Method and sensor for determining a value indicative of the impedance of a suspension

DE502019013887D1Active Publication Date: 2025-10-02HAMILTON BONADUZ AG
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Patent Information

Application Number
DE502019013887
Authority / Receiving Office
DE · DE
Patent Type
Patents
Current Assignee / Owner
Priority Date
2018-11-30
Filing Date
2019-11-29
Publication Date
2025-10-02
Estimated Expiration
2039-11-29

AI Technical Summary

Technical Problem

Current impedance spectroscopy methods for suspensions, particularly cell suspensions, suffer from inaccuracies and variability in measurement results over a wide frequency range, necessitating improved methods and sensors for reliable and accurate impedance determination.

Method used

A method and sensor using multiple measuring electrodes and correction functions to calculate impedance values, accounting for geometric and interference factors, combined with sampling and Fourier transforms to enhance measurement accuracy and minimize noise.

Benefits of technology

The method and sensor provide high-accuracy impedance measurements across a wide frequency range, enabling precise determination of cell population properties such as cell number, size, and homogeneity.

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Description

[0001] The present invention lies in the field of impedance spectroscopy of suspensions, in particular cell suspensions. In particular, the present invention relates to determining the impedance of a suspension or determining a value indicative of the impedance of a suspension. Furthermore, the present invention particularly relates to a method and a sensor for determining a value indicative of the impedance of a suspension.

[0002] Electrical impedance spectroscopy methods are used as a measurement technique for the non-destructive in-situ and in-vivo determination of frequency-dependent passive electrical properties of suspensions. The term "suspension" refers to the distribution of small particles of a substance or mixture of substances in a liquid. An example of a suspension analyzed using electrical impedance spectroscopy methods is a substance from a liquid and the biological cells suspended therein, collectively referred to herein as a cell population. The aforementioned frequency-dependent passive electrical properties of the cell population can provide information about, among other things, the number of living cells and / or the size of the cells and / or the homogeneity of the cells.

[0003] Rahman ARA et al., "Cell culture monitoring by impedance mapping using a multielectrode scanning impedance spectroscopy system (CellMap)," Physiological Measurement, Institute of Physics Publishing, Bristol, UK, Vol. 29, No. 6, June 1, 2008, discloses an impedance sensor system that can map the cell distribution in a cell culture chamber by recording the impedance at different locations. A radial electrode array is used. This enables multidimensional characterization of the cell cultures.

[0004] Current sensors and impedance spectroscopy methods are not always entirely satisfactory in terms of measurement accuracy. Furthermore, the quality of the measurement results can vary considerably over a wide frequency range.

[0005] Accordingly, it would be desirable to provide a method and a sensor for determining a value indicative of the impedance of a suspension that has a high measurement accuracy and enables reliable measurements over a wide frequency range.

[0006] The invention comprises a method for determining a value indicative of the impedance of a suspension according to claim 1 and claim 8, and a sensor for determining a value indicative of the impedance of a suspension according to claim 12 and claim 16. Further embodiments are contained in the dependent claims.

[0007] The method comprises the steps of determining a first impedance measurement value based on the excitation current and a first voltage at a first pair of measuring electrodes and determining a second impedance measurement value based on the excitation current and a second voltage at a second pair of measuring electrodes. The first and second pairs of measuring electrodes are different pairs, i.e. the first and second pairs of measuring electrodes differ in at least one measuring electrode. This in turn means that the sensor used has at least three measuring electrodes. The first voltage and the second voltage are thus measurement values ​​for different cell geometries, i.e. measurement values ​​for different measuring cells in the suspension. The term measuring cell refers to the totality of all influences of the suspension on the arrangement of two specific measuring electrodes.The terms "first voltage" and "second voltage" refer specifically to a first measured voltage and a second measured voltage. Determining the first impedance measurement may include a first voltage measurement, and determining the second impedance measurement may include a second voltage measurement.

[0008] The term suspension describes a distribution of particles in a liquid. In particular, the term suspension refers to a suspension with particles with an impedance > 0. The particles can be non-living particles, such as carbon particles. But they can also be living or partially living particles, such as cells. The suspension can be a cell population. The term cell population is used herein for a collection of biological cells in a carrier liquid. In particular, the term cell population is used for collections of biological cells that have a significant proportion of living cells. By determining one or more values ​​​​indicating the impedance of the suspension, conclusions can be drawn about one or more properties of the suspension.

[0009] According to a further embodiment, the first pair of measuring electrodes consists of a first measuring electrode and a second measuring electrode, and the second pair of measuring electrodes consists of the first measuring electrode and a third measuring electrode. In other words, the first pair of measuring electrodes and the second pair of measuring electrodes consist of a total of three measuring electrodes. In this way, two pairs of measuring electrodes can be provided with a minimal total number of measuring electrodes. This allows the method to be carried out with a sensor comprising few components.

[0010] According to a further embodiment, the first pair of measuring electrodes consists of a first measuring electrode and a second measuring electrode, and the second pair of measuring electrodes consists of a third measuring electrode and a fourth measuring electrode. In this way, the first pair of measuring electrodes and the second pair of measuring electrodes are independent of one another. The measurements on the first pair of measuring electrodes and the second pair of measuring electrodes can be carried out separately. They can also be carried out simultaneously, depending on the downstream signal processing. Separating the two pairs of measuring electrodes can simplify downstream signal processing. Furthermore, the geometry of the measuring cell of the first pair of measuring electrodes and the geometry of the measuring cell of the second pair of measuring electrodes can have a higher degree of independence than in the previously mentioned case of a total of three measuring electrodes.In this way, it may be possible to remove interference from the measurement results even more effectively.

[0011] According to the invention, determining the value indicating the impedance of the suspension comprises calculating the difference between a first adjusted impedance value and a second adjusted impedance value, wherein the first adjusted impedance value and the second adjusted impedance value are obtained by applying a correction function to the first impedance measured value and the second impedance measured value. Calculating the difference represents a relatively simple but effective measure for eliminating a significant proportion of the interference influences on the measured values. Thus, with relatively little computational effort, a significant improvement in the measurement accuracy of the value indicating the impedance of a suspension can be achieved. The above-mentioned correction function can map the transfer behavior of the measuring arrangement. In this way, the influence of the measuring arrangement on the measured signals, such as additional signal propagation times, amplification, losses, etc., can be taken into account.

[0012] According to a further embodiment, determining the value indicating the impedance of the suspension comprises calculating the difference between a first geometry factor and a second geometry factor, wherein the first geometry factor represents the measurement geometry of the first pair of measuring electrodes and wherein the second geometry factor represents the measurement geometry of the second pair of measuring electrodes. By calculating the difference, the different geometric arrangements of the two pairs of measuring electrodes can be taken into account in a simple but effective manner. The fact that the use of different pairs of measuring electrodes means that the first impedance measurement value and the second impedance measurement value are based on different measuring cells can thus be taken into account. The first geometry factor and the second geometry factor can be calculated before determining the value indicating the impedance of the suspension.It is also possible for the first and second geometry factors to be determined experimentally in a calibration phase prior to the actual implementation of the method. The first and second geometry factors can be assumed to be constant for determining several values ​​indicative of the suspension's impedance during impedance spectroscopy.

[0013] According to the invention, the value indicating the impedance of the suspension is determined according to the following formula: Z = k 1 λ 1 − λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 2 , where Z sig | 1 denotes the first impedance measured value, Z sig | 2 denotes the second impedance measured value, G el -1< denotes a correction function that maps the transfer behavior of the measuring arrangement, λ 1 denotes a first geometry factor that maps the measurement geometry of the first pair of measuring electrodes, λ 2 denotes a second geometry factor that maps the measurement geometry of the second pair of measuring electrodes, and k denotes a proportionality constant. The first geometry factor λ 1 and the second geometry factor λ 2 can map the geometry of the different measuring cells described above. The correction function G el -1< is denoted as an inverse function, which is indicated by the superscript -1. This notation takes into account the fact that Z sig | 1 and Z sig | 2 are the impedance measured values ​​after passing through the measuring arrangement.The transfer behavior of the measurement setup can be described by a function G el . Thus, the correction function G el -1< allows for recalculating which impedance measurements were directly applied to the measuring electrodes. The values ​​to be used for k, G el -1< , λ 1 , and λ 2 can be calculated or determined in a calibration phase, or partially calculated and partially determined in a calibration phase.

[0014] According to a further embodiment, the method comprises measuring the first voltage at the first pair of measuring electrodes, and measuring the second voltage at the second pair of measuring electrodes, wherein the measurement of the first voltage and the measurement of the second voltage occur substantially simultaneously. In this way, it is possible to minimize or completely eliminate the influence of the temporal variability of the interference on the determination of the value indicating the impedance of a suspension.

