WO2007009541A1 - Medical test device and method for the optical determination of an analyte comprising means for compensating the ambient light background - Google Patents
Medical test device and method for the optical determination of an analyte comprising means for compensating the ambient light background Download PDFInfo
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- WO2007009541A1 WO2007009541A1 PCT/EP2006/005821 EP2006005821W WO2007009541A1 WO 2007009541 A1 WO2007009541 A1 WO 2007009541A1 EP 2006005821 W EP2006005821 W EP 2006005821W WO 2007009541 A1 WO2007009541 A1 WO 2007009541A1
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- lightdetector
- signal
- light
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- sample
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- 238000010339 medical test Methods 0.000 title claims abstract description 17
- 239000012491 analyte Substances 0.000 title claims abstract description 16
- 230000003287 optical effect Effects 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 title claims description 7
- 238000005259 measurement Methods 0.000 claims abstract description 59
- 238000012360 testing method Methods 0.000 claims abstract description 11
- 210000004369 blood Anatomy 0.000 claims abstract description 10
- 239000008280 blood Substances 0.000 claims abstract description 10
- 238000001514 detection method Methods 0.000 claims abstract description 10
- 239000012530 fluid Substances 0.000 claims abstract description 10
- 230000003993 interaction Effects 0.000 claims abstract description 7
- 230000001678 irradiating effect Effects 0.000 claims abstract description 5
- 239000013307 optical fiber Substances 0.000 claims description 19
- 239000000835 fiber Substances 0.000 claims description 18
- 239000004065 semiconductor Substances 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 7
- 239000000758 substrate Substances 0.000 claims description 2
- 230000031700 light absorption Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 13
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000013060 biological fluid Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000001795 light effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/02—Details
- G01J1/04—Optical or mechanical part supplementary adjustable parts
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/02—Details
- G01J1/04—Optical or mechanical part supplementary adjustable parts
- G01J1/0407—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings
- G01J1/0425—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings using optical fibers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/10—Photometry, e.g. photographic exposure meter by comparison with reference light or electric value provisionally void
- G01J1/16—Photometry, e.g. photographic exposure meter by comparison with reference light or electric value provisionally void using electric radiation detectors
- G01J1/1626—Arrangements with two photodetectors, the signals of which are compared
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/42—Photometry, e.g. photographic exposure meter using electric radiation detectors
- G01J1/4204—Photometry, e.g. photographic exposure meter using electric radiation detectors with determination of ambient light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/42—Photometry, e.g. photographic exposure meter using electric radiation detectors
- G01J1/4228—Photometry, e.g. photographic exposure meter using electric radiation detectors arrangements with two or more detectors, e.g. for sensitivity compensation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/42—Photometry, e.g. photographic exposure meter using electric radiation detectors
- G01J1/44—Electric circuits
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/02—Details
- G01J1/0214—Constructional arrangements for removing stray light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J1/00—Photometry, e.g. photographic exposure meter
- G01J1/42—Photometry, e.g. photographic exposure meter using electric radiation detectors
- G01J1/44—Electric circuits
- G01J2001/444—Compensating; Calibrating, e.g. dark current, temperature drift, noise reduction or baseline correction; Adjusting
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
- G01N21/274—Calibration, base line adjustment, drift correction
Definitions
- the invention relates to a medical test device and a method for the optical determination of a medically important analyte in an aqueous fluid sample, particularily in blood.
- a body fluid like blood or urine is analyzed with a hand-held test device utilizing test strips.
- the test strip has a reaction area impregnated with reagents, that react with an analyte of the fluid and change color as a result.
- the change in color can be quantitatively evaluated by photometric analysis.
- a common application is the measurement of blood glucose levels by diabetics.
- photometric signals have to be detected and evaluated with very high precision.
- measurement signals are usually very weak compared to noise and unwanted signals.
- the measurement signal has to be amplified by a factor of at least 1.000 in order to be separated from noise and unwanted signals.
- Chemical and biochemical components in aqueous fluids can also be quantified by the analysis of fluorescence light.
- a wavelength shift between fluorescence light and excitation light makes it easier to separate fluorescence light from excitation light, for example by use of suitable filters.
- fluorescence signals are significantly weaker than photometric signals compounding the need for detection and evaluation with very high precision.
- ambient light includes light from external sources like the sun or light bulbs as well as stray light from an internal light source that reaches the detector without interacting with the sample.
- a test device that addresses these and related problems is disclosed by US 4,553,848.
- the known device has a measurement photodiode for detection of secondary light resulting from interaction of primary light with the sample and a reference photodiode for detection of ambient light.
- a measurement and integration circuit alternately evaluates signals from the measurement photodiode and from the reference photodiode . The signals are integrated and then digitalized. The influence of ambient light on the measurement is compensated numerically by a microprocessor which calculates a quotient of a digital value derived from integrated signals provided by the measurement photodiode and a reference value derived from integrated signals provided by the reference photodiode.
- the light source of the device is activated and deactivated at timed intervals. Signals obtained from the photodiodes are evaluated in the same way during the light phase and the dark phase. By subtracting results obtained during the dark phase from those obtained during the light phase noise and unwanted signals can be significantly reduced.
- the object of the present invention is therefore to provide a test device with improved suppression of and/or compensation for unwanted signal contributions such as ambient light.
