Measuring arrangement for determining at least one parameter of a blood sample

Measurement arrangement for the determination of at least one parameter of a blood sample

The invention relates to a measurement arrangement for the determination of at least one parameter of a blood sample, composed of a flow measuring cell in which at least one luminescent optical sensor element is disposed that can be contacted. with the blood sample, at least one light source for the excitation of the optical-luminescent sensor element and at least one photodetector for recording the luminescent radiation emitted by the optical-luminescent sensor element, the light source and the photodetector being arranged on opposite sides of the flow measurement cell.

EP 0 175 352 B1 has disclosed a procedure and an arrangement for the rapid measurement of the parameters of a sample medium. The arrangement has a flow measurement cell for gases and liquids, whereby a simultaneous determination of multiple parameters is possible, a transparent luminescent sensor layer being in the flow cell in contact with the sample. As measurement quantities, the concentration of oxygen and temperature are mentioned, the luminescent radiation being measured at 650 nm or 720 nm and the excitation radiation having a shorter wavelength. The excitation radiation is produced by means of LEDs and the detection of radiation by means of photodiodes, which are located on opposite sides of the flow measuring cell. The luminescent sensing layer is arranged on the detection side, so that the excitation radiation must pass through the test medium on its way to the luminescent sensing layer. This fact is presented as a disadvantage in absorbent liquids, such as blood, since the excitation radiation would be considerably weakened by the measuring means.

In addition, from EP 1 130 382 B1 an optical sensor is known for testing multiple analytics of a sample fluid, in which a plurality of optical sensors is in contact with the sample fluid. The device has light sources for the provision of excitation radiation and detectors for the determination of the light interaction by means of the sensors, there is a processor that from the measured light interactions determines each of the analytes in the liquid of sample. The sensor is used among others for the measurement of blood glucose, also determining the concentration of O2 and the temperature.

Measurement arrangements are also known (EP 1 106 987 B1) in which two optical components (light source and detectors) can contact the sensing layer in the flow measuring cell from one side, being parts of the measuring cells transparent and used as light conductors for measuring radiation and excitation radiation.

From WO 2002/059585 A2 a measurement arrangement is known for determining the concentration of oxygen in a gas, for example in the respiratory air. The measurement arrangement has a flow measurement cell in which an optical-luminescent sensor element that contacts a gas flow is arranged. As possible measurement geometries, two reflection geometries are exposed, in which the radiation source of the excitation radiation and the detector for the registration of the luminescent radiation are located on the same side of the flow measurement cell. In addition, a transmitted light geometry is described in which the optical-luminescent sensor element is disposed on the detector side of the flow measuring cell.

It is the object of the invention to achieve improvements in the signal quality of the measurement radiation in a measurement arrangement for the determination of at least one parameter of a blood sample, the measurement arrangement being economical and simple to manufacture.

This objective is achieved, according to the invention, because the at least one luminescent optical sensor element is arranged on the excitation side of the flow measuring cell facing the light source, because the light source emits radiation of excitation less than 600 nm, for example 425 nm and the luminescent radiation of the optical-luminescent sensor elements is in a wavelength band greater than 600 nm, whereby the excitation radiation is exposed to a much stronger absorption than the luminescent radiation through the blood sample.

The invention takes advantage of the fact that in the absorption of radiation the blood has a very high dependence on the wavelength that, for example, is shown in the illustration according to figure 5. In this representation, both for oxygenated blood (continuous line ) as for deoxygenated blood (dashed line) the absorption μa is represented as a function of the γ wavelength. The diagram comes from Faber et al: "Oxygen Saturation-Dependent Absorption and Scattering of Blood"; Physical Review Letters, 2004 and addresses the differences in the absorption behavior of oxygenated and deoxygenated blood. In this diagram it is evident that, for example, an excitation radiation λA in the 425 nm band is absorbed into the blood much more than the luminescent radiation λL emitted by the optical sensors in the 780 nm band. In the illustrated example, the excitation light is approximately weakened by the factor 100 with respect to the luminescent light. According to the invention, by means of the arrangement of the optical-luminescent sensor elements it happens that on the excitation side of the

flow measurement cell the blood sample serves as a filter for excitation radiation and preferably The luminescent radiation emitted by the sensor elements reaches the photodetectors.

According to the invention, the optical sensor elements are arranged on the excitation side of the cell of flow measurement, preferably in a linear arrangement along the axis of the measuring cell, being assigned to each sensor element a light source and on the opposite measurement side of the flow measurement cell a photodetector Another advantage compared to the current state of the art, for example EP 0 175 352 B1, it consists in that the flow measuring cell can be inserted in a two-part measuring sleeve, whose excitation part contains the light sources, preferably LEDs, together with the electronic excitation system and whose measurement part contains the photodetectors, preferably photodiodes, together with the electronic system measurement. Consequently, light sources and detectors are in separate control circuits spatially, so the electronic influence of the different components is prevented. In this case, the blood sample is transparent enough only for wavelengths greater than 600 nm, radiation excitation is found in shorter wavelengths, for example 425 nm. According to an advantageous configuration of the invention, the excitation side of the flow measuring cell it presents in the sector of the optical-luminescent sensor elements a reflective, transparent layer for the Excitation radiation and reflecting the luminescent radiation. With the help of the reflective layer, the parts of radiation of the luminescent radiation emitted in the direction to the light source are diverted to the photodetector and, of In this way, they reinforce the net signal. In the case of a phase measurement, on the excitation side of the cell measurement is arranged at least one reference light source whose reference radiation penetrates the cell of flow measurement and reaches the photodetectors arranged on the opposite measurement side.