[0015] According to an alternative embodiment, the method comprises: measuring the first voltage at the first pair of measuring electrodes, and measuring the second voltage at the second pair of measuring electrodes, wherein the measuring of the first voltage and the measuring of the second voltage occur at different times. In particular, the voltage measured at the first pair of measuring electrodes and the voltage measured at the second pair of measuring electrodes can be provided one after the other to the downstream signal processing. For this purpose, for example, corresponding switches can be provided between the first pair of measuring electrodes and the second pair of measuring electrodes and the downstream signal processing. In this way, the downstream signal processing can be implemented with comparatively few components and can be designed to be compact and energy-efficient.

[0016] Regardless of whether the measurement of the first voltage and the measurement of the second voltage occur essentially simultaneously or at different times, the measurement of the first voltage and the measurement of the second voltage each take place when the excitation current oscillating at the excitation frequency is generated by the suspension. In other words, voltage is measured at the measuring electrodes while the excitation current oscillating at the excitation frequency is applied to the suspension. Accordingly, the electrical behavior of the suspension is measured when the excitation current oscillating at the excitation frequency is applied. The excitation current can also be measured. It is also possible that the excitation current is known or assumed to be known as a result of a known generation mechanism.

[0017] According to a further embodiment, the excitation frequency of the excitation current is between 50 kHz and 20 MHz. An excitation current in this frequency range allows particularly relevant values ​​indicative of the impedance of a cell population to be determined, which are particularly useful for determining the quantities and / or size and / or homogeneity of the living cells in the cell population. This frequency range lies in the so-called β-dispersion region of many cell populations, which will be discussed again below.

[0018] According to a further embodiment, determining the first impedance measurement value and determining the second impedance measurement value comprises sampling the excitation current, sampling the first voltage, and sampling the second voltage. Sampling the excitation current, the first voltage, and the second voltage assists in the highly accurate determination of the value indicative of the impedance of a suspension over a wide frequency range. Sampling the excitation current, the first voltage, and the second voltage enable the generation of samples at precisely defined points in time. These temporally discretized samples can be analyzed and correlated after sampling, without the signal processing downstream of the sampling requiring real-time capability.A comparatively large database, clearly defined in the time dimension by sampling, can be used to determine the value indicating the suspension's impedance with high precision. Compared to previous approaches, which rely on determining characteristic properties of a suspension through complex analog signal processing, sampling allows for the minimization of noise after sampling, as the signal processing of the discretized sampled values ​​can be designed to be very robust. The noise between the measurement of the excitation current, first voltage, and second voltage and the sampling of the excitation current, first voltage, and second voltage can be kept very low.Furthermore, the sampling of the excitation current, the first voltage and the second voltage can be matched to the excitation frequency, which enables high sampling accuracy at the relevant frequencies and spectral limitation of the interference.

[0019] Sampling the excitation current, sampling the first voltage, and sampling the second voltage can be a sampling of derived values ​​of the excitation current, the first voltage, and the second voltage. For example, a first signal can be generated for the excitation current, which represents the excitation current. This first signal can be a voltage signal, for example. The first signal can then be sampled directly or after amplification. Such signal processing also falls under the term "sampling the excitation current" in the sense of this document. It is also possible for the first voltage between the first pair of measuring electrodes to be tapped in the form of a second signal. This second signal can also be sampled either directly or with amplified signal. As with sampling the excitation current, such preprocessing of the second signal also falls under the term "sampling the first voltage."It is also possible for the second voltage between the second pair of measuring electrodes to be tapped in the form of a third signal. This third signal can also be sampled either directly or amplified. As with sampling the excitation current, such preprocessing of the third signal also falls under the term "sampling the second voltage."

[0020] According to a further embodiment, the method further comprises the following steps: setting a first sampling rate for sampling the excitation current, setting a second sampling rate for sampling the first voltage, and setting a third sampling rate for sampling the second voltage. In particular, the setting of the first sampling rate and / or the setting of the second sampling rate and / or the setting of the third sampling rate can be based on the excitation frequency of the excitation current. The first sampling rate, the second sampling rate, and the third sampling rate can be the same or different. Setting the first sampling rate, the setting of the second sampling rate, and the setting of the third sampling rate allow the determination of the value indicating the impedance of the suspension to be adapted to the framework conditions of a current measuring process, in particular to the excitation frequency of the excitation current for the current measuring process.In this way, it is possible to use optimized sampling rates for each measurement process, in particular to set a sampling rate optimized with regard to accuracy and / or signal processing complexity. The first sampling rate, the second sampling rate, and the third sampling rate are used for sampling the excitation current, for sampling the first voltage, and for sampling the second voltage, respectively. Accordingly, the first sampling rate, the second sampling rate, and the third sampling rate are set before sampling the excitation current, the first voltage, and the second voltage. The formulation of setting the first sampling rate, setting the second sampling rate, and setting the third sampling rate also includes setting a sampling rate and using this one sampling rate as the first sampling rate, as the second sampling rate, and as the third sampling rate.

[0021] According to a further embodiment, the first sampling rate, the second sampling rate, and the third sampling rate are set to at least 4 times the excitation frequency of the excitation current, in particular substantially 4 times the excitation frequency of the excitation current. By using at least 4 times the excitation frequency of the excitation current for sampling the excitation current, the first voltage, and the second voltage, it is ensured that the excitation current, the first voltage, and the second voltage are sampled very precisely and that no signal information is lost around the excitation frequency. The sampling theorem is exceeded by a reassuring margin. In particular, the first sampling rate, the second sampling rate, and the third sampling rate can be set substantially 4 times the excitation frequency of the excitation current, or even exactly 4 times the excitation frequency of the excitation current.

[0022] According to a further embodiment, the step of determining the first impedance measured value comprises carrying out a first complex Fourier transform on the basis of the sample values ​​of the excitation current and the sample values ​​of the first voltage, and the step of determining the second impedance measured value comprises carrying out a second complex Fourier transform on the basis of the sample values ​​of the excitation current and the sample values ​​of the second voltage. In particular, a complex discrete Fourier transform can be used here. The sample values ​​of the excitation current, the sample values ​​of the first voltage, and the sample values ​​of the second voltage can be viewed as respective real parts of a complex current or voltage signal. By means of a complex Fourier transform, which takes sampled current and voltage values ​​into account together, the complex impedance between the excitation current and the first voltage orbetween the excitation current and the second voltage can be determined. In particular, complex impedances at the excitation frequency can be determined, which can form the basis for the first impedance measurement value or the second impedance measurement value.

[0023] According to a further embodiment, the method further comprises: determining a third impedance measurement value based on the excitation current and a third voltage at a third pair of measuring electrodes; determining the value indicative of the impedance of the suspension by relating the first impedance measurement value, the second impedance measurement value, and the third impedance measurement value. By determining a third impedance measurement value and relating the first, second, and third impedance measurement values, interference can be removed from the measurement results to an even greater extent. In particular, by using three impedance measurement values ​​from three different pairs of measuring electrodes, interference of an order of magnitude higher can be reduced or even eliminated than is possible with the use of two different pairs of measuring electrodes.The three pairs of measuring electrodes form three different geometric arrangements in the suspension. Thus, measurement values ​​are available for three measuring cells. The three pairs of measuring electrodes can be formed by a total of four or more measuring electrodes. In particular, it is possible to use a total of four, five, or six measuring electrodes, of which three different pairs are used to determine an impedance measurement value.

[0024] According to a further embodiment, determining the value indicating the impedance of the suspension comprises a first subtraction of the first impedance measurement value and the second impedance measurement value, a second subtraction of the first impedance measurement value and the third impedance measurement value, and a third subtraction of the second impedance measurement value and the third impedance measurement value. Analogous to the above-described case of two pairs of measuring electrodes, the first, second, and third subtractions represent simple but effective measures for eliminating a significant portion of the interference from the measured values.

[0025] According to an alternative embodiment, determining the value indicating the impedance of the suspension comprises a first subtraction of a first adjusted impedance value and a second adjusted impedance value, a second subtraction of the first adjusted impedance value and a third adjusted impedance value, and a third subtraction of the second adjusted impedance value and the third adjusted impedance value, wherein the first adjusted impedance value, the second adjusted impedance value, and the third adjusted impedance value are obtained by applying a correction function to the first impedance measurement value, the second impedance measurement value, and the third impedance measurement value. According to a further embodiment, the correction function can map the transfer behavior of the measuring arrangement.

[0026] According to a further embodiment, determining the value indicating the impedance of the suspension comprises a first subtraction of a first geometry factor and a second geometry factor, a second subtraction of the first geometry factor and a third geometry factor, and a third subtraction of the second geometry factor and the third geometry factor, wherein the first geometry factor represents the measurement geometry of the first pair of measuring electrodes, the second geometry factor represents the measurement geometry of the second pair of measuring electrodes, and the third geometry factor represents the measurement geometry of the third pair of measuring electrodes. By said subtractions, the different geometric arrangements of the three pairs of measuring electrodes can be taken into account in a simple but effective manner.

