Method and aparatus for determining an analyte in a biological sample
First Claim
1. A method for the analytical determination of a concentration of an analyte in a biological sample, said method comprising the steps of:
- performing at least two detection measurements, each detection measurement comprising the step of irradiating light at an irradiation site as primary light into the biological sample through a boundary surface thereof, said light being propagated along a light path within the biological sample, and detecting light as the light emerges from the biological sample as secondary light through a detection site at the boundary surface, said irradiation site and said detection site being separated by a predetermined measuring distance;
wherein said at least two detection measurements are carried out with at least two different measurement light paths between the irradiation site and the detection site, said at least two different measurement light paths being provided by a plurality of detection sites with a plurality of detection means, each of said plurality of detection sites having different measuring distances from the irradiation site, each of said at least two detection measurements is a frequency-domain spectroscopic measurement being performed at at least two different wavelengths of light, and wherein each frequency-domain spectroscopic measurement includes a comparison of a phase shift of the secondary light with the primary light as a first measurement variable and an intensity of the secondary light as a second measurement variable, said method further comprising a step ofdetermining an analyte concentration in the biological sample based upon the first and second measurement variables.
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Abstract
A method and apparatus for analytical determination of a concentration of an analyte in a biological sample include a series of hardware elements and method steps which perform at least two detection measurements, with each detection measurement including the step of irradiating light at an irradiation site as primary light into the biological sample through a boundary surface. The light is propagated along a light path, and light is detected as it emerges from the biological sample as secondary light through a detection site. The irradiation site and detection site are separated by a measuring distance. At least two detection measurements are performed with at least two different measurement light paths between the irradiation site and the detection site. Each of the detection measurements is a frequency-domain spectroscopic measurement which is performed at at least two different wavelengths of light, and includes a comparison of a phase shift of the secondary light with the primary light as a first measurement variable, and an intensity of the secondary light as a second measurement variable. The method also includes the steps of determining the analyte concentration based upon the first and second measurement variables.
176 Citations
51 Claims
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1. A method for the analytical determination of a concentration of an analyte in a biological sample, said method comprising the steps of:
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performing at least two detection measurements, each detection measurement comprising the step of irradiating light at an irradiation site as primary light into the biological sample through a boundary surface thereof, said light being propagated along a light path within the biological sample, and detecting light as the light emerges from the biological sample as secondary light through a detection site at the boundary surface, said irradiation site and said detection site being separated by a predetermined measuring distance; wherein said at least two detection measurements are carried out with at least two different measurement light paths between the irradiation site and the detection site, said at least two different measurement light paths being provided by a plurality of detection sites with a plurality of detection means, each of said plurality of detection sites having different measuring distances from the irradiation site, each of said at least two detection measurements is a frequency-domain spectroscopic measurement being performed at at least two different wavelengths of light, and wherein each frequency-domain spectroscopic measurement includes a comparison of a phase shift of the secondary light with the primary light as a first measurement variable and an intensity of the secondary light as a second measurement variable, said method further comprising a step of determining an analyte concentration in the biological sample based upon the first and second measurement variables. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. A method for the analytical determination of a concentration of an analyte in a biological sample, said method comprising the steps of:
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performing at least two detection measurements, each detection measurement comprising the step of irradiating light at an irradiation site as primary light into the biological sample through a boundary surface thereof, said light being propagated along a light path within the biological sample, and detecting light as the light emerges from the biological sample as secondary light through a detection site at the boundary surface, said irradiation site and said detection site being separated by a predetermined measuring distance; wherein said at least two detection measurements are carried out with at least two different measurement light paths between the irradiation site and the detection site, the at least two different measurement light paths in the biological sample being directed to a selected volume of the sample where an analyte concentration is desired to be determined, each of said at least two detection measurements is a frequency-domain spectroscopic measurement being performed at at least two different wavelengths of light, wherein each frequency-domain spectroscopic measurement includes a comparison of a phase shift of the secondary light with the primary light as a first measurement variable and an intensity of the secondary light as a second measurement variable, said method further comprising a step of determining the analyte concentration in the biological sample based upon the first and second measurement variables. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)