- a medical test device for the optical determination of a medically important analyte in an aqueous fluid sample, particularily in blood
- said test device comprising: A light source for irradiating a sample with primary light, a signal lightdetector which provides an analogue measurement signal characterizing the intensity of detected light, the signal lightdetector being arranged for detection of secondary light resulting from interaction of primary light with the sample, a base lightdetector which provides an analogue base signal characterizing the intensity of detected light, the base lightdetector being arranged for detection of ambient light, which may contain primary light, analyzing means for analyzing the signals created by the signal lightdetector and the base lightdetector in order to determine the presence and/or concentration of the analyte in the sample, characterized in that in order to compensate for the part of the measurement signal caused by ambient light, which is detected by the signal lightdetector in addition to secondary light, the signal lightdetector and the base lightdetector
- a method for the optical determination of a medically important analyte in a aqueous fluid sample, particularily in blood, with a medical test device comprising the following steps: irradiating the sample with primary light, guiding secondary light resulting from interaction of primary light with the sample to a signal lightdetector which creates an analogous measurement signal characterizing the intensity of detected light, detecting ambient light, which may contain primary light, with a base lightdetector creating an analogue base signal characterizing the intensity of ambient light, analyzing the measurement signal and the base signal in order to determine the presence and/or concentration of the analyte in the sample, characterized in that the measurement signal and the base signal are subtracted from each other resulting in a compensated analogue signal, which is then analyzed to determine the presence and/or concentration of the analyte in the sample.
- the present invention solves the problem that the signal lightdetector of a test device inevitably detects ambient light as well as secondary light resulting from interaction with the sample. Therefore, the measurement signal provided by the detector always contains a contribution due to ambient light. This inevitable contribution must be compensated to achieve the necessary precision for medical applications. Rather than compensating for the effect of ambient light by calculations based on complex mathematical algorithms the present invention provides a simple, precise and efficient way to compensate for ambient light before the measurement signal is digitalized and analyzed by the analyzing means.
- the signal lightdetector and the base lightdetector each produce an analogue signal, which is usually an electrical current but might also be a voltage, in response to detected light.
- the measurement signal created by the signal light detector contains a useful part caused by secondary light from the sample and an unwanted part caused by ambient light.
- the base signal is caused entirely by ambient light. Superimposing and thereby subtracting these signals from each other results in an analogue signal which contains in principle only the part of the measurement signal which was caused by secondary light from the sample.
- Fig. 1 illustrates an example of a working principle of a medical test device
- Fig. 2 shows an example of the circuitry of a medical test device according to the invention
- Fig. 3 shows another example of the circuitry of a medical test device according to the invention
- Fig. 4 shows another example of the circuitry of a medical test device according to the invention
- Fig. 5 shows an example of an optical fiber of a medical test device according to the invention
- Fig. 6 shows another example of the circuitry of a medical test device according to the invention.
- Fig. 1 illustrates an example of a working principle of a medical test device.
- An aqueous fluid sample to be analyzed is placed in a reaction area 1 at an end of a measurement channel 2 of a multi channel optical fiber 3.
- the sample is irradiated with primary light 4 emitted by a light emitting diode 5 used as a light source.
- the primary light 4 interacts with the sample in the reaction area 1 resulting in secondary light 6 which is transmitted through the measurement channel 2 of the fiber 3 to a signal lightdetector 10 arranged at the other end of the measurement channel 2 of the fiber 3.
- the multichannel fiber 3 further comprises a reference channel 11 for guiding ambient light 9 from a reference area 12 in the vicinity of the reaction area 1 to a base lightdetector 13.
- the reference channel 11 is separated from the measurement channel 2 by a partition layer 19.
- the signal light detector 10 also receives ambient light 9 which has to be compensated for.
- the reference area 12 is also covered with sample.
- the reaction area 1 is preferably part of a test strip which is placed at the end of the measurement channel 2 for an analysis.
- the test strip has a reference area close to the reaction area 1, as indicated in Fig. 1 by the reference numeral 12.
- the measurement channel 2 and the reference channel 11 of the optical fiber 3 can also be provided as separate optical fibers.
- the secondary light 6 is either light reflected by the sample or more preferably fluorescence light.
- the signal lightdetector 10 it is also possible to measure transmitted light as secondary with the signal lightdetector 10 and guide the primary light 4 to the reaction area 1 and the reference area 12 by means of a different optical fiber.
- the signal lightdetector 10 provides an analogue measurement signal characterizing the intensity of detected light consisting of secondary light 6 and ambient light 9.
- the base lightdetector 13 provides an analogue base signal characterizing the intensity of detected light and is arranged for detection of ambient light 9. For a precise measurement the part of the measurement signal caused by ambient light 9 must be compensated for.
- Fig. 2 shows an example of the circuitry to achieve such a compensation.
- diodes particularily PIN-diodes, are used as signal lightdetector 10 and base lightdetector 13.
- Each lightdetector 10, 13 provides an analogue signal, i.e. an electric current, approximately proportional to the intensity of detected light.
- the lightdetectors 10, 13 are connected with opposite polarity to a common line 14, which leads to the analyzing means 15. Therefore, the electric current created as measurement signal by the signal lightdetector 10 and the electric current created as base signal by the base lightdetector 13 flow in opposite directions along the common line 14.
- the measurement signal and the base signal are superimposed and subtracted from each other resulting in a compensated analogue signal, which is compensated for effects of ambient light 9 and provided to the analyzing means 15.
- the compensated analogue signal consists essentially of the part of the measurement current created in response to detected secondary light 6.
- the other part of the measurement current created in response to ambient light 9 and the reference current cancel each other.
- the described compensation for the effects of ambient light works best, if the two lightdetectors 10, 13 receive precisely the same amount of ambient light.
