DE102005033327A1 - Medical test device and method for optical analysis of an analyte - Google Patents

Abstract

The invention relates to a medical test device for the optical measurement of a medically significant analyte in a sample of an aqueous liquid, in particular in blood, comprising a light source (5) for irradiating the sample with primary light (4), a signal light detector (10) which generates an analog measurement signal generated, which characterizes the intensity of detected light, the signal light detector (10) being arranged for the detection of secondary (6), which is created by the interaction of primary light (4) with the sample, an background light detector (13) which generates an analog background signal , which characterizes the intensity of detected light, wherein the background light detector (13) is arranged for the detection of ambient light (9) which can contain primary light (4), an evaluation means (15) for evaluating the signal light detector (10) and the background light detector (13) generated signals to detect the analyte in the sample and / or its concentrates on to determine. To compensate for the portion of the measurement signal caused by ambient light (9) which is detected by the signal light detector (10) together with secondary light (6), the signal light detector (10) and the background light detector (13) are connected to a common line (14), which leads to the evaluation means (15), connected so that the analog signals generated by the light detectors (10, 13) are subtracted from one another and a compensated analog signal is produced which ...

Description

The The invention relates to a medical test device and a method for optical Measurement of a medically significant analyte in a sample of a aqueous liquid, especially in blood.

The quantitative determination of chemical and biochemical components colored aqueous liquids, especially colored biological fluids such as blood or urine, and products from biological fluids such as blood serum and Blood plasma, is for medical applications such as the diagnosis and treatment of diseases of steadily increasing importance. Usually will a body fluid as blood or urine with a handheld device and associated test strips examined. The test strip has a reaction zone impregnated with reagents, those with an analyte of the liquid react while changing the color cause. The color change can be quantitatively evaluated by photometric analysis. A widely used application is the measurement of blood glucose content of diabetics.

For such Applications need Photometric signals are detected and evaluated with very high precision. The measuring signals however are common in relation to too much noise and unwanted signal components weak. Typically, that must Measuring signal to a factor of at least 1000 will be amplified to make it from the Noise and the interfering signals can be separated.

Dry and biochemical components of aqueous liquids may also quantitatively determined by the examination of fluorescent light become. An occurring between fluorescent light and excitation light Wavelength shift makes it easier, the fluorescent light from the excitation light, for example, by using suitable filters to separate, however Fluorescence signals are much weaker than photometric signals. This adds the need for very high precision strengthened the measurement and evaluation.

The in electronic terms, in amplifying extremely weak signals Problems encountered include amplifier fluctuations, voltage contributions from different ones Components, high and low frequency noise and leakage and residual currents of various Art. These problems of measuring and Evaluation electronics are due to the influence of ambient light on the Measurement itself amplified. Included in this context the term ambient light from external sources such as the sun or light bulbs as well as stray light from an internal light source, which is the detector achieved without interaction with the sample.

In the US 4,553,848 describes a test device that addresses this and related problems.

The known device has a measuring photodiode for detecting secondary light, caused by interaction of primary light with the sample, and a reference photodiode for detecting ambient light. A measuring and integration circuit alternately evaluates signals of the measuring photodiode and the reference photodiode off. The signals are integrated and subsequently digitized. The influence of Ambient light on the measurement is given numerically by a microprocessor Compensated, from a digitized value, to integrated Signals of the measuring photodiode based, and a Referenzmeßwert, which is based on integrated signals of the reference photodiode, a Quotient calculated. The light source of the device is at predetermined time intervals switched on and off. Signals of the photodiodes are in the same Evaluated way in the lighting phase and the dark phase. By subtracting results of the dark phase of results The lighting phase can be noise and noise components significantly reduce.

however leads one progressive reduction of sample volumes in the interest of a Minimizing pain and discomfort in blood glucose measurements to an increasingly unfavorable Signal-to-noise ratio, so that With handheld devices known in the art, readings are no longer with the desired precision can be determined. The object of the present invention is therefore to a test device to disposal to provide an improved suppression and / or compensation of undesirable signal posts as ambient light allows.

This object is achieved by a medical test device for optical measurement of a medically significant analyte in a sample of an aqueous liquid, in particular in blood, comprising: a light source for irradiating the sample with primary light, a signal light detector which generates an analog measurement signal which determines the intensity of characterized in that the signal light detector is arranged to detect secondary light produced by interaction of primary light with the sample, a background light detector which generates an analog background signal which characterizes the intensity of detected light, the background detection sub-detector is arranged, which may contain primary light, evaluation means for evaluating the signals generated by the signal light detector and the background light detector to detect the analyte in the sample and / or to determine its concentration, characterized in that for compensating the by ambient light emitted by the Signal light detector is detected together with secondary light, caused proportion of the measurement signal of the signal light detector and the background light detector so connected to a common line leading to the evaluation, are connected, that the analog signals generated by the light detectors are subtracted from each other and a compensated analog signal is formed, the evaluation is supplied.

