Optical sensor having a selectable sampling distance for determination of analytes
First Claim
1. A method for determining the concentration of an analyte in a biological sample, said method comprising the steps of:
- (a) selecting an analyte, the concentration of which analyte is to be determined;
(b) selecting a single light introduction site from at least one light introduction site and a single light collection site from at least one light collection site on a surface of said biological sample, said single light collection site located at a distance from said single light introduction site, said distance of said single light collection site from said single light introduction site corresponding to a sampling depth in said biological sample, at which sampling depth an optical property of said biological sample is significantly affected by said analyte;
(c) introducing a beam of light into said biological sample at said single light introduction site;
(d) collecting the light re-emitted from said biological sample at said single light collection site;
(e) determining the intensity of said collected light; and
(f) determining the concentration of said analyte from said intensity of said collected light, wherein the concentration of said analyte is determined by means of a calibration relationship, said calibration relationship relating said intensity of said collected light at said distance of said single light introduction site from said single light collection site to said concentration of said analyte.
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Abstract
A method and apparatus for the measurement of trans-cutaneous diffuse reflectance at a single sampling distance for determining the concentration of an analyte in a biological sample, such as, for example, human tissue. The determination of the concentration of the analyte has been found to depend on the sampling distance and reaches an optimal result at a defined sampling distance for a given analyte and a given sample. The method involves measuring the light re-emitted from the sample at a distance from a light introduction site and correlating the intensity of the re-emitted light to the concentration of an analyte. For a given sample, the distance between the light collection site and a light introduction site (i.e., the sampling distance) corresponds to the depth from the surface into the sample at which scattering and absorption events significantly affect the intensity of re-emitted light (i.e., the sampling depth). Prior knowledge about the sample determines the optimal sampling depth for performing a measurement for a specific analyte and the corresponding sampling distance needed to reach that optimal sampling depth. Optimization of the sampling distance, as well as the correlation relationship, can be established in a calibration procedure.
302 Citations
70 Claims
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1. A method for determining the concentration of an analyte in a biological sample, said method comprising the steps of:
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(a) selecting an analyte, the concentration of which analyte is to be determined;
(b) selecting a single light introduction site from at least one light introduction site and a single light collection site from at least one light collection site on a surface of said biological sample, said single light collection site located at a distance from said single light introduction site, said distance of said single light collection site from said single light introduction site corresponding to a sampling depth in said biological sample, at which sampling depth an optical property of said biological sample is significantly affected by said analyte;
(c) introducing a beam of light into said biological sample at said single light introduction site;
(d) collecting the light re-emitted from said biological sample at said single light collection site;
(e) determining the intensity of said collected light; and
(f) determining the concentration of said analyte from said intensity of said collected light, wherein the concentration of said analyte is determined by means of a calibration relationship, said calibration relationship relating said intensity of said collected light at said distance of said single light introduction site from said single light collection site to said concentration of said analyte. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A method for determining the concentrations of a plurality of analytes in a biological sample, said method comprising the steps of:
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(a) selecting at least one analyte of a plurality of analytes, the concentration of which at least one analyte is to be determined;
(b) selecting a single light introduction site and a single light collection site from a plurality of light collection sites on a surface of said biological sample, said single light collection site located at a distance from said single light introduction site, said distance of said single light collection site from said single light introduction site corresponding to a sampling depth in said biological sample, at which sampling depth an optical property of said biological sample is significantly affected by said at least one analyte of said plurality of analytes;
(c) introducing a beam of light into said biological sample at said single light introduction site;
(d) collecting the light re-emitted from said biological sample at said single light collection site on said surface of said biological sample;
(e) determining the intensity of said collected light;
(f) determining the concentration of said at least one analyte of said plurality of analytes from said intensity of said collected light; and
(g) repeating steps (a), (b), (c), (d), (e), and (f) for at least another of said plurality of analytes, wherein the concentrations of said analytes are determined by means of calibration relationships, said calibration relationships relating said intensity of said collected light at said distances of said single light introduction site from said plurality of light collection sites to said concentrations of said analytes. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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23. A method for determining the concentrations of a plurality of analytes in a biological sample, said method comprising the steps of:
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(a) selecting at least one analyte of a plurality of analytes, the concentration of which at least one analyte is to be determined;
(b) selecting a single light introduction site from a plurality of light introduction sites and a single light collection site on a surface of said biological sample, said single light collection site located at a distance from said single light introduction site, said distance of said single light collection site from said single light introduction site corresponding to a sampling depth in said biological sample, at which sampling depth an optical property of said biological sample is significantly affected by said at least one analyte of said plurality of analytes;
(c) introducing light into said biological sample at said single light introduction site;
(d) collecting the light re-emitted from said biological sample at said single light collection site;
(e) determining the intensity of said collected light;
(f) determining the concentration of at least one of said plurality of analytes from said intensity of said collected light; and
(g) repeating steps (a), (b), (c), (d), (e), and (f) for at least another of said plurality of analytes, wherein the concentrations of said analytes are determined by means of calibration relationships, said calibration relationships relating said intensity of said collected light at said distance of said single light collection site from said plurality of light introduction site to said concentrations of said analytes. - View Dependent Claims (24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
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35. A method for generating a calibration relationship for measuring at least one analyte in a biological sample, said method comprising the steps of:
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(a) introducing a beam of light into said biological sample at a light introduction site on a surface of said biological sample;
(b) collecting the light re-emitted from said biological sample at each of a plurality of light collection sites on said surface, each of said plurality of light collection sites being at a different sampling distance from said light introduction site;
(c) determining the intensity of said light collected at each of said plurality of light collection sites;
(d) determining a correlation relationship between said intensity of said light collected at each of said plurality of light collection sites with the concentration of said at least one analyte, said concentration determined by an independent reference method;
(e) comparing said correlation relationships for said different sampling distances; and
(f) determining an optimal sampling distance for said at least one analyte for subsequent measurement of the concentration of said at least one analyte in a biological sample. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44, 45)
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46. A method for generating a calibration relationship for measuring at least one analyte in a biological sample, said method comprising the steps of:
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(a) introducing a beam of light into said biological sample at each of a plurality of light introduction sites on a surface of said biological sample;
(b) collecting the light re-emitted from said biological sample at a light collection site on said surface, each of said plurality of light introduction sites being at a different sampling distance from said light collection site;
(c) determining the intensity of said light collected for each of said plurality of light introduction sites;
(d) determining a correlation relationship between said intensity of said light collected for each of said plurality of light introduction sites with the concentration of said at least one analyte, said concentration determined by an independent reference method;
(e) comparing said correlation relationships for said different sampling distances; and
(f) determining an optimal sampling distance for said at least one analyte for subsequent measurement of the concentration of said at least one analyte in a biological sample. - View Dependent Claims (47, 48, 49, 50, 51, 52, 53, 54, 55, 56)
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57. An apparatus for the determination of the concentration of an analyte in a biological sample, said apparatus comprising:
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(a) means for introducing a beam of light into said biological sample at a single light introduction site on a surface of said biological sample;
(b) means for collecting light re-emitted from said biological sample at a single light collection site on said surface located at a predetermined sampling distance from said light introduction site, said predetermined sampling distance corresponding to a sampling depth, at which sampling depth an optical property of said biological sample is significantly affected by said analyte;
(c) means for determining the intensity of said collected light; and
(d) means for determining the concentration of said analyte from said intensity of said collect light. - View Dependent Claims (58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70)
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Specification