- This can be achieved by appropriate arrangement of the base lightdetector 13 and the signal lightdetector 9.
- the lightdetector 10, 13 can be embedded in a reference optical fiber 11 and a measurement optical fiber 2, respectively, which have the same transmittance values.
- the characteristic curves, i.e. the strength of the current created in response to a given intensity of light should be as identical as possible for the signal lightdetector 10 and the base lightdetector 13.
- the signal lightdetector 10 and the base lightdetector 13 are preferably semiconductor devices as these can be manufactured easily within narrow tolerances.
- the signal lightdetector 10 and the base lightdetector 13 are arranged on a joint semiconductor substrate, for example as PIN-diodes.
- Other semiconductor devices like phototransistors or photoresistors can also be used as lightdetectors 10, 13.
- Best suited for the invention are semiconductor devices which have a depletion layer, in which electrons are excited from a valence band into a conduction band by 1ight absorption .
- the compensated signal resulting from superimposing and subtracting the measurement signal and the base signal is fed to a current/voltage converter 16 which creates a voltage that is proportional to the strength of the electrical current in the common line 14 and therefore proportional to the intensity of detected secondary light, if the characteristic curve of the signal lightdetector is perfectly linear.
- the intensity of ambient light 9 has to be known.
- Non-linearities of the characteristic curve are usually due to saturation effects, i.e. with increasing intensity of detected light the additional current created in response to a given increment in the intensity of detected light decreases. If the intensity of ambient light and the characteristic curve of the lightdetector are known, any non-linearity of the characteristic curve can be compensated for by the analyzing means 15.
- the intensity of ambient light 9 can be measured by a third lightdetector 17 as shown in fig. 2.
- the electric current created by the third lightdetector 17 is provided to a current voltage converter 18 so that the resulting voltage is characteristic for the intensity of ambient light 9.
- This voltage is provided to the analyzing means 15, preferably a microprocessor which compensates effects of any non-linearity of the characteristic curve of the signal lightdetector 10 by numerical calculations.
- Fig. 3 shows an example of different circuitry, which also provides ambient light compensation.
- the signal lightdetector 10 and the base lightdetector 13 are connected to the common line 14 with opposite polarity so that the measurement current created by the signal lightdetector 10 as the measurement signal and the reference current created by the base lightdetector 13 as the base signal are superimposed and subtracted from each other resulting in an analogue signal provided to the analyzing means i5.
- the circuitry shown in fig. 3 includes a switch 20 which can be used to disconnect the signal lightdetector 10 from the common line 14 such that the base iightdetector 13 provides an analogue signal corresponding to the intensity of the ambient light 9 to the analyzing means 15.
- the analyzing means can be provided with information about the intensity of the ambient light 9 necessary to correct for any non-linearity in the characteristic curve of the signal lightdetector 10.
- the intensity of the ambient light 9 is measured both before and after the intensity of secondary light is measured. By averaging over the ambient light intensity measured before and after the intensity of secondary light effects of any fluctuations of the intensity of ambient light can be kept to a minimum.
- the intensity of ambient light 9 is much bigger than the intensity of fluorescent light (secondary light 6) . Therefore, the electric current provided over the common line 14 to the current voltage converter 16 changes significantly when the switch 20 is opened or closed. To prevent saturation of the current voltage converter 16 its gain should be adapted which can be done by switch 21.
- Fig. 4 shows another example of a circuitry for a medical test device according to the invention.
- the signal lightdetector comprises a PIN-diode 10 and a current/voltage converter 16 connected thereto. Therefore the signal lightdetector 10, 16 provides an analogue measurement signal in the form of a voltage which is proportional to the current created by the PIN-diode 10 in response to detected light.
- the base lightdetector comprises a PIN-diode 13 and a current voltage converter 22. Hence the base lightdetector 13, 22 provides an analogue base signal in the form of a reference voltage .
- the signal lightdetector 10, 16 and the base lightdetector 13, 22 are connected to the inputs of a differential amplifier 23 and the output of the differential amplifier 23 is connected to the common line 14 leading to the analyzing means 15.
- the differential amplifier 23 subtracts the reference voltage from the measurement voltage and amplifies the result. In this way a compensated analogue signal is created in the form of the output voltage of the differential amplifier 23.
- the output voltage is proportional to the intensity of secondary light 9, if the characteristic curve of the signal lightdetector 10 is perfectly linear. Any non- linearity can be compensated for by use of a third lightdetector as described with reference to fig. 2.
- Fig. 5 illustrates an example of a measurement optical fiber 2 of a medical test device according to the invention.
- Fig. 5 also shows the arrangement of the signal lightdetector 10 and the light source 5 with respect to the measurement fiber 2.
- primary light 4 is emitted by the light emitting diode 5 used as a light source.
- the primary light 4 interacts with a sample placed in reaction area 1 at the end of the optical fiber 2 resulting in secondary light 6.
- Secondary light 6 is transmitted together with ambient light 9 through the measurement fiber 2 to the signal light detector 10. Effects of primary light 4 on the signal lightdetector 10 can be minimized if primary light 4 is provided to the measurement fiber 2 by a branch 2a of the measurement fiber 2.
- primary light 4 enters the optical fiber 2 under an angle of 20° to 25° .
- a reference optical fiber can be arranged parallel to the signal optical fiber 2 as depicted in fig. 1.
- reaction area 1 on which the sample is applied can then be divided into several smaller areas, which are each analyzed in turn using a signal fiber 2 as shown in fig. 5. If results for these areas differ by more than a critical value, it can be concluded that the reaction area 1 is only partially covered with sample. In this case no precise measurement is possible.