Next, the invention is explained in detail by drawings. They show: Figure 1, in schematic longitudinal section, a first variant embodiment of a measurement arrangement for the determination of at least one parameter of a blood sample;

Figure 2, in a sectional representation according to Figure 1, a second embodiment variant of the arrangement measurement;

Figures 3 and 4, detailed representations of measurement arrangements according to Figures 1 and 2; as well as

Figure 5, the diagram of absorption of a blood sample in the range of a wave band λ von 200 nm at 1,000 nm.

The measurement arrangement shown in Figure 1 for the determination of at least one parameter of a sample of blood has a flow measurement cell 1 in which, for example, three are arranged optical-luminescent sensor elements ST (temperature), SO (oxygen) and SG (glucose) that during the measurement They are put in contact with the blood sample. The flow measurement cell 1 is arranged so replaceable in a two-part measuring sleeve 2 (plugged in or crimped), whose excitation part 3 Contains the light sources 4 assigned to the different sensor elements and excitation filters 12a to 12c together with the electronic excitation system (not shown), containing the measuring part 5 of the measuring sleeve 2 the photodetectors 6 and measurement filters 13a to 13c together with the electronic measurement system. Light source 4 and the photodetectors 6 are arranged on opposite sides 7, 8 (excitation side 7 and measuring side) of the cell Flow measurement 1.

Because the optical, luminescent sensor elements ST, SO and SG are arranged on the excitation side 7 of the flow measurement cell 1 facing the light source 4, both the luminescent radiation L generated in the optical-luminescent sensor element L as a part of the excitation radiation A penetrates the sample of blood. The excitation radiation A is weakened to a much greater extent by absorption in the blood sample that the luminescent radiation of greater wavelength, so that through the sample an effect is produced Positive filter for measurement that improves signal quality.

The optical, luminescent sensor elements ST, SO, SG are preferably arranged in an arrangement linear along the axis of the measuring cell 1 ', with each sensor element assigned a light source 4 and a photodetector 6 on the measurement side 8 of the flow measurement cell 1.

By means of the measurement arrangement outlined in Figure 1, for example, a measurement of the dimming time, that is the dimming time of the luminescence intensity measured after the excitation of the optical-luminescent sensor elements is a measure for the magnitude of measurement.

As shown, for example, Figure 1, the excitation side 7 of the flow measuring cell 1 may have in the sector of the optical-luminescent sensor elements ST, SO, SG a reflective layer 9, the effect being of the reflective layer shown by Figures 3 and 4. The excitation radiation A impacts on the element ST, SO or SG optical-luminescent sensor, whereby luminescent radiation L is released in all directions

Space Without a reflective layer (see Figure 3), the radiation parts emitted in the direction of the light source are no input to the measurement signal.

With the fixation of a reflective layer (see Figure 4), transparent for radiation of a wavelength less than 600 nm and radiation reflective of a wavelength greater than 600 nm, parts of the luminescent radiation L are reflected , additionally, to the detector and reinforce the measurement signal.

By means of the measurement arrangement outlined in Figure 2, for example, a phase measurement can be performed for which a reference signal must be obtained for the reference of the measurement signals. According to the invention, on the excitation side 7 of the flow measuring cell 1, at least one reference light source 10 and / or 11 is arranged, whose reference radiation R1, R2 penetrates the flow measuring cells 1 and is detected by the photodetectors 6 arranged on the opposite measurement side 8. For example, a first reference light source 10 may be provided with a reference radiation R1 in the 620 nm band and a second reference light source 11 with a reference radiation R2 in the 780 nm band, which are preferably arranged , in the excitation part 3 of the two-part measuring sleeve 2. In the reflective layer 9 on the excitation side 7 of the flow measurement cell 1, holes 14 are provided through which the reference radiation can penetrate the flow measurement cell 1.

Both in figure 1 and in figure 2 are arranged between the light sources 4 and the optical-luminescent sensor elements ST, SO, SG excitation filters 12a, 12b and 12c, the light sources 4 also being able to be embedded in a filter layer 12` common. In addition, measurement filters 13a, 13b and 13c are arranged on the input side of the photodetectors 6.

The LEDs of the light source 4 can emit, for example, an excitation radiation of less than 600 nm, for example 425 nm, the luminescent radiation of the optical-luminescent sensor elements ST, SO, SG being in a band of length wavelength greater than 600 nm, for example 780 nm.

In summary, the advantages of the measuring device according to the invention consist in:

<dl><dt>•</dt><dd> a very simple optical structure; </dd></dl>

<dl><dt>•</dt><dd> a flat design of the flow measuring cell 1 and measuring sleeve 2; </dd></dl>

<dl><dt>•</dt><dd> high signal intensity, because photodetectors can be made larger; </dd></dl>

<dl><dt>• </dt><dd>no electrical crosstalk (minimum background signals), because there is a spatial separation between the excitation part 3 and the measuring part 5 of the measuring sleeve 2; </dd></dl>

<dl><dt>•</dt><dd> by measuring the signal strength, the sample is identified (blood sample or cleaning fluid); </dd></dl>

<dl><dt>•</dt><dd> simultaneous photometric characterization of the blood sample (hemoglobin content and oxygenation); </dd></dl>

<dl><dt>•</dt><dd> a parallel determination of arterial PO2.</dd></dl>