These Task is further solved by a method of optically measuring a medically significant one Analytes in an aqueous fluid sample, especially in blood, with a medical testing device the following steps: irradiating the sample with primary light, Respectively of secondary light, caused by interaction of primary light with the sample, to a signal light detector, which is an analog measurement signal that generates the intensity characterized the detected light, detecting ambient light, contain the primary light can, by means of an underground light detector, the an analog underground signal that generates the intensity characterized by ambient light, evaluation of the measured signal and the background signal to detect and / or detect the analyte in the sample to determine its concentration, characterized in that the measuring signal and the background signal are subtracted from each other, so that a compensated Analog signal is generated, which then for detection and / or determination the concentration of the analyte in the sample is evaluated.

By The present invention solves the problem that the signal light detector of a test apparatus is inevitable Ambient light as well as secondary light, which results from interaction with the sample detected. consequently contains the measurement signal generated by the detector always has a share, based on ambient light. This inevitable contribution must be compensated be so for the medical applications required precision can be achieved. Instead of the influence of To compensate for ambient light through calculations that are complex Mathematical algorithms are based on the present invention a compensation of ambient light on simple, accurate and achieved efficient manner before the measurement signal digitized and with the evaluation is evaluated.

Of the Signal light detector and the background light detector generate at Detection of light in each case an analog signal, which is usually around is an electric current, but also a voltage can be. The measurement signal generated by the signal light detector contains a useful portion caused by secondary light originating from the sample will, and an unwanted portion, which is caused by ambient light. The background signal is based Completely on ambient light. By overlaying These signals are subtracted from each other, so that an analog signal arises, which contains in principle only the portion of the measuring signal, the was caused by secondary light originating from the sample.

On this way can be achieve with the invention, an ambient light compensation, both simple as well as very precise is.

Further Details and advantages of the invention will be made in the following of exemplary embodiments with reference to the attached Drawings explained. Identical and corresponding parts are by matching Reference numbers marked. The features shown therein can be individually or used in combination to further preferred embodiments to provide the invention. Show it:

1 an example of the operation of a medical testing device;

2 an example of the circuit of a medical testing device according to the invention;

3 another example of a circuit of a medical testing device according to the invention;

4 another example of a circuit of a medical testing device according to the invention;

5 an example of an optical fiber of a medical testing device according to the invention; and

6 another example of a circuit of a medical testing device according to the invention.

1 exemplifies the operation of a medical test device. A sample of an aqueous fluid to be tested is placed on a test field 1 at one end of a measuring channel 2 a multi-channel optical fiber 3 arranged. The sample comes with primary light 4 irradiated by a light-emitting diode 5 that ver as light source ver is used, aired. By interaction of the primary light 4 with the sample on the test field 1 creates secondary light 6 passing through the measuring channel 2 the fiber 3 to a signal light detector 10 which is at the other end of the measuring channel 2 the fiber 3 is arranged. The multi-channel fiber 3 further comprises a reference channel 11 to ambient light 9 from a reference surface 12 in the neighborhood of the test field 1 to a background light detector 13 to lead. To minimize signal mixing between the channels, the reference channel 11 from the measuring channel 2 through a separating layer 19 separated. Inevitably, the signal light detector receives 10 also ambient light 9 that needs to be compensated. Preferably also the reference field 12 covered with sample.

The test field 1 is preferably part of a test strip for examination at one end of the measuring channel 2 is arranged. Preferably, the test strip is close to the test field 1 a reference field, as in 1 by the reference number 12 is indicated. The measuring channel 2 and the reference channel 11 the optical fiber 3 may also be formed as individual optical fibers.

The example shown is the secondary light 6 either light reflected from the sample or, preferably, fluorescent light. Of course, it is also possible to transmit transmitted light as a secondary light with the signal light detector 10 to measure and the primary light 4 to the test field 1 and the reference field 12 to conduct by means of another optical fiber.

The signal light detector 10 provides an analogue measuring signal, which is the intensity of the detected light, that is secondary light 6 and ambient light 9 exists, characterized. The underground light detector 13 provides an analog background signal that characterizes the intensity of detected light and is capable of detecting ambient light 9 arranged. For a precise measurement, the proportion of the measurement signal, the ambient light 9 is compensated.