- the analyzing means 15 will alert a user of the device to this fact with a suitable signal, for example a warning light or an acoustic signal.
- each signal fiber 2 is associated with a reference fiber 11.
- Fig. 6 shows an example of the circuitry for such a bundle of signal fibers 2 and reference fibers 11.
- Each signal fiber 2 guides light to a signal lightdetector 10 and each reference fiber 11 guides light to a base lightdetector 13. If different light sources 5 are used to irradiate different parts of the reaction area 1 it is possible to detect with increased reliability whether the reaction area 1 is properly covered by a sample .
- the output of the lock- in amplifiers can be compared. If the output is significantly different then it is highly likely that one of the signal lightdetectors 10 received significantly less secondary light than the other. This means that the corresponding part of the reaction area 1 was not or only partially covered with sample. Thus, a user can be alerted to the fact that the sample was not probably applied.
- the number of signal lightdetectors 10 and the number of base lightdetectors 13 need not necessarily be the same.
- all base lightdetectors 13 together receive the same amount of ambient light 9 as all signal light detectors 10 together.
- a single measurement optical fiber 2 leading to a single signal lightdetector can be used together with two reference optical fibers 11 each leading to a base lightdetector 13, if the cross-section of the measurement fiber 2 has the same area as the cross-sections of the two base lightdetectors 13 together.
- the analyzing means 15 to which the common line 14 is connected preferably comprises a microprocessor programmed according to the state of the art. Details can be found in US 4,553,848 and US 5,463,467. Especially, it is advantages to turn the light source on and off with a rather high frequency and use lock- in amplifiers for amplification which can be part of the analyzing means.
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- Spectroscopy & Molecular Physics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Sustainable Development (AREA)
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Abstract
The invention refers to a Medical test device for the optical determination of a medically important analyte in an aqueous fluid sample, particularly in blood, said test device comprising: a light source (5) for irradiating a sample with primary light (4), a signal lightdetector (10) which provides an analogue measurement signal characterizing the intensity of detected light and which is arranged for detection of secondary light (6) resulting from interaction of primary light (4) with the sample, a base lightdetector (13) which provides an analogue base signal characterizing the intensity of detected light and which is arranged for detection of ambient light (9) , which may contain primary light (4) , analyzing means (15) for analyzing the signals created by the signal lightdetector (10) and the base lightdetector (13) in order to determine the presence and/or concentration of the analyte in the sample. In order to compensate for the part of the measurement signal caused by ambient light (9) , which is detected by the signal lightdetector (10) in addition to secondary light (6) , the signal lightdetector (10) and the base lightdetector (13) are connected to a common line (14) , which leads to the analyzing means (15) , in such a way that the analogue signals created by the lightdetectors (10,13) are subtracted from each other resulting in a compensated analogue signal provided to the analyzing means (15).
Description
MEDICAL TEST DEVICE AND METHOD FOR THE OPTICAL DETERMINATION OF AN ANALYTE COMPRISING MEANS FOR COMPENSATING THE AMBIENT LIGHT BACKGROUND
The invention relates to a medical test device and a method for the optical determination of a medically important analyte in an aqueous fluid sample, particularily in blood.
The quantification of chemical and biochemical components in colored aqueous fluids, in particular colored biological fluids such as whole blood or urine and biological fluid derivatives such as blood serum and blood plasma, is of ever increasing importance for medical applications like diagnosis and treatment of diseases. Commonly, a body fluid like blood or urine is analyzed with a hand-held test device utilizing test strips. The test strip has a reaction area impregnated with reagents, that react with an analyte of the fluid and change color as a result. The change in color can be quantitatively evaluated by photometric analysis. A common application is the measurement of blood glucose levels by diabetics.
For such applications photometric signals have to be detected and evaluated with very high precision. However, measurement signals are usually very weak compared to noise and unwanted signals. Typically, the measurement signal has to be amplified by a factor of at least 1.000 in order to be separated from noise and unwanted signals.
Chemical and biochemical components in aqueous fluids can also be quantified by the analysis of fluorescence light. A wavelength shift between fluorescence light and excitation light makes it easier to separate fluorescence light from excitation light, for example by use of suitable filters. However, fluorescence signals are significantly weaker than photometric signals compounding the need for detection and evaluation with very high precision.
Problems encountered in the electronics of detecting very weak signals include amplifier drift, offset voltages from various components, high and low frequency noise, leakage and residual currents of various types. These problems of the measurement and evaluation electronics are compounded by the influence of ambient light on the measurement itself. In this context the term ambient light includes light from external sources like the sun or light bulbs as well as stray light from an internal light source that reaches the detector without interacting with the sample.
A test device that addresses these and related problems is disclosed by US 4,553,848. The known device has a measurement photodiode for detection of secondary light resulting from interaction of primary light with the sample and a reference photodiode for detection of ambient light. A measurement and integration circuit
alternately evaluates signals from the measurement photodiode and from the reference photodiode . The signals are integrated and then digitalized. The influence of ambient light on the measurement is compensated numerically by a microprocessor which calculates a quotient of a digital value derived from integrated signals provided by the measurement photodiode and a reference value derived from integrated signals provided by the reference photodiode. The light source of the device is activated and deactivated at timed intervals. Signals obtained from the photodiodes are evaluated in the same way during the light phase and the dark phase. By subtracting results obtained during the dark phase from those obtained during the light phase noise and unwanted signals can be significantly reduced.
