Method and device for the quantitative determination of dissolved substances in single- or multicomponent systems of laser light scattering

Claim 2

A process for the quantitative determination of the concentration of dissolved low molecular weight and high molecular weight substances, and of blood particles or blood cells in multi-component systems, in which the individual components sufficiently differ in the linear dimensions of their molecules, in structure, and/or in composition and/or in molecular mass, by (a) light scattering at the sample and analysis of the scattering curve configuration and determination of at least one scattering angle range per component to be detected, in which there is maximum dependence of the intensity of the scattered radiation on the concentration of the respective component, (b) correction of the measured intensity of the respective scattered radiation with the measured intensity of the central beam, and (c) attribution of the corrected measured value to the concentration of the component to be determined.

Claim 3

Method according to claim 1, characterized in that the intensity of the scattered radiation is measured while the scattering angle is continuously varied.

Claim 4

Method according to claim 1, characterized in that the intensity of the scattered radiation is measured at a single predetermined scattering angle or in a single predetermined scattering angle range.

Claim 5

Method according to claim 1, characterized in that the intensity of the scattered radiation is measured at a plurality of discrete predetermined scattering angles, or in a plurality of scattering angle ranges, and optionally, upon appropriate evaluation, several components of a multi-component solution are determined simultaneously.

Claim 6

Method according to one of claims 1 to 4, characterized in that the measured signal is corrected upon varying actual sample thickness, e.g. for blood flow correction, and the corrective quantity is derived from the measured intensity of the central beam.

Claim 7

Method according to one of claims 1 to 5, characterized in that the correction of the measured signal is effected digitally such that the mode thereof is determined by a mathematical function and its quantity is predetermined by the input of constants.

Claim 8

Method according to one of claims 1 to 5, characterized in that the correction of the measured signal is effected analogously by suitable amplification control and by comparison with an adjustable rated value, e.g. the voltage level of a potentiometer.

Claim 9

Method according to one of claims 1 to 7, characterized in that a light source with linearly, elliptically, or circularly polarized radiation is employed.

Claim 10

Method according to one of claims 1 to 8, characterized in that signal processing is performed analogously in steps (b) and (c).

Claim 11

Method according to one of claims 1 to 8, characterized in that the measured value of the scattered radiation after correction is corrected by means of the intensity of the central beam according to one or more relative intensities.

Claim 12

Method according to one of claims 1 to 8, characterized in that a two-signal or multi-signal technique is adopted, and the measured intensity of the scattered radiation is corrected by forming the difference to obtain a reference value according to one or more relative intensities and/or products of intensities.

Claim 13

Method according to one of claims 1 to 11, characterized in that the measured values are averaged prior to or after correction.

Claim 14

Method according to one of claims 1 to 12, characterized in that for measurement of the intensity of the scattered radiation and of the central beam only a single light detector is used, and the angle of the light source relative to the sample is varied by movement of the light source and/or by movable deflecting mirrors.

Claim 15

Method according to one of claims 1 to 13, characterized in that between sample and light detector(s) filters are interposed which improve the measuring accuracy and suppress parasitic scattered radiation.

Claim 16

Apparatus for carrying out the method according to one of claims 1 to 14, comprising

Claim 17

- a light source, - a sample member, - one or more light detectors detecting the intensity of the central beam and of the scattered radiation in at least one predetermined angular range, - an electronic signal processing means for correction of the measured signals, - a power supply, and - a signal display means or signal output means, characterized by - a substantially U-shaped support (T) with a joint (G) provided in its bottom region and with a spring urging the two side portions of the support towards each other under spring pressure, and with the side portions spaced apart a distance to allow the insertion of a human earlobe into the space between the two side portions of the support (T) to be held therebetween, - a laser diode (D) provided as light source at or in a side portion of the support (T) and optionally arranged in a cooling block (K), - a deflecting mirror (U) mounted above the laser -diode (D) and deflecting the light emitted by the laser diode (D) by about 80o to substantially horizontal direction, and - an optical receiving unit (E) provided opposite the deflecting mirror (U) at the other side portion of the support and comprising at least one light detector detecting the intensity of the central beam and of the scattered radiation of the light from the laser diode (D) beamed or scattered, respectively, through the earlobe introduced into the support (T) in at least one predetermined angular range and providing corresponding electric signals, - said electronic signal processing means, signal display means, and/or signal output means and the power supply being integrated with the support (T) or provided independently thereof.

