

a delivery conduit for conveying said calibration gas mixture to said gas analyzer, said delivery conduit comprising a material which allows preferential diffusion through its wall of at least one of said at least a first and a second gas.

135. A calibration checking unit for use with a gas analyzer according to claim 134, and wherein said material is a selective membrane.

136. A calibration checking unit for use with a gas analyzer according to claim 134, and wherein said material is a porous diffusive tube.

137. A kit for system checking a gas analyzer comprising at least one calibration checking unit and a plurality of disposable sampling tubes for each of at least one calibration checking unit.

138. A kit for system checking a gas analyzer according to claim 137, and wherein at least one of said sampling tubes comprises a fluid filter.

139. A kit for system checking a gas analyzer comprising:

at least one calibration checking unit capable of interactive communication with said gas analyzer; and

a plurality of disposable sampling tubes for each of said at least one calibration checking unit.

140. A kit for system checking a gas analyzer according to claim 139, and wherein at least one of said sampling tubes comprises a fluid filter.

141. A calibration checking unit operative to generate a second calibration material from a first material input thereto.

142. A calibration checking unit according to claim 141 and wherein said first material is also a calibrating material.

143. A calibration checking unit according to claim 141 and wherein said materials are gases for use in a gas analyzer.

144. A breath bringer which changes a characteristic during use.

145. A breath bringer according to claim 144, and wherein said characteristic is a color.

147. A method of constructing an improved, electrically excited, gas discharge lamp, whose output is characteristic of spontaneous emission of at least one IR-active gas species to a ground state, comprising the steps of:

constructing a lamp envelope;

cleaning said lamp envelope; and

filling said envelope with a gas mixture comprising said at least one IR-active gas species;

the improvement being the additional step of including a catalytic material within said lamp envelope.

148. The method according to claim 147, wherein said catalytic material is operative to increase the spectral stability of said lamp by reducing changes with time in the level of self-absorption in said gas mixture.

149. The method according to claim 147 wherein said catalytic material is coated on an inside wall of said envelope.

150. The method according to claim 147, wherein said catalytic material is chosen from a group comprising gold, silver, rhodium, iridium, palladium, platinum and nickel.

154. The method according to claim 147, wherein said IR-active gas species is carbon dioxide.

151. A method of constructing an improved electrically excited gas discharge lamp, whose output is characteristic of spontaneous emission of at least one IR-active gas species to a ground state, comprising the steps of:

constructing a lamp envelope;

cleaning said lamp envelope; and

filling said envelope with a gas mixture comprising said at least one IR-active gas species;

the improvement being the additional step of including a catalytic material within said lamp envelope, such that the volume of said lamp can be decreased.

152. The method according to claim 151, wherein said lamp volume is less than approximately 6 milliliters.

155. The method according g to claim 151, wherein said IR-active gas species is carbon dioxide.

153. A method of constructing an improved electrically excited gas discharge lamp, whose output is characteristic of spontaneous emission of at least one IR-active gas species to a ground state, comprising the steps of:

constructing a lamp envelope;

cleaning said lamp envelope; and

filling said envelope with a gas mixture comprising said at least one IR-active gas species;

the improvement being the additional step of including a catalytic material within said lamp envelope, such that the IR-active gas concentration can be decreased.

156. The method according to claim 153, wherein said IR-active gas species is carbon dioxide.

157. The method according to claim 156, wherein the concentration of said carbon dioxide is less than approximately 5%.

158. An improved electrically excited gas discharge lamp, whose output is characteristic of spontaneous emission of at least one IR-active gas species to a ground state, comprising:

a lamp envelope containing a gas mixture comprising said at least one IR-active gas species; and

electrodes external to said envelope for exciting said at least one IR-active gas species;

the improvement being a catalytic material located within said lamp envelope.

159. The lamp according to claim 158, wherein said catalyst is operative to increase the spectral stability of said lamp by reducing changes with time in the level of self-absorption in said gas mixture.

160. The lamp according to claim 158, wherein said catalytic material is coated on an inside wall of said envelope.

161. The lamp according to claim 158, wherein said catalytic material is chosen from a group comprising gold, silver, rhodium, iridium, palladium, platinum and nickel.

162. The lamp according to claim 158, wherein said IR-active gas species is carbon dioxide.

163. A method of determining change in isotopic ratio in a plurality of at least a first, a second and a third gaseous sample collected at different points in time, wherein said change in isotopic ratio is determined by measuring the isotopic ratio of said second sample in relation to said first sample, and in relation to said third sample.