However, as sample volumes are more and more reduced in order to minimize pain and inconvenience of blood glucose measurements the signal to noise ratio becomes increasingly unfavorable to the point where hand-held devices known in the art no longer yield results with the desired precision. The object of the present invention is therefore to provide a test device with improved suppression of and/or compensation for unwanted signal contributions such as ambient light.
This object is achieved by a medical test device for the optical determination of a medically important analyte in an aqueous fluid sample, particularily in blood, said test device comprising: A light source for irradiating a sample with primary light, a signal lightdetector which provides an analogue measurement signal characterizing the intensity of detected light, the signal lightdetector being arranged for detection of secondary light resulting from interaction of primary light with the sample, a base
lightdetector which provides an analogue base signal characterizing the intensity of detected light, the base lightdetector being arranged for detection of ambient light, which may contain primary light, analyzing means for analyzing the signals created by the signal lightdetector and the base lightdetector in order to determine the presence and/or concentration of the analyte in the sample, characterized in that in order to compensate for the part of the measurement signal caused by ambient light, which is detected by the signal lightdetector in addition to secondary light, the signal lightdetector and the base lightdetector are connected to a common line, which leads to the analyzing means, in such a way that the analogue signals created by the lightdetectors are subtracted from each other resulting in a compensated analogue signal provided to the analyzing means.
This object is also achieved by a method for the optical determination of a medically important analyte in a aqueous fluid sample, particularily in blood, with a medical test device, the method comprising the following steps: irradiating the sample with primary light, guiding secondary light resulting from interaction of primary light with the sample to a signal lightdetector which creates an analogous measurement signal characterizing the intensity of detected light, detecting ambient light, which may contain primary light, with a base lightdetector creating an analogue base signal characterizing the intensity of ambient light, analyzing the measurement signal and the base signal in order to determine the presence and/or concentration of the analyte in the sample, characterized in that the measurement signal and the base signal are subtracted from each other resulting in a compensated analogue
signal, which is then analyzed to determine the presence and/or concentration of the analyte in the sample.
The present invention solves the problem that the signal lightdetector of a test device inevitably detects ambient light as well as secondary light resulting from interaction with the sample. Therefore, the measurement signal provided by the detector always contains a contribution due to ambient light. This inevitable contribution must be compensated to achieve the necessary precision for medical applications. Rather than compensating for the effect of ambient light by calculations based on complex mathematical algorithms the present invention provides a simple, precise and efficient way to compensate for ambient light before the measurement signal is digitalized and analyzed by the analyzing means.
The signal lightdetector and the base lightdetector each produce an analogue signal, which is usually an electrical current but might also be a voltage, in response to detected light. The measurement signal created by the signal light detector contains a useful part caused by secondary light from the sample and an unwanted part caused by ambient light. The base signal is caused entirely by ambient light. Superimposing and thereby subtracting these signals from each other results in an analogue signal which contains in principle only the part of the measurement signal which was caused by secondary light from the sample.
Thus the invention offers a way to compensate for ambient light that is both simple and very precise.
Further details and advantages of the invention are illustrated in the following on the basis of exemplary embodiments making reference to the enclosed figures. Identical and corresponding parts are identified by identical reference numbers. The features illustrated therein can be used individually or in combination in order to create preferred further embodiments of the invention.
The following is depicted in the figures:
Fig. 1 illustrates an example of a working principle of a medical test device;
Fig. 2 shows an example of the circuitry of a medical test device according to the invention; Fig. 3 shows another example of the circuitry of a medical test device according to the invention;
Fig. 4 shows another example of the circuitry of a medical test device according to the invention;
Fig. 5 shows an example of an optical fiber of a medical test device according to the invention;
Fig. 6 shows another example of the circuitry of a medical test device according to the invention.
Fig. 1 illustrates an example of a working principle of a medical test device. An aqueous fluid sample to be analyzed is placed in a reaction area 1 at an end of a measurement channel 2 of a multi channel optical fiber 3. The sample is irradiated with primary light 4 emitted by a light emitting diode 5 used as a light source. The primary light 4 interacts with the sample in the reaction area 1 resulting in secondary light 6 which is transmitted through the measurement channel 2 of the fiber 3 to a signal lightdetector 10 arranged at the
other end of the measurement channel 2 of the fiber 3. The multichannel fiber 3 further comprises a reference channel 11 for guiding ambient light 9 from a reference area 12 in the vicinity of the reaction area 1 to a base lightdetector 13. To minimize cross-talk the reference channel 11 is separated from the measurement channel 2 by a partition layer 19. Inevitably, the signal light detector 10 also receives ambient light 9 which has to be compensated for. Preferably, the reference area 12 is also covered with sample.
The reaction area 1 is preferably part of a test strip which is placed at the end of the measurement channel 2 for an analysis. Preferably, the test strip has a reference area close to the reaction area 1, as indicated in Fig. 1 by the reference numeral 12. The measurement channel 2 and the reference channel 11 of the optical fiber 3 can also be provided as separate optical fibers.
In the example shown the secondary light 6 is either light reflected by the sample or more preferably fluorescence light. Of course, it is also possible to measure transmitted light as secondary with the signal lightdetector 10 and guide the primary light 4 to the reaction area 1 and the reference area 12 by means of a different optical fiber.
The signal lightdetector 10 provides an analogue measurement signal characterizing the intensity of detected light consisting of secondary light 6 and ambient light 9. The base lightdetector 13 provides an analogue base signal characterizing the intensity of detected light and is arranged for detection of ambient light 9. For a precise measurement the part of the
measurement signal caused by ambient light 9 must be compensated for.