[0027] According to a further embodiment, the value indicating the impedance of the suspension is determined according to the following formula: Z 2 = k 2 λ 3 G el − 1 Z sig 2 − G el − 1 Z sig 1 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 + + k 2 λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 3 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 + + k 2 λ 1 G el − 1 Z sig 3 − G el − 1 Z sig 2 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 , where Z sig | 1 denotes the first impedance measurement value, Z sig | 2 denotes the second impedance measurement value, Z sig | 3 denotes the third impedance measurement value, G el -1< denotes a correction function that maps the transfer behavior of the measuring arrangement, λ 1 denotes a first geometry factor that maps the measurement geometry of the first pair of measuring electrodes, λ 2 denotes a second geometry factor that maps the measurement geometry of the second pair of measuring electrodes, λ 3 denotes a third geometry factor that maps the measurement geometry of the third pair of measuring electrodes, and k 2 denotes a proportionality constant. The values ​​to be used for k 2 , G el -1< , λ 1 , λ 2 and λ 3 can be calculated or determined in a calibration phase or partially calculated and partially determined in a calibration phase.

[0028] According to a further embodiment, the value indicating the impedance of the suspension is determined according to the following formula: Z = k 2 λ 3 G el − 1 Z sig 2 − G el − 1 Z sig 1 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 + + k 2 λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 3 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 + + k 2 λ 1 G el − 1 Z sig 3 − G el − 1 Z sig 2 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 , where Z sig | 1 denotes the first impedance measurement value, Z sig | 2 denotes the second impedance measurement value, Z sig | 3 denotes the third impedance measurement value, G el -1< denotes a correction function that maps the transfer behavior of the measuring arrangement, λ 2 denotes a first geometry factor that maps the measurement geometry of the first pair of measuring electrodes, λ 2 denotes a second geometry factor that maps the measurement geometry of the second pair of measuring electrodes, λ 3 denotes a third geometry factor that maps the measurement geometry of the third pair of measuring electrodes, and k 2 denotes a proportionality constant. The values ​​to be used for k 2 , G el -1< , λ 1 , λ 2 and λ 3 can be calculated or determined in a calibration phase or partially calculated and partially determined in a calibration phase.

[0029] Alternatively, the invention comprises a method for determining a value indicative of the impedance of a suspension within the framework of impedance spectroscopy, comprising the following steps: generating an excitation voltage oscillating at an excitation frequency and applied to the suspension; determining a first impedance measurement value based on the excitation voltage and a first current through a first pair of measuring electrodes; determining a second impedance measurement value based on the excitation voltage and a second current through a second pair of measuring electrodes; determining the value indicative of the impedance of the suspension by relating the first impedance measurement value and the second impedance measurement value.Generating an excitation voltage and determining first and second impedance measurement values ​​based on the excitation voltage and the first and second currents represents an alternative embodiment to the above-described generation of an excitation current and determining first and second impedance measurement values ​​based on the excitation current and the first and second voltages. In other words, alternative embodiments of the invention involve applying an excitation voltage to the suspension and using current flows through measuring electrodes to determine the impedance measurement values. For example, it is possible to apply the excitation voltage such that no current flows through a pair of excitation electrodes. In other words, the pair of excitation electrodes can merely be used to provide a time-varying potential difference in the suspension.Furthermore, the first pair of measuring electrodes and the second pair of measuring electrodes can each be connected to each other, for example, via a measuring resistor or a measuring capacitor. Thus, a closed alternating current circuit is present through the measuring resistor / measuring capacitor and the suspension, and the voltage across the measuring resistor / measuring capacitor can be tapped as a measure of the current through the respective pair of measuring electrodes. The additional features, modifications, and technical effects described above with reference to the method using an excitation current apply analogously to the method using an excitation voltage and are hereby explicitly disclosed for this alternative solution.

[0030] Exemplary embodiments of the invention further comprise a method for deriving at least one characteristic property of a suspension, comprising the following steps: repeatedly performing the method for determining a value indicative of the impedance of a suspension according to one of the embodiments described above, wherein, in the repeated performance of the method, a plurality of different excitation frequencies are used and a plurality of values ​​indicative of the impedance of the suspension are determined for the plurality of different excitation frequencies; deriving a plurality of values ​​indicative of the permittivity of the suspension based on the plurality of values ​​indicative of the impedance of the suspension; and deriving the at least one characteristic property of the suspension by relating the plurality of values ​​indicative of the permittivity of the suspension.In this case, the correlation can include forming a difference between two values ​​indicating the permittivity of the suspension and / or determining the slope of a curve drawn through the plurality of values ​​indicating the permittivity of the suspension, and / or determining an inflection point of a curve drawn through the plurality of values ​​indicating the permittivity of the suspension, and / or determining further characteristic properties of the plurality of values ​​indicating the permittivity of the suspension. These characteristic properties of the set of values ​​obtained can be used to infer characteristic properties of the suspension, in particular characteristic properties of a cell population.By determining the majority of values ​​indicating the permittivity of the suspension with high precision over a comparatively wide frequency range, the characteristic properties of the suspension can also be determined with high accuracy. The majority of the values ​​indicating the permittivity of the suspension can be capacitance values ​​or permittivity values.

[0031] According to a further embodiment, the said method for determining a value indicative of the impedance of a suspension is carried out for between 2 and 50 different excitation frequencies. In particular, the method for determining a value indicative of the impedance of a suspension can be carried out for between 10 and 40 different excitation frequencies, more particularly for between 20 and 30 different excitation frequencies. It has been shown that for the said number of runs of the method and the corresponding number of values ​​indicative of the impedance of the suspension, in particular for between 10 and 40 different excitation frequencies orFurthermore, particularly with between 20 and 30 different excitation frequencies, a good compromise can be achieved between the complexity of the method for deriving at least one characteristic property of the suspension and the accuracy of the results regarding the at least one characteristic property of the suspension. In particular, for between 10 and 40 different excitation frequencies, or further particularly for between 20 and 30 different excitation frequencies, particularly meaningful curves of the values ​​indicating the permittivity of the suspension, in particular the permittivity itself, can be created. The aforementioned number of values ​​allows the creation of curves versus the excitation frequency with sufficient accuracy to determine characteristic properties such as gradient and inflection point with high precision.These statements apply in particular to the derivation of at least one characteristic property of a cell population.

[0032] According to a further embodiment, the different excitation frequencies originate from a frequency range of 100 kHz to 10 MHz. The expression that the different excitation frequencies originate from the mentioned frequency range means that at least the mentioned frequency range is covered by the different excitation frequencies. This in turn means that the lowest excitation frequency is 100 kHz or less and that the highest excitation frequency is 10 MHz or more. In other words, the lowest excitation frequency and the highest excitation frequency form an intermediate excitation frequency range that includes at least the range between 100 kHz and 10 MHz.Using the values ​​indicating the impedance of the suspension for the excitation frequencies from 100 kHz to 10 MHz, one or more characteristic properties of a large number of suspensions, in particular of a large number of cell populations, can be determined with high accuracy.

[0033] In a further embodiment, the different excitation frequencies originate from a frequency range of 50 kHz to 20 MHz. This allows the derivation of the at least one characteristic property of the suspension to be further refined. This applies in particular to the derivation of the at least one characteristic property of a cell population. Due to the increased measurement accuracy and / or the increased reliability of the measurement results, exemplary embodiments of the method described above for determining a value indicative of the impedance of a suspension allow an extension of the frequency range of impedance spectroscopy and thus a more comprehensive determination of one or more characteristic properties of the suspension without having to resort to additional and more complex methods.It is also possible that the method can be applied to an extended range of suspensions, in particular to an extended range of cell populations.

[0034] According to a further embodiment, deriving the at least one characteristic property of the suspension involves creating a curve of the values ​​indicating the permittivity of the suspension over the different excitation frequencies. In other words, a curve can be plotted through the values ​​indicating the permittivity of the suspension versus the excitation frequency. A so-called Cole-Cole fitting can be applied. Characteristics such as differences between end values, gradients, and inflection points can then be determined from the resulting curve or from the resulting curve. The values ​​indicating the permittivity of the suspension can be the determined values ​​directly or calibrated versions of the determined values.

[0035] According to a further embodiment, the suspension is a cell population. In a further embodiment, the at least one characteristic property of the cell population comprises at least one property of the number of living cells, the size of the cells, and the homogeneity of the cells.

[0036] The present invention further comprises a sensor for determining a value indicative of the impedance of a suspension, comprising: an oscillator circuit; a pair of excitation electrodes coupled to the oscillator circuit, wherein an excitation current oscillating at an excitation frequency can be generated through the suspension by means of the oscillator circuit via the pair of excitation electrodes; at least three measuring electrodes for measuring a first voltage in the suspension between a first pair of the at least three measuring electrodes and a second voltage in the suspension between a second pair of the at least three measuring electrodes;and a data processing device configured to determine a first impedance measurement value based on the excitation current and the first voltage, to determine a second impedance measurement value based on the excitation current and the second voltage, and to determine the value indicative of the impedance of the suspension by relating the first impedance measurement value and the second impedance measurement value. The additional features, modifications, and technical effects described above with respect to the method for determining a value indicative of the impedance of a suspension apply analogously to the sensor for determining a value indicative of the impedance of a suspension.