2 shows an example of the electronic circuit with which such compensation can be achieved. In the example shown, diodes, in particular PIN diodes, are used as signal light detectors 10 and background light detector 13 used. The light detectors 10 . 13 each provide an analog signal, ie, an electrical current that is approximately proportional to the intensity of the detected light. The light detectors 10 . 13 are of opposite polarity to a common line 14 connected to the evaluation means 15 leads. Therefore, the from, the signal light detector flow 10 electric current generated as a measurement signal and that of the background light detector 13 electric current generated as background signal on the common line 14 in opposite directions. In this way, the measurement signal and the background signal are superimposed and subtracted from each other, so that a compensated analog signal is produced in the influences of the ambient light 9 are compensated and that the evaluation 15 is forwarded.

The compensated analog signal consists essentially of the portion of the measuring current caused by detected secondary light. The remainder of the measuring current caused by ambient light 9 was caused, and the reference current cancel each other out.

The described compensation of the influence of ambient light obviously works best when the two light detectors 10 . 13 receive exactly the same amount of ambient light. This can be achieved by a suitable arrangement of the background light detector 13 and the signal light detector 10 be achieved. For example, the light detectors 10 . 13 in an optical reference fiber 11 or an optical measuring fiber 2 embedded, each having the same transmission values. Furthermore, the characteristics, ie the strength of the current generated as a result of a given light intensity, of the signal light detector should be 10 and the underground light detector 13 be as identical as possible.

For this reason, it is the signal light detector 10 and the background light detector 13 preferably semiconductor devices, since these can be easily manufactured within close tolerances. Preferably, the signal light detector 10 and the background light detector 13 arranged on a common semiconductor substrate, for example as PIN diodes. Other semiconductor devices such as phototransistors or photoresistors can also be used as light detectors 10 ; 13 be used. Semiconductor devices which have a barrier layer in which electrons can be excited by absorption of light from a valence band into a conduction band are the most suitable for the invention.

The compensated signal produced by superimposing and subtracting the measurement signal and the background signal becomes a current-voltage converter 16 which generates a voltage equal to the magnitude of the electric current in the common line 14 is proportional. Consequently, the voltage is also proportional to the intensity of the detected secondary light, as long as the characteristic of the signal light detector is perfectly linear.

So that any nonlinearities of the characteristic of the signal light detector 10 Getting corrected can, must the intensity of ambient light 9 be determined. Nonlinearities of the characteristic are usually based on saturation effects. This means that as the intensity of the detected light increases, the additional current generated as a result of a given increase in the intensity of the detected light decreases.

If the intensity of the ambient light and the characteristic curve of the light detectors are known, a nonlinearity of the characteristic curve can be determined by the evaluation means 15 be compensated.

The intensity of ambient light 9 can with a third light detector 17 according to 2 be measured. That of the third light detector 17 generated electrical current is transformed into a current-voltage converter 18 fed so that the resulting voltage for the intensity of ambient light 9 is characteristic. This voltage becomes the evaluation means 15 supplied, which is preferably a microprocessor, the influences of nonlinearity of the characteristic of the signal light detector by numerical calculations 10 compensated.

3 shows an example of another circuit, with which also an ambient light compensation is achieved. As with the basis of 2 In game are the signal light detector described 10 and the background light detector 13 with opposite polarity to the common line 14 connected so that of the signal light detector 10 measuring current generated by the measuring signal and that of the background light detector 13 superimposed reference current generated as background signal and subtracted from each other. In this way, an analog signal is generated, which is the evaluation means 15 is supplied.

In the 3 The circuit shown comprises a switch 20 with which the signal light detector 10 from the common line 14 can be disconnected so that the background light detector 13 the evaluation means 15 An analog signal provides the intensity of the ambient light 9 equivalent. In this way, the evaluation means 15 that for the correction of nonlinearities of the characteristic of the signal light detector 10 required information about the intensity of the ambient light can be made available. Preferably, the intensity of the ambient light 9 measured both before and after the measurement of the intensity of the secondary light. By averaging over the intensities of the ambient light measured before and after the intensity of the secondary light, influences of possible fluctuations in the intensity of the ambient light can be minimized.

Usually, the intensity of the ambient light 9 much larger than the intensity of fluorescent light (secondary light 6 ). As a result, it changes over the shared line 14 to the current-voltage converter 16 flowing electricity drastically when the switch 20 opened or closed. To a saturation of the current-voltage converter 16 to prevent its gain should be adjusted, what with the switch 21 is possible.