Fig. 2 shows an example of the circuitry to achieve such a compensation. In the example shown diodes, particularily PIN-diodes, are used as signal lightdetector 10 and base lightdetector 13. Each lightdetector 10, 13 provides an analogue signal, i.e. an electric current, approximately proportional to the intensity of detected light. The lightdetectors 10, 13 are connected with opposite polarity to a common line 14, which leads to the analyzing means 15. Therefore, the electric current created as measurement signal by the signal lightdetector 10 and the electric current created as base signal by the base lightdetector 13 flow in opposite directions along the common line 14. Hence, the measurement signal and the base signal are superimposed and subtracted from each other resulting in a compensated analogue signal, which is compensated for effects of ambient light 9 and provided to the analyzing means 15.
The compensated analogue signal consists essentially of the part of the measurement current created in response to detected secondary light 6. The other part of the measurement current created in response to ambient light 9 and the reference current cancel each other.
Evidently, the described compensation for the effects of ambient light works best, if the two lightdetectors 10, 13 receive precisely the same amount of ambient light. This can be achieved by appropriate arrangement of the base lightdetector 13 and the signal lightdetector 9. For example the lightdetector 10, 13 can be embedded in a reference optical fiber 11 and a measurement optical fiber 2, respectively, which have the same transmittance
values. Further, the characteristic curves, i.e. the strength of the current created in response to a given intensity of light, should be as identical as possible for the signal lightdetector 10 and the base lightdetector 13.
For this reason the signal lightdetector 10 and the base lightdetector 13 are preferably semiconductor devices as these can be manufactured easily within narrow tolerances. Preferably, the signal lightdetector 10 and the base lightdetector 13 are arranged on a joint semiconductor substrate, for example as PIN-diodes. Other semiconductor devices like phototransistors or photoresistors can also be used as lightdetectors 10, 13. Best suited for the invention are semiconductor devices which have a depletion layer, in which electrons are excited from a valence band into a conduction band by 1ight absorption .
The compensated signal resulting from superimposing and subtracting the measurement signal and the base signal is fed to a current/voltage converter 16 which creates a voltage that is proportional to the strength of the electrical current in the common line 14 and therefore proportional to the intensity of detected secondary light, if the characteristic curve of the signal lightdetector is perfectly linear.
To correct for any non-linearities of the characteristic curve of the signal iightdetector 9, the intensity of ambient light 9 has to be known. Non-linearities of the characteristic curve are usually due to saturation effects, i.e. with increasing intensity of detected light the additional current created in response to a given increment in the intensity of detected light decreases.
If the intensity of ambient light and the characteristic curve of the lightdetector are known, any non-linearity of the characteristic curve can be compensated for by the analyzing means 15.
The intensity of ambient light 9 can be measured by a third lightdetector 17 as shown in fig. 2. The electric current created by the third lightdetector 17 is provided to a current voltage converter 18 so that the resulting voltage is characteristic for the intensity of ambient light 9. This voltage is provided to the analyzing means 15, preferably a microprocessor which compensates effects of any non-linearity of the characteristic curve of the signal lightdetector 10 by numerical calculations.
Fig. 3 shows an example of different circuitry, which also provides ambient light compensation. As in the example discussed with reference to fig. 2, the signal lightdetector 10 and the base lightdetector 13 are connected to the common line 14 with opposite polarity so that the measurement current created by the signal lightdetector 10 as the measurement signal and the reference current created by the base lightdetector 13 as the base signal are superimposed and subtracted from each other resulting in an analogue signal provided to the analyzing means i5.
The circuitry shown in fig. 3 includes a switch 20 which can be used to disconnect the signal lightdetector 10 from the common line 14 such that the base iightdetector 13 provides an analogue signal corresponding to the intensity of the ambient light 9 to the analyzing means 15. Thus the analyzing means can be provided with information about the intensity of the ambient light 9 necessary to correct for any non-linearity in the
characteristic curve of the signal lightdetector 10. Preferably, the intensity of the ambient light 9 is measured both before and after the intensity of secondary light is measured. By averaging over the ambient light intensity measured before and after the intensity of secondary light effects of any fluctuations of the intensity of ambient light can be kept to a minimum.
Usually, the intensity of ambient light 9 is much bigger than the intensity of fluorescent light (secondary light 6) . Therefore, the electric current provided over the common line 14 to the current voltage converter 16 changes significantly when the switch 20 is opened or closed. To prevent saturation of the current voltage converter 16 its gain should be adapted which can be done by switch 21.
Fig. 4 shows another example of a circuitry for a medical test device according to the invention. In this example the signal lightdetector comprises a PIN-diode 10 and a current/voltage converter 16 connected thereto. Therefore the signal lightdetector 10, 16 provides an analogue measurement signal in the form of a voltage which is proportional to the current created by the PIN-diode 10 in response to detected light. In the same fashion the base lightdetector comprises a PIN-diode 13 and a current voltage converter 22. Hence the base lightdetector 13, 22 provides an analogue base signal in the form of a reference voltage .
The signal lightdetector 10, 16 and the base lightdetector 13, 22 are connected to the inputs of a differential amplifier 23 and the output of the differential amplifier 23 is connected to the common line 14 leading to the analyzing means 15. The differential
amplifier 23 subtracts the reference voltage from the measurement voltage and amplifies the result. In this way a compensated analogue signal is created in the form of the output voltage of the differential amplifier 23. The output voltage is proportional to the intensity of secondary light 9, if the characteristic curve of the signal lightdetector 10 is perfectly linear. Any non- linearity can be compensated for by use of a third lightdetector as described with reference to fig. 2.