[0037] According to a further embodiment, the at least three measuring electrodes are arranged between the pair of excitation electrodes. In this way, the excitation current is applied at a high intensity along the measuring electrodes, and the ratio of useful signal to interference is high compared to other geometric arrangements. Furthermore, such an arrangement enables a compact sensor design.

[0038] According to a further embodiment, the first pair of the at least three measuring electrodes consists of a first measuring electrode and a second measuring electrode and the second pair of the at least three measuring electrodes consists of the first measuring electrode and a third measuring electrode.

[0039] According to an alternative embodiment, the at least three measuring electrodes are at least four measuring electrodes, wherein the first pair of the at least four measuring electrodes consists of a first measuring electrode and a second measuring electrode and wherein the second pair of the at least four measuring electrodes consists of a third measuring electrode and a fourth measuring electrode.

[0040] The statements made above with reference to the method for determining a value indicative of the impedance of a suspension regarding the different numbers of measuring electrodes apply analogously to the sensor for determining a value indicative of the impedance of a suspension.

[0041] According to a further embodiment, the third and fourth measuring electrodes are arranged between the first and second measuring electrodes. Such an arrangement enables a strong overlap of the measuring cells. This creates a high probability that interference will affect both measuring cells in a very similar or identical manner. This, in turn, allows for the best possible removal of interference from the measured values ​​by relating the first impedance measured value and the second impedance measured value, as discussed in detail above. Furthermore, such an arrangement enables a compact sensor design.

[0042] According to a further embodiment, the third and fourth measuring electrodes are arranged on a different side of the sensor than the first and second measuring electrodes. In this way, the mutual influence of the measuring electrodes can be minimized. A largely independent determination of the first impedance measured value and the second impedance measured value is thus possible. Depending on the general conditions, i.e., depending on the suspension being tested and the existing interference, particularly good measurement results can be achieved in individual cases.

[0043] According to a further embodiment, the data processing device is configured to determine the value indicating the impedance of the suspension by forming a difference between the first impedance measured value and the second impedance measured value.

[0044] According to an alternative embodiment, the data processing device is configured to determine the value indicating the impedance of the suspension by calculating the difference between a first adjusted impedance value and a second adjusted impedance value. The data processing device is configured to obtain the first adjusted impedance value and the second adjusted impedance value by applying a correction function to the first impedance measurement value and the second impedance measurement value. In a further embodiment, the correction function maps the transmission behavior of the measuring arrangement.

[0045] According to a further embodiment, the data processing device is configured to determine the value indicating the impedance of the suspension by means of a difference formation of a first geometry factor and a second geometry factor, wherein the first geometry factor maps the measuring geometry of the first pair of the at least three measuring electrodes and wherein the second geometry factor maps the measuring geometry of the second pair of the at least three measuring electrodes.

[0046] According to a further embodiment, the data processing device is configured to determine the value indicating the impedance of the suspension according to the following formula: Z = k 1 λ 1 − λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 2 , where Z sig | 1 denotes the first impedance measured value, Z sig | 2 denotes the second impedance measured value, G el -1< denotes a correction function that maps the transfer behavior of the measuring arrangement, λ 1 denotes a first geometry factor that maps the measuring geometry of the first pair of the at least three measuring electrodes, λ 2 denotes a second geometry factor that maps the measuring geometry of the second pair of the at least three measuring electrodes, and k denotes a proportionality constant.

[0047] According to a further embodiment, the oscillator circuit is configured to set the excitation frequency in a frequency range from 100 kHz to 10 MHz. This means that the oscillator circuit is capable of setting the excitation frequency in a frequency range from 100 kHz to 10 MHz. This formulation does not preclude the oscillator circuit from being able to set the excitation frequency beyond the specified frequency range. Rather, the formulation means that the oscillator circuit is capable of setting the excitation frequency at least in the frequency range from 100 kHz to 10 MHz. In particular, the oscillator circuit can be configured to set the excitation frequency at least in a frequency range from 50 kHz to 20 MHz.

[0048] According to a further embodiment, the sensor further comprises: a first sampling circuit coupled to at least one of the pair of excitation electrodes and, during operation, providing sample values ​​for the excitation current; and at least one further sampling circuit coupled to the at least three measuring electrodes and, during operation, providing sample values ​​for the first voltage and the second voltage; wherein the data processing device is coupled to the first sampling circuit and the at least one further sampling circuit. To acquire data for the first impedance measurement value and for the second impedance measurement value, respectively, the first sampling circuit and the required further sampling circuit operate simultaneously, i.e., they generate the sample values ​​for the excitation current and the sample values ​​for the first voltage and for the second voltage, respectively, in the same period of time.Furthermore, the first sampling circuit and the required further sampling circuit operate when the excitation current is applied, ie the first sampling circuit and the required further sampling circuit operate in the same period as the oscillator circuit.

[0049] The term "coupled" is used herein to indicate that a signal or electrical quantity can be transmitted from one entity to another, meaning that some type of connection exists between the entities. However, other components, such as amplifiers, transformers, or other electrical components, may be interposed.

[0050] The first sensing circuit can be coupled either to the first excitation electrode or to the second excitation electrode. It can also be coupled to both excitation electrodes. In general, the first sensing circuit can be coupled to one or both excitation electrodes in any suitable manner to enable measurement of the excitation current.

[0051] According to a further embodiment, the first sampling circuit and the at least one further sampling circuit are synchronized with respect to their sampling times.

[0052] According to a further embodiment, the first sampling circuit and the at least one further sampling circuit are coupled to the data processing device via a data memory, wherein the data memory in particular has a data acquisition rate of at least 1 Gbit / s. The data acquisition rate of at least 1 Gbit / s describes a possible data acquisition rate of at least 1 Gbit / s. The data does not have to be acquired by the data memory at this speed. Since the sampling frequency can depend on the excitation frequency, different data acquisition rates can result at the data memory during operation for different excitation frequencies.

[0053] According to a further embodiment, the data processing device is configured to determine the first impedance measured value by means of a first complex Fourier transformation on the basis of the sample values ​​of the excitation current and the sample values ​​of the first voltage, and to determine the second impedance measured value by means of a second complex Fourier transformation on the basis of the sample values ​​of the excitation current and the sample values ​​of the second voltage.

[0054] According to a further embodiment, the first sampling circuit is coupled to the at least one of the pair of excitation electrodes via a first amplifier circuit and the at least one further sampling circuit is coupled to the at least three measuring electrodes via at least one further amplifier circuit.

[0055] According to a further embodiment, a measuring element, in particular a measuring resistor, is coupled to at least one of the pair of excitation electrodes, and the first sampling circuit is configured to provide the sample values ​​for the excitation current based on the voltage drop across the measuring element. For reasons of symmetry, both excitation electrodes can each be coupled to a measuring element, in particular to a measuring resistor, even if the first sampling circuit is only coupled to one of the measuring elements.

[0056] According to a further embodiment, the oscillator circuit is coupled to the pair of excitation electrodes via a transformer. This allows for galvanic decoupling between the oscillator circuit and the excitation electrodes.

[0057] According to a further embodiment, the transformer has a parallel capacitance of 0.5 pF to 10 pF, in particular a parallel capacitance of 1 pF to 5 pF. The parallel capacitance can be a discrete component, such as a capacitor arranged in parallel with the transformer. However, it is also possible for the parallel capacitance to be a parasitic capacitance of the transformer, wherein the transformer is designed such that the parallel capacitance lies within the specified value range. The term parallel capacitance refers to a coupling capacitance between the primary side and the secondary side of the transformer. With a parallel capacitance, the influence of disruptive coupling capacitances, such as those that may exist between the electrodes and the wall of a container for the suspension or between the electrodes and other existing sensors, can be kept to a minimum.Since in the presence of the capacitance parallel to the transformer and other coupling capacitances, the smaller capacitance is often decisive, the influence of an undesirable disturbing coupling capacitance on the size of the parallel capacitance can be reduced.

[0058] According to a further embodiment, the sensor further comprises a control unit coupled to the oscillator circuit, which, during operation, causes the oscillator circuit to successively generate oscillating excitation currents through the suspension at different excitation frequencies. Thus, the control unit can initiate various measurement runs, by means of which impedance spectroscopy can be performed on the suspension. Furthermore, the control unit can be coupled to the first sampling circuit and the at least one further sampling circuit and configured to transmit the currently generated excitation frequency to the first and the at least one further sampling circuit. The first sampling circuit and the at least one further sampling circuit can adjust the sampling rate accordingly. The control unit can also be configured to transmit the currently generated excitation frequency to the data processing device.