4 shows another example of a circuit for a medical test device according to the invention. In this example, the signal light detector comprises a PIN diode 10 and a connected current-voltage converter 16 , The signal light detector 10 . 16 Therefore provides an analog measurement signal in the form of a voltage which is proportional to the current generated by the PIN diode because of detected light. In the same way, the background light detector comprises a PIN diode 13 and a current-voltage converter 22 , In this way, the background light detector provides 13 . 22 an analog underground signal in the form of a reference voltage.

The signal light detector 10 . 16 and the background light detector 13 . 22 are to the inputs of a differential amplifier 23 connected. The output of the differential amplifier 23 is to the common line 14 connected to the evaluation means 15 leads. The differential amplifier 23 subtracts the difference voltage from the measurement voltage and amplifies the result. In this way, a compensated analog signal in the form of the output voltage of the differential amplifier 23 generated. The output voltage is proportional to the intensity of the secondary light 6 , provided the characteristic of the signal light detector 10 is perfectly linear. Possible non-linearities can be compensated by using a third light detector, as determined by 2 is described.

5 shows an example of an optical measuring fiber 2 a medical testing device according to the invention. In 5 is also the arrangement of the signal light detector 10 and the light source 5 with regard to the measuring fiber 2 shown. As already on the basis of 1 has been explained, will be primary light 4 from the light emitting diode used as a light source 5 sent. By interaction of primary light 4 with one in the test field 1 at the end of the optical fiber 2 arranged sample creates secondary light 6 , secondary light 6 gets along with ambient light 9 through the measuring fiber 2 to the signal light detector 10 directed. The effect of primary light 4 on the signal light detector 10 can be minimized by adding primary light 4 into the measuring fiber 2 through a diversion 2a the measuring fiber 2 is fed. Preferably, the primary light enters the optical fiber 2 at an angle of 20 ° to 25 °.

Of course, an optical reference fiber may be parallel to the optical signal fiber 2 be arranged as it is in 1 is shown.

Preference is given to several signal fibers 2 each with its own light source 5 used. The test field 1 on which the sample is applied, can then be divided into smaller sub-areas, each by means of a signal fiber 2 be examined as it is in 5 is shown. If the results of these sub-areas differ by more than one critical value, it can be concluded that the test field 1 only partially covered with the sample. In this case, no precise measurement is possible. A user of the device becomes aware of this fact by the evaluation means 15 made aware of a suitable signal, for example with a warning light or an acoustic signal.

Each signal fiber is preferred 2 a reference fiber 11 assigned. 6 shows an example of the circuit for such a bundle of signal fibers 2 and reference fibers 11 , Every signal fiber 2 directs light to a signal light detector 10 and every reference fiber 11 directs light to a background light detector 13 , When different light sources 5 for irradiating different parts of the test field 1 can be used with increased reliability, determine whether the test field 1 correctly covered with a sample.

For example, if two light sources 5 that are connected to different signal fibers 2 connected and therefore different signal light detectors 10 are assigned, with different frequencies or phase-shifted on and off and the common line 14 connected to lock-in amplifiers for these frequencies, the output signals of the lock-in amplifiers can be compared. If the output signals are significantly different then it is very likely that one of the signal light detectors 10 contains much less secondary light than the other. This means that the corresponding part of the test field 1 not or only partially covered with sample. In this way, a user can be made aware that the sample was not applied correctly.

The number of signal light detectors 10 and the number of background light detectors 13 does not necessarily have to match. It is sufficient if all background light detectors 13 together the same amount of ambient light 9 like all signal light detectors 10 get together. For example, a single optical measuring fiber 2 leading to a single signal light detector, along with two reference optical fibers 11 used, each to a background light detector 13 lead, if the cross-sectional area of the measuring fiber 2 is as large as the cross-sectional area of the two background light detectors 13 together.

The evaluation means 15 to which the joint leadership 14 is connected, preferably comprises a microprocessor, which is programmed according to the prior art. Details are in the US 4,553,848 and US 5,463,467 disclosed. In particular, it is advantageous to switch the light source on and off at a relatively high frequency and to use lock-in amplifiers for amplification, which may be part of the evaluation means.