Fig. 5 illustrates an example of a measurement optical fiber 2 of a medical test device according to the invention. Fig. 5 also shows the arrangement of the signal lightdetector 10 and the light source 5 with respect to the measurement fiber 2. As explained with respect to fig. 1 primary light 4 is emitted by the light emitting diode 5 used as a light source. The primary light 4 interacts with a sample placed in reaction area 1 at the end of the optical fiber 2 resulting in secondary light 6. Secondary light 6 is transmitted together with ambient light 9 through the measurement fiber 2 to the signal light detector 10. Effects of primary light 4 on the signal lightdetector 10 can be minimized if primary light 4 is provided to the measurement fiber 2 by a branch 2a of the measurement fiber 2. Preferably, primary light 4 enters the optical fiber 2 under an angle of 20° to 25° .
Of course, a reference optical fiber can be arranged parallel to the signal optical fiber 2 as depicted in fig. 1.
Preferably, several signal fibers 2, each with its own light source 5, are employed. The reaction area 1 on which the sample is applied can then be divided into
several smaller areas, which are each analyzed in turn using a signal fiber 2 as shown in fig. 5. If results for these areas differ by more than a critical value, it can be concluded that the reaction area 1 is only partially covered with sample. In this case no precise measurement is possible. The analyzing means 15 will alert a user of the device to this fact with a suitable signal, for example a warning light or an acoustic signal.
Preferably, each signal fiber 2 is associated with a reference fiber 11. Fig. 6 shows an example of the circuitry for such a bundle of signal fibers 2 and reference fibers 11. Each signal fiber 2 guides light to a signal lightdetector 10 and each reference fiber 11 guides light to a base lightdetector 13. If different light sources 5 are used to irradiate different parts of the reaction area 1 it is possible to detect with increased reliability whether the reaction area 1 is properly covered by a sample .
If, for example, two light sources 5, which are connected to different signal fibers 2 and hence associated with different signal lightdetectors 10, are turned on and of with different frequencies or inverted phase and the common line 14 connected to lock-in amplifiers for those frequencies, the output of the lock- in amplifiers can be compared. If the output is significantly different then it is highly likely that one of the signal lightdetectors 10 received significantly less secondary light than the other. This means that the corresponding part of the reaction area 1 was not or only partially covered with sample. Thus, a user can be alerted to the fact that the sample was not probably applied.
The number of signal lightdetectors 10 and the number of base lightdetectors 13 need not necessarily be the same. It is sufficient if all base lightdetectors 13 together receive the same amount of ambient light 9 as all signal light detectors 10 together. For example, a single measurement optical fiber 2 leading to a single signal lightdetector can be used together with two reference optical fibers 11 each leading to a base lightdetector 13, if the cross-section of the measurement fiber 2 has the same area as the cross-sections of the two base lightdetectors 13 together.
The analyzing means 15 to which the common line 14 is connected preferably comprises a microprocessor programmed according to the state of the art. Details can be found in US 4,553,848 and US 5,463,467. Especially, it is advantages to turn the light source on and off with a rather high frequency and use lock- in amplifiers for amplification which can be part of the analyzing means.
Claims
1. Medical test device for the optical determination of a medically important analyte in an aqueous fluid sample, particularily in blood, said test device comprising: a light source (5) for irradiating a sample with primary light (4), a signal lightdetector (10) , which provides an analogue measurement signal characterizing the intensity of detected light, the signal lightdetector (10) being arranged for detection of secondary light (6) resulting from interaction of primary light (4) with the sample, a base lightdetector (13) which provides an analogue base signal characterizing the intensity of detected light, the base lightdetector (13) being arranged for detection of ambient light (9) , which may contain primary light (4) , analyzing means (15) for analyzing the signals created by the signal lightdetector (10) and the base lightdetector (13) in order to determine the presence and/or concentration of the analyte in the sample, characterized in that in order to compensate for the part of the measurement signal caused by ambient light (9) , which is detected by the signal lightdetector (10) in addition to secondary light (6) , the signal lightdetector (10) and the base lightdetector (13) are connected to a common line (14), which leads to the analyzing means (15) , in such a way that the analogue signals created by the lightdetectors (10,13) are subtracted from each other resulting in a compensated analogue signal provided to the analyzing means (15) .
2. Device according to claim 1, characterized in that both the signal lightdetector (10) and the base lightdetector (13) each comprise a semiconductor device which creates an analogue signal in response to detected light.
3. Device according to claim 2, characterized in that the semiconductor device of the signal lightdetector
(10) and the semiconductor device of the base lightdetector (13) are arranged on a joint semiconductor substrate.
4. Device according to claim 2 or 3, characterized in that the signal lightdetector (10) and the base lightdetector (13) each have a depletion layer, in which electrons are excited from a valence band into a conduction band by light absorption.
5. Device according to claim 4, characterized in that the signal lightdetector (10) and the base lightdetector (13) each comprise a diode, preferably a PIN-diode.
6. Device according to any one of the preceding claims, characterized in that the signal lightdetector (10) is arranged at an end of a measurement optical fiber (2) arranged for guiding the secondary light (6) from the sample to the signal lightdetector (10) .
7. Device according to claim 6, characterized in that the base lightdetector (13) is arranged at an end of a reference optical fiber (11) arranged for guiding ambient light (9) from a vicinity (12) of the entrance of the measurement optical fiber to the base lightdetector (13) .
8. Device according to claim 7, characterized in that the measurement optical fiber (2) and the reference optical fiber (11) are provided as separate channels of a multichannel fiber (3) .