[0059] The present invention further comprises a sensor for determining a value indicative of the impedance of a suspension, comprising: an oscillator circuit; a pair of excitation electrodes coupled to the oscillator circuit, wherein an oscillating voltage oscillating at an excitation frequency is generated via the pair of excitation electrodes by means of the oscillator circuit.an excitation voltage applied to the suspension can be generated; at least three measuring electrodes for measuring a first current in the suspension between a first pair of the at least three measuring electrodes and a second current in the suspension between a second pair of the at least three measuring electrodes; and a data processing device configured to determine a first impedance measured value based on the excitation voltage and the first current, to determine a second impedance measured value based on the excitation voltage and the second current, and to determine the value indicative of the impedance of the suspension by relating the first impedance measured value and the second impedance measured value.The additional features, modifications, and technical effects described above with reference to the sensor whose excitation electrodes can generate an excitation current apply analogously to the sensor whose excitation electrodes can generate an excitation voltage and are hereby explicitly disclosed for this alternative solution. Furthermore, the above considerations for the method using an excitation voltage are analogously applicable to the sensor whose excitation electrodes can generate an excitation voltage.

[0060] Exemplary embodiments of the invention further comprise a computer program or a computer program product containing program instructions that, when executed on a data processing system, perform a method according to one of the embodiments described above. The individual steps of the method can be initiated by the program instructions and executed by other components or executed in the data processing system itself.

[0061] Further exemplary embodiments of the invention are described below with reference to the accompanying figures. Fig. 1 shows a sensor for determining a value indicative of the impedance of a suspension according to an exemplary embodiment of the invention in a side view; Fig. 2 shows a sensor according to an exemplary embodiment of the invention, partly shown as a block diagram and partly shown as a circuit diagram; Fig. 3 shows one opposite Fig. 2 modified sensor according to another exemplary embodiment of the invention, partly shown as a block diagram and partly shown as a circuit diagram; Fig. 4 shows a sensor for determining a value indicative of the impedance of a suspension according to another exemplary embodiment of the invention in a perspective view; Fig. 5 shows a sensor for determining a value indicative of the impedance of a suspension according to another exemplary embodiment of the invention in a side view; Fig. 6 shows a sensor according to an exemplary embodiment of the invention, partly shown as a block diagram and partly shown as a circuit diagram; Fig. 7 shows one opposite Fig. 6 modified sensor according to another exemplary embodiment of the invention, partly shown as a block diagram and partly shown as a circuit diagram; Fig. 8 shows a sensor for determining a value indicating the impedance of a suspension according to another exemplary embodiment of the invention in a side view; and Fig. 9 shows an example of a curve of permittivity values ​​versus the excitation frequency and illustrates the derivation of characteristic properties of the suspension.

[0062] Fig. 1 shows a sensor 2 according to an exemplary embodiment of the invention in a side view. The sensor 2 is designed to determine a value indicating the impedance of a suspension. The sensor 2 is designed to be immersed in the suspension to be analyzed, in particular for immersion in a cell population to be analyzed. For this purpose, the sensor 2 has a rod-shaped sensor body 4, which Fig. 1 is shown cut off. The rod-shaped sensor body 4 can also be described as substantially cylindrical. The rod-shaped sensor body 4 can have a suitable length so that the analysis of the suspension can take place at a desired location in a container or reactor containing the suspension.

[0063] The rod-shaped sensor body 4 has six electrodes. In particular, the rod-shaped sensor body 4 has a pair of excitation electrodes, namely a first excitation electrode 8 and a second excitation electrode 10, a first pair of measuring electrodes, namely a first measuring electrode 11 and a second measuring electrode 12, and a second pair of measuring electrodes, namely a third measuring electrode 13 and a fourth measuring electrode 14. In the exemplary embodiment of Fig. 1 The six electrodes 8, 10, 11, 12, 13, and 14 are annular, i.e., they are formed circumferentially around the rod-shaped sensor body 4. It is emphasized that the six electrodes can also be present in other geometric configurations, e.g., in an elongated form along the rod-shaped sensor body 4.

[0064] In the exemplary embodiment of Fig. 1 The six electrodes 8, 10, 11, 12, 13, and 14 are arranged in an end region of the rod-shaped sensor body 4. However, they can also be arranged in any other suitable region of the rod-shaped sensor body 4 or the sensor 2.

[0065] In the exemplary embodiment of Fig. 1 The first pair of measuring electrodes 11, 12 and the second pair of measuring electrodes 13, 14 are arranged between the excitation electrodes 8, 10. In particular, the first measuring electrode 11 is arranged adjacent to the first excitation electrode 8, and the third measuring electrode 13 is arranged adjacent to the first measuring electrode 11. Further in particular, the second measuring electrode 12 is arranged adjacent to the second excitation electrode 10, and the fourth measuring electrode 14 is arranged adjacent to the second measuring electrode 12. The second pair of measuring electrodes 13, 14 is arranged between the first pair of measuring electrodes 11, 12. The first measuring electrode 11 and the third measuring electrode 13 are closer to the first excitation electrode 8 than an imaginary center line between the first excitation electrode 8 and the second excitation electrode 10.The second measuring electrode 12 and the fourth measuring electrode 14 are closer to the second excitation electrode 10 than an imaginary center line between the first excitation electrode 8 and the second excitation electrode 10. By arranging the measuring electrodes 11, 12, 13, 14 between the excitation electrodes 8, 10 and in the vicinity of the excitation electrodes 8, 10, a comparatively high voltage can be measured when the excitation current is applied.

[0066] During operation, a first voltage U 1 is measured between the first pair of measuring electrodes 11, 12 and a second voltage U 2 is measured between the second pair of measuring electrodes 13, 14. This is shown in Fig. 1 schematically indicated and is described in detail below with reference to Fig. 2 described.

[0067] Fig. 2 shows a sensor 2 according to an exemplary embodiment of the invention, partly in a block diagram and partly in a circuit diagram. The components of the sensor 2 of the Fig. 2 can be stored in a sensor in Fig. 1 shown physical form. This means that in the circuitry or signal processing design of the sensor 2 of the Fig. 2 This may be the structure of the electrical components of sensor 2 of the Fig. 1 The components used in Fig. 2 shown to the right of the circular coupling points, can be accommodated in the sensor body 4 or in a component connected thereto.

[0068] Sensor 2 has the above-described first excitation electrode 8, second excitation electrode 10, first measuring electrode 11, second measuring electrode 12, third measuring electrode 13, and fourth measuring electrode 14. The six electrodes 8, 10, 11, 12, 13, and 14 are accessible from the outside, meaning they are in contact with the suspension when sensor 2 is immersed in the suspension for analysis. Furthermore, a temperature sensor 58 is provided, which is located outside the housing of sensor 2.

[0069] The sensor 2 comprises an oscillator circuit 16, a signal acquisition and processing circuit 25, a data memory 36, a data processing device 40, a control unit 56, and a power management unit 38. The individual components and the functionality of these subsystems are described in detail below.

[0070] The oscillator circuit 16 includes an oscillator 18 coupled to an oscillation amplifier 20, which in turn is coupled to a transformer 22. The oscillator 18 is supplied with the desired excitation frequency EF via a control input. The excitation frequency EF is determined by the control unit 56, as described in detail below, and passed to the oscillator 18. The oscillator 18 generates an oscillation at the excitation frequency EF, which is passed to the oscillation amplifier 20. The oscillation amplifier 20 generates an excitation current at the excitation frequency EF through the primary winding of the transformer 22. The excitation current is transferred by induction to the secondary winding of the transformer 22, from where the current is applied to the first and second excitation electrodes 8, 10.One end of the secondary winding is connected to the first excitation electrode 8 via a first resistor 24, and the second end of the secondary winding is connected to the second excitation electrode 10 via a second resistor 26. This results in a closed circuit from the first end of the secondary winding through the first resistor 24, via the first excitation electrode 8, through the suspension to the second excitation electrode 10, and through the second resistor 26 to the second end of the secondary winding. In this way, an excitation current oscillating at the excitation frequency EF is generated through the suspension between the first excitation electrode 8 and the second excitation electrode 10. In the exemplary embodiment of the . Fig. 2 The excitation current is a sinusoidal excitation current oscillating at the excitation frequency EF. Furthermore, the excitation current in the exemplary embodiment of the Fig. 2 an amplitude of 1 Vpp to 2 Vpp.

[0071] The transformer 22 ensures galvanic decoupling between the oscillation amplifier 20 and the first and second excitation electrodes 8, 10. A coupling capacitance can be provided in parallel with the transformer 22. In this case, the transformer 22 can also be said to have a parallel capacitance present between the primary winding and the secondary winding. The parallel capacitance can be a discrete component or a parasitic capacitance of the transformer. By being arranged parallel to the transformer, the parallel capacitance can counteract disruptive influences from other coupling capacitances, such as coupling capacitances between the electrodes and the suspension container and / or coupling capacitances between the electrodes and other sensors present in the suspension. The parallel capacitance can be between 1 pF and 5 pF.

[0072] The excitation current oscillating at the excitation frequency EF between the first excitation electrode 8 and the second excitation electrode 10 generates a first alternating voltage between the first measuring electrode 11 and the second measuring electrode 12, as well as a second alternating voltage between the third measuring electrode 13 and the fourth measuring electrode 14. Both the excitation current and the first voltage between the first pair of measuring electrodes 11, 12, as well as the second voltage between the second pair of measuring electrodes 13, 14, are detected and sampled by the signal acquisition and conditioning circuit 25. At the end of the signal processing in the signal acquisition and conditioning circuit 25, digital signals for the excitation current, the first voltage, and the second voltage are available.