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29. An apparatus for analytical determination of a concentration of an analyte in a biological sample, said apparatus comprising:
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a measuring head for engaging a surface of the biological sample; irradiation means attached to said measuring head for irradiating primary light into the biological sample at an irradiation site on the surface of the biological sample, said irradiation means including a light transmitter; detection means for detecting secondary light emerging from the biological sample at a detection site through the surface of the biological sample, said detection means including a light receiver, said detection means being connected to said measuring head; first frequency generator means connected to said irradiation means for modulating the primary light with a first high-frequency modulation; phase measuring means connected to said detection means for determining a phase shift measurement variable of the secondary light with respect to the primary light; intensity measuring means connected to said detection means for determining an intensity measurement variable of the secondary light; and evaluation means connected to said phase measuring means and said intensity measuring means for determining an analyte concentration of the biological sample from an output of the phase measuring means and the intensity measuring means, wherein the output of the phase measuring means and the output of the intensity measuring means are generated without movement of the irradiation means and the detection means, and are based upon two different measurement light paths between the irradiation site and the detection site;
said apparatus further comprisingdriver means connected to said first frequency generator means for driving the light transmitter; and an electromagnetically insulating housing for electromagnetically insulating the driver means and the light transmitter. - View Dependent Claims (30, 31, 32, 33, 34, 35)
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36. An apparatus for analytical determination of a concentration of an analyte in a biological sample, said apparatus comprising:
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a measuring head for engaging a surface of the biological sample; irradiation means attached to said measuring head for irradiating primary light into the biological sample at an irradiation site on the surface of the biological sample, said irradiation means including a light transmitter; detection means for detecting secondary light emerging from the biological sample at a detection site through the surface of the biological sample, said detection means including a light receiver, said detection means being connected to said measuring head; first frequency generator means connected to said irradiation means for modulating the primary light with a first high-frequency modulation; phase measuring means connected to said detection means for determining a phase shift measurement variable of the secondary light with respect to the primary light; intensity measuring means connected to said detection means for determining an intensity measurement variable of the secondary light; and evaluation means connected to said phase measuring means and said intensity measuring means for determining analyte concentration of the biological sample from an output of the phase measuring means and the intensity measuring means, wherein the output of the phase measuring means and the output of the intensity measuring means are generated without movement of the irradiation means and the detection means, and are based upon two different measurement light paths between the irradiation site and the detection site;
said apparatus further comprisinga plurality of said detection means, each detection means of said plurality of detection means simultaneously detecting light emerging from the biological sample at different detection sites. - View Dependent Claims (37, 38, 39, 40, 41, 42, 43, 44)
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45. An apparatus for analytical determination of a concentration of an analyte in a biological sample, said apparatus comprising:
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a measuring head for engaging a surface of the biological sample; irradiation means attached to said measuring head for irradiating primary light into the biological sample at an irradiation site on the surface of the biological sample, said irradiation means including a light transmitter; detection means for detecting secondary light emerging from the biological sample at a detection site through the surface of the biological sample, said detection means including a light receiver, said detection means being connected to said measuring head; first frequency generator means connected to said irradiation means for modulating the primary light with a first high-frequency modulation; phase measuring means connected to said detection means for determining a phase shift measurement variable of the secondary light with respect to the primary light; intensity measuring means connected to said detection means for determining an intensity measurement variable of the secondary light; and evaluation means connected to said phase measuring means and said intensity measuring means for determining an analyte concentration of the biological sample from an output of the phase measuring means and the intensity measuring means, wherein the output of the phase measuring means and the output of the intensity measuring means are generated without movement of the irradiation means and the detection means, and are based upon two different measurement light paths between the irradiation site and the detection site;
said apparatus further comprisinghigh-frequency amplifying means connected to said detection means, said high-frequency amplifying means for amplifying an output of the light receiver, wherein a connection distance between the light receiver and the high-frequency amplifier means is minimized.
