Method and apparatus for measuring the phase shift induced in a light signal by a sample

• US 20100006773A1
• Filed: 06/01/2009
• Published: 01/14/2010
• Est. Priority Date: 07/27/2004
• Status: Active Grant

• Current Assignee: Precisense A/S (Medtronic Plc)
• Original Assignee: Precisense A/S (Medtronic Plc)
• Inventors: Aasmul, Soren
• Granted Patent: US 7,884,338 B2
• Time in Patent Office: Days
• US Class Current: 250/459.100
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001

Abstract

A first light source emits a light signal along a measurement optical path that includes a sample and a second light source emits a light signal along a dummy measurement optical path. A measurement circuit receives the light signals and provides outputs separated in time which are indicative of the phase of the respective light signals. A phase shift is induced in light in the measurement optical path by the sample. A reference circuit receives a signal indicative of the phase of the light signals emitted by the first and second light sources. Circuitry compares the phases of light output from the two circuits to provide output indicative of a first measured phase difference during operation of the first light source. Correction is applied to this measurement by taking a similar phase difference measurement during operation of the second light source and comparing the two phase differences.

Claims

1-60. -60. (canceled)

61. Apparatus for measuring a phase shift induced in a light signal by a sample, the apparatus comprising:

a first light source for emitting a light signal along a measurement optical path, wherein the measurement optical path includes a sample location;

a second light source for emitting a light signal along a dummy measurement optical path, the first and second light sources being arranged for alternate operation;

a measurement electronic circuit for receiving the light signals from the measurement and dummy measurement optical paths, the measurement electronic circuit being arranged to provide outputs separated in time which are respectively indicative of the phase of the light signals received from each of the measurement and dummy measurement optical paths, wherein in use a phase shift is induced in light in the measurement optical path by a sample in said sample location such that the phase of light of the first light source received from the measurement optical path is different to the phase of light emitted from the first light source;

a reference electronic circuit for receiving a signal indicative of the phase of the light signals emitted by the first and second light sources;

circuitry to compare the phase of light indicated by the output of the measurement electronic circuit responsive to the first light source with the phase of light indicated by the reference electronic circuit to provide an output indicative of a first measured phase difference and to compare the phase of light indicated by the output of the measurement electronic circuit responsive to the second light source with the phase of light indicated by the reference electronic circuit to provide an output indicative of a second measured phase difference, and circuitry to apply a correction to the first measured phase difference on the basis of the second measured phase difference to correct for errors in said first measured phase difference due to phase changes induced by said measurement and reference electronic circuits so as to obtain an improved measurement of the shift in phase induced in the light of the first light source by the sample.

62. Apparatus as claimed in claim 61, wherein the first light source further emits a light signal along a reference optical path, and the second light source further emits a light signal along a dummy reference optical path, wherein the reference electronic circuit further comprises means for receiving the light signals from the reference and dummy reference optical paths, the reference electronic circuit being arranged to provide outputs separated in time which are respectively indicative of the phase of the light signals received from each of the reference and dummy reference optical paths.

63. Apparatus as claimed in claim 61, wherein the measurement optical path comprises a beam splitter receiving light from said first light source and reflecting said light toward said sample location and receiving fluorescence emission light in use emitted from said sample location and transmitting said fluorescence emission light to said measurement electronic circuit.

64. Apparatus as claimed in claim 61, wherein said measurement optical path comprises an excitation filter arranged to select a wave length of light suitable for exciting a first fluorescent sample at said sample location and an emission filter suitable for selecting a wave length of fluorescent light emitted from said sample location.

65. Apparatus as claimed in claim 61 wherein an oscillator is coupled to each of the first and second light sources to produce light signals of oscillating intensity.

66. Apparatus as claimed in claim 63, wherein the dummy measurement path comprises said beam splitter, the beam splitter being arranged to receive light from the second light source, reflect said light toward said sample location, receive said light reflected from said sample location and transmit the light to said measurement electronic circuit.

67. Apparatus as claimed in claim 66, wherein the dummy measurement optical path further comprises the said emission filter for selecting a wavelength of light comparable to the wavelength of fluorescent light emitted from the sample location.

68. Apparatus as claimed in claim 63, wherein light from the second light source is not received by the beam splitter and is guided directly to the measurement electronic circuit.

69. Apparatus as claimed in claim 61, wherein the light in the dummy measurement path does not include a wave length of light suitable for exciting the first fluorescent sample.

70. Apparatus as claimed in claim 63, wherein the dummy measurement path comprises said beam splitter, and the beam splitter is arranged to receive light from said second light source, reflect said light towards said sample location, receive fluorescence emission light in use emitted from said sample location and to transmit said fluorescence light to said measurement circuit.

71. Apparatus as claimed in claim 61, wherein means are provided for guiding light from the first and second light sources along the reference and dummy reference optical paths respectively to an opto-electric converter of the reference circuit.

72. Apparatus as claimed in claim 61, wherein light modulated at two or more different frequencies are alternately generated and output from each of the first and second light sources consecutively to enable further calculations.

73. Apparatus as claimed in claim 61 for use in a glucose measuring system, wherein the sample has fluorescence characteristics which can be modulated by the concentration of glucose present in the sample.

74. A method of measuring a phase shift induced in a light signal by a sample, comprising the steps of:

emitting a first light signal along a measurement optical path, wherein the measurement optical path includes a sample location;

emitting a second light signal along a dummy-measurement optical path, the first and second light signals being emitted alternately;

receiving light signals from the measurement and dummy-measurement optical paths in a measurement electronic circuit;

providing outputs separated in time from the measurement electronic circuit, wherein the outputs are respectively indicative of the phase of the light signals received from each measurement and dummy-measurement optical path;

receiving a signal indicative of the phase of the first and second light signals in a reference electronic circuit;

comparing the phase of light indicated by the output of the measurement electronic circuit and responsive to the first light signal with the phase of light indicated by the reference electronic circuit;

providing an output indicative of the first measured phase difference;

comparing the phase of light indicated by the output of the measurement electronic circuit in response to the second light signal with the phase of light indicated by the reference electronic circuit;

providing an output indicative of a second measured phase difference;

applying a correction to the first measured phase difference on the basis of the second measured phase difference to correct errors in said first measured phase difference due to phase changes induced by said measurement and reference electronic circuit so as to obtain an improved measurement of the shifting phase induced in the light of the first light source by the sample.

75. A method as claimed in claim 74 further comprising:

additionally emitting the first light signal along a reference optical path and the second light signal along a dummy-reference optical path;

receiving the light signals from the reference and dummy-reference optical paths in the reference electronic circuit;

outputting from the reference electronic circuit signals separated in time which are respectively indicative of the phase of each of the light signals received from the reference and dummy-reference optical paths.

76. A method as claimed in claims 74, further comprising:

selecting a wavelength of light for the first light signal suitable for exciting a first fluorescent sample at said sample location; and

selecting a wavelength of fluorescent light emitted from said sample location.

77. A method as claimed in claim 74, further comprising producing first and second light signals of oscillating intensity.

78. A method as claimed in claim 74, further comprising:

receiving the first light signal emitted along the dummy measurement path in a beam splitter;

reflecting said light toward said sample location; and

transmitting the light to said measurement circuit.

79. A method as claimed in claim 74, further comprising:

converting the light signal received in the measurement electronic circuit into an electrical signal corresponding to an intensity of the light signal; and

outputting the electrical signal.

80. A method as claimed in claim 74, further comprising guiding the first and second light signals from the first and second light sources respectively along the reference and dummy reference paths to an opto-electric converter of the reference circuit.