[0073] A first signal, which represents the excitation current, is obtained in the following way. The second resistor 26 acts as a measuring resistor for the excitation current. The voltage across the measuring resistor 26 is tapped by means of two conductors and fed as the first signal to a first amplifier circuit 28. The amplified first signal is fed to the first analog-to-digital converter 32. There, the amplified first signal is converted into a digital signal, i.e. the amplified first signal is sampled and quantized. The resulting first samples are output to the data memory 36. It is obvious that the first resistor 24 is not required for obtaining the first signal. However, for reasons of symmetry, the first resistor 24 is nevertheless provided. Furthermore, it is obvious that a signal representative of the excitation current can also be tapped at the first resistor 24.This means that the first amplifier circuit could also be coupled to the first excitation electrode 8 or the first resistor 24. The first resistor 24 and the second resistor 26 can each have a value of 30 Ω to 50 Ω, for example.

[0074] The voltage between the first measuring electrode 11 and the second measuring electrode 12 forms a second signal, which is fed to a second amplifier circuit 30. There, the second signal is amplified, and the amplified second signal is fed to a second analog-to-digital converter 33. The second analog-to-digital converter 33 generates second sample values, which are time-discrete and quantized, analogously to the first analog-to-digital converter 32. The second sample values ​​are also output to the data memory 36.

[0075] The voltage between the third measuring electrode 13 and the fourth measuring electrode 14 forms a third signal, which is fed to a third amplifier circuit 31. There, the third signal is amplified, and the amplified third signal is fed to a third analog-to-digital converter 34. The third analog-to-digital converter 34 generates third sample values, analogous to the first analog-to-digital converter 32, which are time-discrete and quantized. The third sample values ​​are also output to the data memory 36.

[0076] The first analog-to-digital converter 32, the second analog-to-digital converter 33, and the third analog-to-digital converter 34 also receive information about the excitation frequency EF from the control unit 56. The first analog-to-digital converter 32, the second analog-to-digital converter 33, and the third analog-to-digital converter 34 use 4 times the excitation frequency EF to sample the amplified first signal, the amplified second signal, and the amplified third signal. Thus, the first analog-to-digital converter 32, the second analog-to-digital converter 33, and the third analog-to-digital converter 34 create first, second, and third sample values ​​for the excitation current, the first voltage, and the second voltage at 4 times the excitation frequency EF.

[0077] The first, second, and third sample values ​​output by the first analog-to-digital converter 32, the second analog-to-digital converter 33, and the third analog-to-digital converter 34 are buffered in the data memory 36. The data memory 36 thus represents a repository that stores the first sample values, the second sample values, and the third sample values ​​and can make them available for further data processing independently of real time. Thus, from the data memory 36 onward, there are no longer any real-time requirements for the downstream components. On the contrary, the downstream components can access a database accumulated over a certain period of time in the data memory 36. The data memory 36 can be, for example, a DPRAM or any other suitable type of data memory.

[0078] The data memory 36 is coupled to the data processing device 40 and outputs the first sample values ​​for the excitation current, the second sample values ​​for the first voltage between the first measuring electrode 11 and the second measuring electrode 12 and the third sample values ​​for the second voltage between the third measuring electrode 13 and the fourth measuring electrode 14 to the data processing device 40.

[0079] In the data processing device 40, the first, second, and third sample values ​​are transferred to a Fourier transformation module 42. The Fourier transformation module 42 performs two discrete, complex Fourier transformations on the sample values. In particular, the Fourier transformation module 42 performs a first discrete, complex Fourier transformation on the first sample values ​​for the excitation current and the second sample values ​​for the voltage between the first measuring electrode 11 and the second measuring electrode 12, i.e., on the sample values ​​for the excitation current and the sample values ​​for the first voltage. Further, in particular, the Fourier transformation module 42 performs a second discrete, complex Fourier transformation on the first sample values ​​for the excitation current and the third sample values ​​for the voltage between the third measuring electrode 13 and the fourth measuring electrode 14, i.e.,with the sample values ​​for the excitation current and the sample values ​​for the second voltage.

[0080] The Fourier transforms performed in the Fourier transform module 42 are discrete and complex because the time-discrete sample values ​​for the excitation current and for the respective voltage are analyzed as interdependent quantities. The result of these complex Fourier transforms are the amplitudes of the excitation current and the respective measured voltage for various frequencies, as well as the phase shift α between the excitation current and the respective measured voltage for the various frequencies. It is possible for the Fourier transforms to perform a broad spectral analysis of the sample values ​​and then discard all spectral components except for the spectral components at the excitation frequency EF. However, it is also possible for the Fourier transforms to specifically determine the spectral component of the excitation current and the spectral component of the respective voltage between the respective measuring electrodes at the excitation frequency.In this context, the Goertzel algorithm can also be used to specifically determine the spectral components at the excitation frequency EF.

[0081] The amplitude of the spectral component of the excitation current at the excitation frequency EF and the amplitude of the spectral component of the respective measured voltage at the excitation frequency EF are transferred to an impedance and permittivity determination module 48 via a first data transmission connection 44. The phase shift α between the spectral component of the excitation current at the excitation frequency and the spectral component of the respective measured voltage at the excitation frequency is transferred to the impedance and permittivity determination module 48 via a second data transmission connection 46.

[0082] The impedance and permittivity determination module 48 determines a first impedance measured value Z sig | 1 , a second impedance measured value Z sig | 2 , an impedance value Z, a capacitance value C and the permittivity ε of the suspension at the excitation frequency from the transferred parameters. The first impedance measured value Z sig | 1 results from the amplitude of the excitation current at the excitation frequency EF, the amplitude of the first voltage at the excitation frequency EF and the phase shift α between the excitation current and the first voltage at the excitation frequency EF. The first impedance measured value Z sig | 1 is thus a complex impedance measured value at the excitation frequency EF. The second impedance measured value Z sig | 2 results from the amplitude of the excitation current at the excitation frequency EF, the amplitude of the second voltage at the excitation frequency EF and the phase shift α between the excitation current and the second voltage at the excitation frequency EF.The second impedance measurement value Z sig | 2 is thus a complex impedance measurement value at the excitation frequency EF. As described above, the aforementioned amplitudes of the excitation current, first voltage, and second voltage, as well as the aforementioned phase shifts, are available as results of the first and second complex Fourier transformations. Thus, the first impedance measurement value Z sig | 1 and the second impedance measurement value Z sig | 2 can be conveniently calculated from the data available in the impedance and permittivity determination module 48. It is emphasized that the first impedance measurement value Z sig | 1 and the second impedance measurement value Z sig | 2 can also be determined in another way from the first signal, ie the voltage tapped at the second resistor 26, the second signal, ie the voltage tapped at the first pair of measuring electrodes 11, 12, and the third signal, ie the voltage tapped at the second pair of measuring electrodes 13, 14.The signal processing described in detail above allows for a particularly precise determination of the first impedance measurement value Z sig | 1 and the second impedance measurement value Z sig | 2 . However, for the determination of the impedance value Z described below, the method of determining the first impedance measurement value Z sig | 1 and the second impedance measurement value Z sig | 2 is not crucial. Therefore, any suitable signal processing method can be used.

[0083] The impedance and permittivity determination module 48 determines the impedance value Z according to the following formula: Z = k 1 λ 1 − λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 2 .

[0084] Here, Z sig | 1 denotes the first impedance measurement value and Z sig | 2 denotes the second impedance measurement value, as described above. G el -1< denotes a correction function that reflects the transfer behavior of the measurement setup. In the exemplary embodiment of Fig. 2 G el -1< corrects those artifacts that have been introduced into the signals between the respective electrodes and the associated analog-to-digital converters. These can include, for example, propagation time differences in the individual signal paths, non-linear amplification in the amplifier circuits, etc. Accordingly, G el -1< completely or at least approximately restores those impedance measurement values ​​that were directly applied to the electrodes. Furthermore, λ 1 denotes a first geometry factor that maps the measurement geometry of the first pair of measuring electrodes 11, 12, and λ 2 a second geometry factor that maps the measurement geometry of the second pair of measuring electrodes 13, 14. The first geometry factor λ 1 and the second geometry factor λ 2 describe the respective measuring cells that form the basis of the voltage measurements at the first pair of measuring electrodes 11, 12 and at the second pair of measuring electrodes 13, 14.The nature of the first geometry factor λ 1 and the second geometry factor λ 2 is described in detail below. The variable k denotes a proportionality constant.

[0085] By using the first impedance measured value Z sig | 1 and the second impedance measured value Z sig | 2 and relating the first impedance measured value Z sig | 1 and the second impedance measured value Z sig | 2 according to the above formula, an impedance value Z can be determined that is very robust against interference. In particular, by calculating the difference between the impedance measured values ​​adjusted with the correction function G el -1< and the difference between the geometry factors, it can be achieved that low-order interference in the two measurements cancels each other out. The impedance value Z obtained using the above formula only contains higher-order interference, which is comparatively small in many applications. This allows a high level of measurement accuracy to be achieved.