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46. An apparatus for analytical determination of a concentration of an analyte in a biological sample, said apparatus comprising:
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a measuring head for engaging a surface of the biological sample; irradiation means attached to said measuring head for irradiating primary light into the biological sample at an irradiation site on the surface of the biological sample, said irradiation means including a light transmitter; detection means for detecting secondary light emerging from the biological sample at a detection site through the surface of the biological sample, said detection means including a light receiver, said detection means being connected to said measuring head; first frequency generator means connected to said irradiation means for modulating the primary light with a first high-frequency modulation; phase measuring means connected to said detection means for determining a phase shift measurement variable of the secondary light with respect to the primary light; intensity measuring means connected to said detection means for determining an intensity measurement variable of the secondary light; and evaluation means connected to said phase measuring means and said intensity measuring means for determining an analyte concentration of the biological sample from an output of the phase measuring means and the intensity measuring means, wherein the output of the phase measuring means and the output of the intensity measuring means are generated without movement of the irradiation means and the detection means, and are based upon two different measurement light paths between the irradiation site and the detection site;
said apparatus further comprising signal mixer means for mixing a plurality of signals produced from the phase measuring means and the intensity measuring means, said signal mixer means being connected to an output of the light receiver, wherein a length of a signal path between the light receiver and the signal mixer means is minimized. - View Dependent Claims (47, 48, 49)
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50. An apparatus for analytical determination of a concentration of an analyte in a biological sample, said apparatus comprising;
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a measuring head for engaging a surface of the biological sample; irradiation means attached to said measuring head for irradiating primary light into the biological sample at an irradiation site on the surface of the biological sample, said irradiation means including a light transmitter; detection means for detecting secondary light emerging from the biological sample at a detection site through the surface of the biological sample, said detection means including a light receiver, said detection means being connected to said measuring head; first frequency generator means connected to said irradiation means for modulating the primary light with a first high-frequency modulation; phase measuring means connected to said detection means for determining a phase shift measurement variable of the secondary light with respect to the primary light; intensity measuring means connected to said detection means for determining an intensity measurement variable of the secondary light; and evaluation means connected to said phase measuring means and said intensity measuring means for determining an analyte concentration of the biological sample from an output of the phase measuring means and the intensity measuring means, wherein the output of the phase measuring means and the output of the intensity measuring means are generated without movement of the irradiation means and the detection means, and are based upon two different measurement light paths between the irradiation site and the detection site;
said apparatus further comprisingoptical reference means connected to said detection means for providing a reference light path which essentially corresponds to one of the two different measurement light paths with respect to light transit time and light intensity attenuation, and optical switching means for optically switching the light between one of the measurement light paths and the reference light path.
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51. An apparatus for analytical determination of a concentration of an analyte in a biological sample, said apparatus comprising:
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a measuring head for engaging a surface of the biological sample; irradiation means attached to said measuring head for irradiating primary light into the biological sample at an irradiation site on the surface of the biological sample, said irradiation means Including a light transmitter; detection means for detecting secondary light emerging from the biological sample at a detection site through the surface of the biological sample, said detection means including a light receiver, said detection means being connected to said measuring head; first frequency generator means connected to said irradiation means for modulating the primary light with a first high-frequency modulation; phase measuring means connected to said detection means for determining a phase shift measurement variable of the secondary light with respect to the primary light; intensity measuring means connected to said detection means for determining an intensity measurement variable of the secondary light; and evaluation means connected to said phase measuring means and said intensity measuring means for determining an analyte concentration of the biological sample from an output of the phase measuring means and the intensity measuring means, wherein the output of the phase measuring means and the output of the intensity measuring means are generated without movement of the irradiation means and the detection means, and are based upon two different measurement light paths between the irradiation site and the detection site;
said apparatus further comprisingsecond frequency generator means connected to said first frequency generator means, said first and second frequency generator means being configured to oscillate with a constant difference frequency therebetween, said difference frequency being determined by a difference frequency generator means, and wherein a frequency of the second frequency generator means is controlled based upon the difference frequency to follow frequency fluctuations of the first frequency generator means.
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Specification