Claims (17)

Medical test device for the optical measurement of a medically significant analyte in a sample of an aqueous fluid, in particular in blood, comprising: a light source ( 5 ) for irradiating the sample with primary light ( 4 ), a signal light detector ( 10 ) which generates an analog measurement signal which characterizes the intensity of detected light, wherein the signal light detector ( 10 ) for the detection of secondary light ( 6 ) arranged by interaction of primary light ( 4 ) with the sample, a background light detector ( 13 ) which generates an analog underground signal which characterizes the intensity of detected light, wherein the background light detector ( 13 ) for the detection of ambient light ( 9 ), the primary light ( 4 ), an evaluation means ( 15 ) for evaluating the signal light detector ( 10 ) and the background light detector ( 13 ) to detect the analyte in the sample and / or to determine its concentration, characterized in that to compensate for the ambient light ( 9 ) detected by the signal light detector ( 10 ) together with secondary light ( 6 ) is detected, caused fraction of the measurement signal of the signal light detector ( 10 ) and the background light detector ( 13 ) to a common line ( 14 ), which belong to the evaluation means ( 15 ), are connected, that of the light detectors ( 10 . 13 ) are subtracted from each other and a compensated analog signal is formed, which the evaluation means ( 15 ) is supplied. Apparatus according to claim 1, characterized in that both the signal light detector ( 10 ) as well as the background light detector ( 13 ) each include a semiconductor device, wherein detecting light causes the generation of an analog signal. Apparatus according to claim 2, characterized in that the semiconductor component of the signal lightde tector ( 10 ) and the semiconductor device of the background light detector ( 13 ) are arranged on a common semiconductor substrate. Apparatus according to claim 2 or 3, characterized in that the signal light detector ( 10 ) and the background light detector ( 13 ) each have a barrier layer in which electrons can be excited from a valence band into a conduction band by light absorption. Apparatus according to claim 4, characterized in that the signal light detector ( 10 ) and the background light detector ( 13 ) each comprise a diode, preferably a PIN diode. Device according to one of the preceding claims, characterized in that the signal light detector ( 10 ) at one end of an optical measuring fiber ( 2 ) arranged to serve the secondary light ( 6 ) from the sample to the signal light detector ( 10 ). Apparatus according to claim 6, characterized in that the background light detector ( 13 ) at one end of an optical reference fiber ( 11 ) arranged to conduct ambient light ( 9 ) from an environment ( 12 ) of the input of the optical measuring fiber to the background light detector ( 13 ) is arranged. Apparatus according to claim 7, characterized in that the optical measuring fiber ( 2 ) and the optical reference fiber ( 11 ) as separate channels of a multi-channel fiber ( 3 ) are formed. Device according to one of the preceding claims, characterized in that the evaluation means ( 15 ) Comprises memory means in which a characteristic of the signal light detector ( 10 ) is stored, wherein the characteristic of the evaluation ( 15 ) is used to influence the intensity of the ambient light ( 9 ) on the proportion of the measuring signal, which on detected secondary light ( 6 ) is due to compensate. Apparatus according to claim 9, characterized in that the intensity of the ambient light ( 9 ) with a third light detector ( 17 ) is measured, which to the evaluation means ( 15 ) connected. Apparatus according to claim 9, characterized in that it has a switch ( 20 ), with which the signal light detector ( 10 ) from the common line ( 14 ) can be separated so that the underground light detector ( 13 ) the evaluation means ( 15 ) provides an analog signal that matches the intensity of the ambient light ( 9 ) corresponds. device according to one of the preceding claims, characterized that this measuring signal and the background signal are electrical currents. Device according to one of the preceding claims, characterized in that the signal light detector ( 10 ) and the background light detector ( 13 ) to the common line ( 14 ) are connected with opposite polarity. Device according to one of the preceding claims, characterized in that the signal light detector ( 10 ) and the background light detector ( 13 ) to the inputs of a differential amplifier ( 23 ) and the output of the differential amplifier ( 23 ) to the common line ( 14 ) connected. Device according to one of the preceding claims, characterized in that it is in the secondary light ( 6 ) is fluorescent light. device according to one of the preceding claims, characterized that it a handset is. Method for the optical measurement of a medically significant analyte in a sample of an aqueous liquid, in particular in blood, with a medical test device, comprising the following steps: irradiation of the sample with primary light ( 4 ), Supplying secondary light ( 6 ) caused by the interaction of primary light ( 4 ) with the sample, to a signal light detector ( 10 ), which generates an analog measurement signal that characterizes the intensity of the detected light, detecting ambient light ( 9 ), the primary light ( 4 ) with a background light detector ( 13 ), which generates an analog underground signal that measures the intensity of ambient light ( 9 ), evaluating the measurement signal and the background signal to detect the analyte in the sample or to determine its concentration, characterized in that the measurement signal and the background signal are subtracted from each other, so that a compensated analog signal is formed, which then for detection and / or the determination of the concentration of the analyte in the sample is evaluated.