[0086] The capacitance value C and the permittivity ε are then calculated from the impedance value Z. In this way, the material property permittivity ε of the suspension is derived from the impedance value Z. Known approaches and methods can be used to derive the permittivity ε. By obtaining the impedance value Z with high precision, as described herein, improved results can be achieved compared to previous sensors, even when using known methods for deriving the permittivity ε.

[0087] Thus, the impedance value Z, the capacitance value C and the permittivity ε are available as results of the signal processing in the data processing device 40. In particular, these values ​​are available as results for the excitation of the suspension with a specific excitation frequency. One or more of these values ​​can be output for further processing. The output can be sent to an external unit or, as in the exemplary embodiment of the Fig. 2 shown, to the control unit 56 present in the sensor 2. In the exemplary embodiment of the Fig. 2 the value determined for the permittivity ε is output to the control unit 56.

[0088] The data processing device 40 can be implemented in software or as an arrangement of hardware components. It is also possible for the data processing device 40 to be implemented partly in software and partly in hardware. The same applies to the control unit 56 described below.

[0089] The control unit 56 is connected to the power management unit 38, to the oscillator circuit 16, to the signal acquisition and processing circuit 25, and to the data processing device 40. The control unit 56 controls the method for determining a value indicative of the impedance of a suspension according to exemplary embodiments of the invention. For this purpose, the control unit 56 is configured to set the excitation frequency EF for the method. In particular, the control unit is configured to successively set a plurality of excitation frequencies for a plurality of runs of the method within the framework of impedance spectroscopy.

[0090] For a given run, the control unit 56 transmits the specified excitation frequency EF to the oscillator circuit 16, where the oscillator 18 generates an oscillation at the excitation frequency EF, to the signal acquisition and conditioning circuit 25, where the first analog-to-digital converter 32, the second analog-to-digital converter 33, and the third analog-to-digital converter 34 adjust the sampling rate based on the excitation frequency EF, and to the data processing device 40, where the Fourier transform module 42 analyzes the sample values ​​of excitation current, first voltage, and second voltage with respect to the spectral signal components at the excitation frequency.

[0091] Furthermore, the control unit 56 in the exemplary embodiment of Fig. 2 coupled to the data processing device 40 in such a way that the data processing device 40 transmits the permittivity ε determined for the excitation frequency EF to the control unit 56. The control unit 56 can then determine a new excitation frequency for the next run of the method within the framework of impedance spectroscopy.

[0092] After a plurality of permittivity values ​​for different excitation frequencies have been determined, the control unit 56 can derive one or more characteristic properties of the suspension from the plurality of permittivity values. To do so, the control unit can plot a curve through the plurality of permittivity values ​​and derive the characteristic properties of the suspension from the curve, as described below with reference to Fig. 9 Such a correlation of the plurality of permittivity values ​​can also be performed outside of sensor 2.

[0093] The control unit 56 is coupled to the power management circuit 38 to signal the start and end of a process run. Based on these signals, the power management circuit 38 supplies the oscillation amplifier 20 as well as the first amplifier circuit 28, the second amplifier circuit 30, and the third amplifier circuit 31 with the positive supply voltage V+ and the negative supply voltage V-, which in the present exemplary embodiment are +4.5 V and -4 V, respectively. After the end of a process run, the power management circuit 38 separates the positive and negative supply voltages and transmits a shutdown signal ("Power Down") to the oscillator 18, the first analog-to-digital converter 32, the second analog-to-digital converter 33, the third analog-to-digital converter 34, and the data memory 36.In this way, the sensor can save electrical energy between runs of the process for determining the value indicative of the impedance.

[0094] The power management circuit 38 can obtain the electrical energy from outside the sensor 2 or have an internal energy reservoir, e.g. in the form of a battery.

[0095] To protect the sensor 2, the power management circuit 38 can open the power supply when the temperature sensor 58 measures a temperature above a predetermined threshold.

[0096] Fig. 3 shows a sensor 2 according to a Fig. 2 modified, further exemplary embodiment of the invention, again shown partly in a block diagram and partly in a circuit diagram. In particular, the modification relates to the signal processing in the signal acquisition and conditioning circuit 25. In general, corresponding components are denoted by the same reference numerals as in Fig. 2 For their description, reference is made to the above explanations.

[0097] The signal acquisition and processing circuit 25 of the embodiment of the Fig. 3 has no third amplifier circuit 31 and no third digital-to-analog converter 34. Instead, the second amplifier circuit 30 can be connected selectively to the first pair of measuring electrodes 11, 12 or to the second pair of measuring electrodes 13, 14. For this purpose, a first selection switch 29a and a second selection switch 29b are provided. The first selection switch 29a connects either the first measuring electrode 11 or the third measuring electrode 13 to the second amplifier circuit 30. The second selection switch 29b connects either the second measuring electrode 12 or the fourth measuring electrode 14 to the second amplifier circuit 30. Thus, either the first voltage, i.e. the voltage between the first and second measuring electrodes 11, 12, or the second voltage, i.e. the voltage between the third and fourth measuring electrodes 13, 14, can be passed on to the second analog-to-digital converter 33 via the second amplifier circuit 30.

[0098] For the method of determining the value indicating the impedance of the suspension, the modification of the Fig. 3 that the first impedance measurement value and the second impedance measurement value are determined based on signals that are sampled at different times from one another. However, the method can be implemented with a sensor 2 that has only one further amplifier circuit 30 in addition to the first amplifier circuit 28 and only one further analog-to-digital converter 33 in addition to the first analog-to-digital converter 32.

[0099] Fig. 4 shows a sensor 2 according to a Fig. 1 modified, further exemplary embodiment of the invention in a perspective view. The modification relates to the geometric arrangement of the first and second pair of measuring electrodes. Compared to the embodiment of the Fig. 1 The first measuring electrode 11, the second measuring electrode 12, the third measuring electrode 13, and the fourth measuring electrode 14 are not ring-shaped, but rather partially ring-shaped. Each of the four measuring electrodes extends over a circular sector of slightly less than 180° along the cylindrical outer surface of the rod-shaped sensor body 4. In the view of Fig. 4 The first measuring electrode 11 and the second measuring electrode 12 are arranged on the left side of the sensor body 4, and the third measuring electrode 13 and the fourth measuring electrode 14 are arranged on the right side of the sensor body 4. In other words, the first pair of measuring electrodes 11, 12 and the second pair of measuring electrodes 13, 14 are arranged on different sides of the sensor 2. Such an arrangement allows for minimal mutual influence between the electrode pairs, which could potentially negatively impact the measurement accuracy.

[0100] Fig. 5 shows a sensor 2 according to a Fig. 1 modified, further exemplary embodiment of the invention in a side view. The modification relates to the number and geometric arrangement of the measuring electrodes. The sensor 2 of the exemplary embodiment of the Fig. 5 has three measuring electrodes, a first measuring electrode 11, a second measuring electrode 12 and a third measuring electrode 13. The first measuring electrode 11 and the second measuring electrode 12 correspond in their arrangement to the first pair of measuring electrodes 11, 12 of the embodiment of the Fig. 1 . The third measuring electrode 13 of the embodiment of the Fig. 5 is located where in the embodiment of the Fig. 1 the fourth measuring electrode 14 was arranged.

[0101] In the exemplary embodiment of the Fig. 5 The first pair of measuring electrodes consists of the first measuring electrode 11 and the second measuring electrode 12. The second pair of measuring electrodes consists of the first measuring electrode 11 and the third measuring electrode 13. During operation, a first voltage U 1 is measured at the first pair of measuring electrodes 11, 12, while a second voltage U 2 is measured at the second pair of measuring electrodes 11, 13. In other words, the first measuring electrode 11 forms a potential reference point for both the measurement of the first voltage and the measurement of the second voltage. Two exemplary embodiments of the downstream signal processing of the sensor 2 of the Fig. 5 are discussed below with reference to the Fig. 6 and 7 described.

[0102] Fig. 6 shows a sensor 2 according to another exemplary embodiment of the invention, partly shown in a block diagram and partly in a circuit diagram. The components of the sensor 2 of the Fig. 6 can be stored in a sensor in Fig. 5 shown physical form. This means that in the circuitry or signal processing design of the sensor 2 of the Fig. 6 This may be the structure of the electrical components of sensor 2 of the Fig. 5 act. Thus, Fig. 6 to Fig. 5 as well as Fig. 2 to Fig. 1 . The sensor 2 of the Fig. 6 is overall very similar and largely identical to the Sensor 2 of the Fig. 2 . Corresponding components are marked with corresponding reference symbols. For the description of the components, please refer to the description of the Fig. 2 referred to above.