Claim 18

- a light source, - a sample member, - one or more light detectors detecting the intensity of the central beam and of the scattered radiation in at least one predetermined angular range, - an electronic signal processing means for correction of the measured signals, - a power supply, and - a signal display means or signal output means, characterized by - a substantially U-shaped support (T) with a joint (G) provided in its bottom region and with a spring urging the two side portions of the support towards each other under spring pressure, and with the side portions spaced apart a distance to allow the insertion of a human earlobe into the space between the two side portions of the support (T) to be held therebetween, - a laser diode (D) provided as light source at or in a side portion of the support (T) and optionally arranged in a cooling block (K), - a deflecting mirror (U) mounted above the laser -diode (D) and deflecting the light emitted by the laser diode (D) by about 80o to substantially horizontal direction, and - an optical receiving unit (E) provided opposite the deflecting mirror (U) at the other side portion of the support and comprising at least one light detector detecting the intensity of the central beam and of the scattered radiation of the light from the laser diode (D) beamed or scattered, respectively, through the earlobe introduced into the support (T) in at least one predetermined angular range and providing corresponding electric signals, - said electronic signal processing means, signal display means, and/or signal output means and the power supply being integrated with the support (T) or provided independently thereof.

Claim 19

Apparatus according to claim 15, characterized by an optical receiving unit (E) which is so designed that it separately covers two angular ranges by sectoring.

Claim 20

Apparatus according to claims 15 or 16, characterized in that the optical receiving unit (E) is designed as an optical pipe.

Claim 21

Apparatus according to one of claims 15 to 17, characterized by an optical receiving unit (E) comprising a housing (5p) in the bottom face of which a light detector (2p) is centrically disposed and whose inner surface tapers conically outwardly, when seen from the light detector (2p), an annular glass member (3p) made of glass or another light-transmissive material and provided concentrically in the cone surface on the open side of the housing (5p) so that the inner surface of said member tapers conically outwardly, when seen from the light detector (2p), a sleeve (4p) which is radiation impermeable or radiation-impermeably coated and arranged concentrically in the glass member (3p) and closed at its outwardly facing end, except for a central opening, and a light detector (1 p) disposed concentrically in the sleeve (4p) in the optical axis of the system, the diameter (D1) of the central opening in the sleeve (4p), the diameter (D2) of the externally disposed bottom face of the sleeve (4p), and the diameter (D3) of the externally disposed bottom face of the glass member (3p) and the cone half-angle (a) of the sleeve (4p) and the cone half-angle (β) of the housing (5p), or of the inner cone of the glass member (3p), respectively, being so selected that the scattered radiation arriving in the underlying scattering angle range is substantially completely detected by the light detector (2p).

Claim 22

Apparatus according to claim 18, characterized in that the inner surface of the housing (5p) or the outer surface of the glass member (3p), respectively, and/or the outer surface of the sleeve (4p) or the inner surface of the glass member (3p), respectively, have a parabolically curved cross section.

Claim 23

Apparatus according to claims 15 or 16, characterized by a flat optical receiving unit composed of four superposed layers (1 to 4), the lowermost layer (1) being photosensitive, the overlying second layer (2) being radiation-impermeable and having a central opening of the diameter (D1) disposed in the optical axis, the overlying third layer (3) being photosensitive and having a central concentric opening of the diameter (D2), and the overlying fourth layer (4) having a concentric central opening of the diameter (D3), the diameters (D1, D2, D3, respectively) being so selected that the layer (1) substantially completely detects the central beam, and the layer (3) substantially completely detects the scattered radiation arriving in the scattering angle range underlying the measurement.