164. A method of reducing the effect of changes in the operating conditions of a gas analyzer on isotopic ratios measured in a series of at least three gaseous samples, by measuring the isotopic ratio of at least one sample in relation to a sample collected before and a sample collected after said at least one sample.

165. A method of determining change in the isotopic ratio between a first and a second gaseous sample, comprising the steps of:

(a) measuring said isotopic ratio of said first sample;

(b) measuring said isotopic ratio of said second sample;

(c) determining the difference between said isotopic ratios;

(d) dividing said difference by one of said ratios; and

(e) adding said change to a previous change determined between a prior first and second sample.

166. The method according to claim 165, and wherein said difference is divided by said isotopic ratio of said first sample.

167. The method according to claim 165, and wherein said difference is divided by said isotopic ratio of said second sample.

168. The method according to claim 165, and wherein said difference is divided by said isotopic ratio of said first sample when said ratio of said first sample is higher than said ratio of said second sample, and said difference is divided by said isotopic ratio of said second sample when said ratio of said second sample is higher than said ratio of said first sample.

169. A method of determining change in isotopic ratio in a plurality of at least a first, a second and a third gaseous sample collected at different points in time, wherein said change in isotopic ratio is determined by measuring the isotopic ratio of said second sample in relation to said first sample, and in relation to said third sample, each of said change in isotopic ratio being determined by the method of claim 165.

173. A method of determining change in the isotopic ratio between a first and a second gaseous sample, comprising the steps of:

(a) measuring said isotopic ratio of said first sample;

(b) measuring an isotopic ratio of a reference sample;

(c) computing a first difference between said first two isotopic ratios;

(d) measuring said isotopic ratio of said second sample;

(e) remeasuring an isotopic ratio of said reference sample;

(f) computing a second difference between said second two isotopic ratios; and

(g) subtracting one of said first and said second differences from the other.

174. A method of determining change in the isotopic ratio between a first and a second gaseous sample, comprising the steps of:

(a) measuring said isotopic ratio of said first sample;

(b) measuring a first isotopic ratio of a reference sample;

(c) computing a first difference between said isotopic ratio of said first sample and said first isotopic ratio of a reference sample;

(d) normalizing said first difference relative to said first isotopic ratio of said reference sample;

(e) measuring said isotopic ratio of said second sample;

(f) measuring a second isotopic ratio of said reference sample;

(g) computing a second difference between said isotopic ratio of said second sample and said second isotopic ratio of said reference sample;

(h) normalizing said second difference relative to said second isotopic ratio of said reference sample; and

(i) determining said change in said isotope ratio by subtracting one of said normalized differences from the other.

175. The method according to claim 174 and wherein said samples are breath samples collected from a subject.

176. The method according to claim 175 and wherein said reference sample is a baseline sample.

177. The method according to claim 175 and wherein said reference sample is obtained from a reservoir of said reference sample gas.

178. In a breath test, a method of determining change of an isotopic ratio in a plurality of breath samples of a subject, comprising the steps of:

(a) collecting a reference sample of breath;

(b) determining the isotopic ratio of a first one of said plurality of breath samples by comparison with that of said reference breath sample;

(c) determining the isotopic ratio of a second one of said plurality of breath samples by comparison with that of said reference breath sample; and

(d) computing the change in said determined isotopic ratios between said first one and said second one of said plurality of breath samples.

179. The method according to claim 178 and wherein said reference sample is a baseline sample collected before the effects of any ingested identifying substrate are observed.

180. The method of claim 178, wherein said steps of comparing said isotopic ratio of said plurality of breath samples with that of said reference breath sample is performed by measurement of said reference breath sample in its own reference chamber.

181. The method of claim 178, wherein said steps of comparing said isotopic ratio of said plurality of breath samples with that of said reference breath sample is performed by introducing said reference breath sample into a sample measurement chamber alternately between separate ones of said plurality of breath samples.

182. The method of claim 178, wherein a separate portion of said reference sample is used for comparing said isotopic ratios of each of said plurality of breath samples.

183. An apparatus for executing the method of claim 178, and comprising a reference chamber for containing said reference sample during measurement.

184. An apparatus for executing the method of claim 178, and comprising ports for introducing said reference breath sample into a sample measurement chamber alternately between separate ones of said plurality of breath samples.