9. Device according to any one of the preceding claims, characterized in that the analyzing means (15) comprises storage means, in which a characteristic curve of the signal lightdetector (10) is stored, the characteristic curve being used by the analyzing means (15) to compensate for effects of the intensity of the ambient light (9) on the part of the measurement signal created in response to detected secondary light (6) .
10. Device according to claim 9, characterized in that the intensity of the ambient light (9) is measured by a third lightdetector (17) connected to the analyzing means (15) .
11. Device according to claim 9, characterized in that it includes a switch (20) which can be used to disconnect the signal lightdetector (10) from the common line (14) such that the base lightdetector (13) provides an analogue signal corresponding to the intensity of the ambient light (9) to the analyzing means (15) .
12. Device according to any one of the preceding claims, characterized in that the measurement signal and the base signal are electrical currents.
13. Device according to any one of the preceding claims, characterized in that the signal lightdetector (10) and the base lightdetector (13) are connected to the common line (14) with opposite polarity.
14. Device according to any one of the preceding claims, characterized in that the signal lightdetector (10) and the base lightdetector (13) are connected to the inputs of a differential amplifier (23) and the output of the differential amplifier (23) being connected to the common line (14) .
15. Device according to any one of the preceding claims, characterized in that the secondary light (6) is fluorescence light.
16. Device according to any of the preceding claims, characterized in that it is a hand-held device.
17. Method for the optical determination of a medically important analyte in a aqueous fluid sample, particularily in blood, with a medical test device, the method comprising the following steps: irradiating the sample with primary light (4), guiding secondary light (6) resulting from interaction of primary light (4) with the sample to a signal lightdetector (10) which creates an analogous measurement signal characterizing the intensity of detected light, detecting ambient light (9) , which may contain primary light (4) , with a base lightdetector (13) creating an analogue base signal characterizing the intensity of ambient light (9) , analyzing the measurement signal and the base signal in order to determine the presence and/or concentration of the analyte in the sample, characterized in that the measurement signal and the base signal are subtracted from each other resulting in a compensated analogue signal, which is then analyzed to determine the presence and/or concentration of the analyte in the sample.
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DE200510033327 DE102005033327A1 (en) | 2005-07-16 | 2005-07-16 | Medical test device and method for optical analysis of an analyte |
DE102005033327.3 | 2005-07-16 |
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WO2007009541A1 true WO2007009541A1 (en) | 2007-01-25 |
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PCT/EP2006/005821 WO2007009541A1 (en) | 2005-07-16 | 2006-06-17 | Medical test device and method for the optical determination of an analyte comprising means for compensating the ambient light background |
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WO (1) | WO2007009541A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8299093B2 (en) | 2008-08-08 | 2012-10-30 | New York Blood Center, Inc. | Small molecule inhibitors of retroviral assembly and maturation |
CN103002799A (en) * | 2010-06-24 | 2013-03-27 | 日本先锋公司 | Photo-detection device and fluid measurement device |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11747197B2 (en) | 2021-09-15 | 2023-09-05 | Endress+Hauser Conducta, Inc. | Photometer and method of performing photometric measurements with a photometer |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4553848A (en) * | 1981-09-30 | 1985-11-19 | Boehringer Mannheim Gmbh | Method of detecting and evaluating photometric signals and device for carrying out the method |
US5117099A (en) * | 1989-09-01 | 1992-05-26 | Schmidt Terrence C | Ambient light rejecting quad photodiode sensor |
US5376783A (en) * | 1992-09-16 | 1994-12-27 | Ophir Optronics Ltd. | Power meter with background subtraction |
US5410145A (en) * | 1994-02-25 | 1995-04-25 | Coroy; Trenton G. | Light detector using reverse biased photodiodes with dark current compensation |
-
2005
- 2005-07-16 DE DE200510033327 patent/DE102005033327A1/en not_active Withdrawn
-
2006
- 2006-06-17 WO PCT/EP2006/005821 patent/WO2007009541A1/en active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4553848A (en) * | 1981-09-30 | 1985-11-19 | Boehringer Mannheim Gmbh | Method of detecting and evaluating photometric signals and device for carrying out the method |
US5117099A (en) * | 1989-09-01 | 1992-05-26 | Schmidt Terrence C | Ambient light rejecting quad photodiode sensor |
US5376783A (en) * | 1992-09-16 | 1994-12-27 | Ophir Optronics Ltd. | Power meter with background subtraction |
US5410145A (en) * | 1994-02-25 | 1995-04-25 | Coroy; Trenton G. | Light detector using reverse biased photodiodes with dark current compensation |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8299093B2 (en) | 2008-08-08 | 2012-10-30 | New York Blood Center, Inc. | Small molecule inhibitors of retroviral assembly and maturation |
US8546439B2 (en) | 2008-08-08 | 2013-10-01 | New York Blood Center, Inc. | Small molecule inhibitors of retroviral assembly and maturation |
CN103002799A (en) * | 2010-06-24 | 2013-03-27 | 日本先锋公司 | Photo-detection device and fluid measurement device |
EP2862510A1 (en) * | 2010-06-24 | 2015-04-22 | Pioneer Corporation | Light detecting apparatus and fluid measuring apparatus |
US9237856B2 (en) | 2010-06-24 | 2016-01-19 | Pioneer Corporation | Light detecting apparatus and fluid measuring apparatus |
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DE102005033327A1 (en) | 2007-01-25 |
WO2007009541A8 (en) | 2007-03-22 |
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