Claim 24

Apparatus according to claims 15 or 16, characterized by a flat optical receiving unit composed of three superposed layers (5 to 7), with the topmost layer (5) being light-impermeable and having an annular opening of the diameters (D2 and D3) and a central opening of the diameter (D1), and below the topmost layer (5) a photosensitive layer (6) with a central concentric opening of a diameter between (D1 and D2), and therebelow a photosensitive layer (7), the diameters (D1 and D2, D3, respectively) being so selected that the layer (7) detects the central beam and the layer (6) substantially completely detects scattered radiation arriving in the scattering angle range underlying the measurement.

Claim 25

Apparatus according to one of claims 15 to 21, characterized by

Claim 26

- a servo amplifier (9) for the light source (10), - one or more differential amplifiers (16) delivering from the measured signals of the light detectors (12) signals corresponding to the relative intensity of the associated scattered light which are converted to corresponding digital signals in an A/D converter (20), - A/D converters (22) converting the measured signals from the light detectors (12), one of which detects the intensity of the central beam and the others detect the intensity of the scattered radiation emanating from the sample (11), after amplification in signal amplifiers (13, 14, 15), to corresponding digital signals, and - a measured value processing unit (17) which, on the basis of predetermined functions or programs, produces at the digital signals from the light detectors (12), or from the differential amplifier(s) (16), output signals for a display means (18) or for an output means (19) with D/A converter (23) before the input, and further produces an output quantity which, after conversion to an analog signal in a D/A converter (21), is delivered to the servo amplifier (9).

Claim 27

- a servo amplifier (9) for the light source (10), - one or more differential amplifiers (16) delivering from the measured signals of the light detectors (12) signals corresponding to the relative intensity of the associated scattered light which are converted to corresponding digital signals in an A/D converter (20), - A/D converters (22) converting the measured signals from the light detectors (12), one of which detects the intensity of the central beam and the others detect the intensity of the scattered radiation emanating from the sample (11), after amplification in signal amplifiers (13, 14, 15), to corresponding digital signals, and - a measured value processing unit (17) which, on the basis of predetermined functions or programs, produces at the digital signals from the light detectors (12), or from the differential amplifier(s) (16), output signals for a display means (18) or for an output means (19) with D/A converter (23) before the input, and further produces an output quantity which, after conversion to an analog signal in a D/A converter (21), is delivered to the servo amplifier (9).

Claim 28

Apparatus according to one of claims 15 to 21, characterized by - a servo amplifier (9) for the light source (10), - a differential amplifier with integrator (22') integrating the difference signal of the measured signals (a, b) of two light detectors (12) one of which detects the intensity of the central beam and the other one the intensity of the scattered radiation emanating from the sample (11), - two serially connected controllable amplifiers (23', 24) further amplifying the output signal from the differential amplifier with integrator (22'), - a ratio former (25) forming the ratio (a/b) of the two measured signals (a, b) and controlling with a corresponding output signal the amplifier (23'), - an amplifier (13) amplifying the measured signal (a), and - a differential amplifier (16) which compares the output signal from the amplifier (13) with a predetermined reference voltage, and whose output signal controls the amplifier (24).

Claim 29

Apparatus according to one of claims 15 to 23, characterized by a laser diode as light source.

Claim 30

Apparatus according to one of claims 15 to 24, characterized by phototransistors as light detectors for measuring the intensity of the central beam and of the scattered radiation.

Claim 31

Apparatus according to one of claims 15 to 25, characterized by a microcomputer or microprocessor as or in the signal processing unit, respectively.

Claim 32

Apparatus according to one of claims 15 to 26, characterized by a recorder, a plotter, or a miniature printer, optionally combined with a pocket calculator, as output means (19).

Claim 33

Apparatus according to one of claims 15 to 27, characterized by a means giving off an acoustical, optical and/or electrical signal when a predetermined upper and/or lower limit of the measured value is reached.

Claim 34

Apparatus according to one of claims 15 to 28, characterized in that it is microminiaturized.

Claim 35

30 Apparatus according to one of claims 15 to 29, characterized in that it is designed for controlling an infusion device.

Claim 36

Apparatus according to claim 30, characterized in that it is designed for controlling an insulin infusion device.

Claim 37

Apparatus according to one of claims 15 to 31, characterized by a temperature measuring sensor for measuring the skin temperature, and a means for correcuing the measured signal according to a predetermined correction function on the basis of the detected skin temperature.