[0103] The changes in the design of the Fig. 6 compared to the design of the Fig. 2 take into account the fact that sensor 2 of the Fig. 6 has only three measuring electrodes 11, 12 and 13, as described above with reference to Fig. 5 The first measuring electrode 11 can be selectively connected to the second amplifier circuit 30 or the third amplifier circuit 31 by means of a selection switch 29c. The second measuring electrode 12 is connected to the second amplifier circuit 30, and the third measuring electrode 13 is connected to the third amplifier circuit 31. Thus, either the first voltage can be passed on to the second analog-to-digital converter 33 via the second amplifier circuit 30, or the second voltage can be passed on to the third analog-to-digital converter 34 via the third amplifier circuit 31. For the method for determining the value indicating the impedance of the suspension, this means that the first impedance measured value and the second impedance measured value are determined on the basis of signals that are tapped at different times from one another.

[0104] Fig. 7 shows a sensor 2 according to a Fig. 6 modified, further exemplary embodiment of the invention, again shown partly in a block diagram and partly in a circuit diagram. In particular, the modification relates to the signal processing in the signal acquisition and conditioning circuit 25. In general, corresponding components are denoted by the same reference numerals as in Fig. 6 For their description, reference is made to the above explanations.

[0105] The signal acquisition and processing circuit 25 of the embodiment of the Fig. 7 has no third amplifier circuit 31 and no third digital-to-analog converter 34. Instead, the second amplifier circuit 30 is permanently connected to the first measuring electrode 11 and can be optionally connected to the second measuring electrode 12 or the third measuring electrode 13. A selection switch 29d is provided for this purpose. Thus, via the second amplifier circuit 30, either the first voltage, i.e. the voltage between the first and second measuring electrodes 11, 12, or the second voltage, i.e. the voltage between the first and third measuring electrodes 11, 13, can be passed on to the second analog-to-digital converter 33. For the method for determining the value indicating the impedance of the suspension, this means that the first impedance measured value and the second impedance measured value are determined on the basis of signals that are tapped at different times from one another.

[0106] Fig. 8 shows a sensor 2 according to another exemplary embodiment of the invention in a side view. The sensor 2 of the Fig. 8 has, like sensor 2 of the Fig. 1 , a first excitation electrode 8, a second excitation electrode 10, a first measuring electrode 11, a second measuring electrode 12, a third measuring electrode 13 and a fourth measuring electrode 14. The six electrodes are in the sensor 2 of the Fig. 8 arranged in the same way as in the sensor 2 of the Fig. 1 However, the four measuring electrodes 11, 12, 13, 14 of the sensor 2 of the Fig. 8 three pairs of measuring electrodes. In particular, a first pair of measuring electrodes consists of der ersten Measuring electrode 11 and the second measuring electrode 12. A second pair of measuring electrodes consists of the first measuring electrode 11 and the fourth measuring electrode 14. A third pair of measuring electrodes consists of the third measuring electrode 13 and the fourth measuring electrode 14.

[0107] During operation, a first voltage U is measured at the first pair of measuring electrodes 11 and 12, a second voltage U 2 is measured at the second pair of measuring electrodes 11 and 14, and a third voltage U 3 is measured at the third pair of measuring electrodes 13 and 14. Based on the excitation current, the first voltage U 1 , the second voltage U 2 and the third voltage U 3, a first impedance measurement value, a second impedance measurement value, and a third impedance measurement value are determined. These three impedance measurements are related to one another to determine an impedance value for the suspension. By using three pairs of measuring electrodes, which are made up of a total of four measuring electrodes, interference can be eliminated particularly well and a particularly precise impedance value for the suspension can be determined.

[0108] The impedance value Z can be determined according to the following formula: Z 2 = k 2 λ 3 G el − 1 Z sig 2 − G el − 1 Z sig 1 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 + + k 2 λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 3 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 + + k 2 λ 1 G el − 1 Z sig 3 − G el − 1 Z sig 2 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 .

[0109] Here, Z sig | 1 denotes the first impedance measurement value, Z sig | 2 the second impedance measurement value, and Z sig | 3 the third impedance measurement value. G el -1< denotes a correction function that maps the transfer behavior of the measuring arrangement, as described above. Furthermore, λ 1 denotes a first geometry factor that maps the measurement geometry of the first pair of measuring electrodes 11, 12, λ 2 a second geometry factor that maps the measurement geometry of the second pair of measuring electrodes 11, 14, and λ 3 a third geometry factor that maps the measurement geometry of the third pair of measuring electrodes 13, 14. The variable k 2 denotes a proportionality constant.

[0110] The above-mentioned Fig. 2 , 3 , 6 and 7 The statements made regarding simultaneous or time-shifted signal processing apply to sensor 2 of the Fig. 8 Analog. For example, the four measuring electrodes can be coupled to two amplifier circuits and two analog-to-digital converters, so that partially simultaneous and partially time-shifted signal processing takes place for the three measuring voltages. For example, the first voltage U 1 and the third voltage U 3 can be measured essentially simultaneously, while the second voltage U 2 is measured afterwards. It is also possible, for example, for the four measuring electrodes to be coupled to a single amplifier circuit and a single analog-to-digital converter by means of suitable selection switches, and for the three voltages to be measured sequentially.

[0111] It is further emphasized that more than four measuring electrodes can be present and that more than three pairs of measuring electrodes can be formed. More than three impedance measurements can also be correlated to determine the value indicating the impedance of the suspension.

[0112] Two formulas are given above that can be used to determine a value indicative of the suspension's impedance for the case of two impedance measurements and for the case of three impedance measurements. Some aids to understanding the formulas are provided below.

[0113] As described above, the aim of the method is to determine a value indicating the impedance of a suspension. This value can, for example, be directly the impedance value Z be.

[0114] In a real measurement setup, an impedance measurement value Z sig from a measured voltage U sig and a measured current I sig However, due to the signal processing in the measuring setup, this impedance measurement value may differ from the impedance value applied to the measuring electrodes. Z mes s. The conversion between the impedance measurement value Z sig and the impedance value applied to the measuring electrodes Z mes s can be determined by a transfer function G el the measuring arrangement or an inverse correction function G el − 1 expressed as: Z sig ⇄ G el − 1 G el Z mess .

[0115] In reality, the impedance value applied to the measuring electrodes is Z mes s is not the desired impedance of the suspension, but is composed of an impedance value Z c.c , which depends on the measuring geometry, and a variety of interferences, such as parasitic capacitances, double layer formation on the electrode surfaces, contact resistances, etc. The interferences can be collectively referred to as parasitic influences Z par which can distort the measurement. The totality of the interference can depend on a variety of parameters, such as temperature, conductivity of the solution, frequency of the excitation current, ion concentration in the solution, material and properties of the electrodes, etc. The notation for these parameters can be summarized as a parameter set { ψ i } The parameters can be abbreviated in various ways to Z par contribute and thus as different Z par i ψ i Thus, the impedance value applied to the measuring electrodes Z mes s as a function F can be expressed according to the following relationship: Z sig ⇄ G el − 1 G el F Z par i ψ i , Z c . c . .

[0116] The designation Z c.c . is used because the impedance of a cell suspension can be described in good approximation by the so-called Cole-Cole impedance.

[0117] As described above, the impedance value Z c . c . depends on the measurement geometry. The measurement geometry is also referred to here as the geometry of the measuring cell of a pair of measuring electrodes. The desired impedance value Z depends on the measurement geometry-dependent impedance value Z c . c . about the cell constant λ The following relationship applies: Z c . c . = λ j iω ϵ cole − cole = λ j Z .

[0118] For the cell constant λ j of a j-th pair of measuring electrodes: λ j = 1 σ Lösung Δϕ j ∫ J → d A → , where ∫ J d A the area integral of the current densities and Δϕ ( j )< is the potential difference of the j-th pair of measuring electrodes.

[0119] Thus, the impedance value applied to the measuring electrodes Z mes s can be expressed according to the following relationship: Z sig ⇄ G el − 1 G el F Z par i ψ i , λ j Z .

[0120] The function F can be expressed as a polynomial of λ j Z be developed. This results in: Z sig ⇄ G el − 1 G el ∑ n 1 n ! a n Z par i ψ i λ j n Z n .

[0121] For the j-th pair of measuring electrodes, the second-order expansion is: G el − 1 Z sig j = a 0 Z par i + λ j a 1 Z par i Z + O 2 , where O (2) is an abbreviation for the quadratic part of the polynomial expansion.

[0122] Assuming that the precursors a n and the parasitic influences Z par i are identical for different cell geometries, and if one further assumes a series connection of parasitic influences and cell impedance, the difference between two impedance measurements is: G el − 1 Z sig 1 − G el − 1 Z sig 2 = λ 1 − λ 2 a 1 Z par i Z + O 2 , where O (2) is an abbreviation for all quadratic parts of the polynomial expansions.

[0123] If we continue to assume thatO (2) and the higher order components are negligible and that a 1 Z par i is a constant in good approximation, one arrives at the above formula for calculating the value indicating the impedance of the suspension Z from two impedance measurements.

[0124] It has been found that under the assumptions described above, measurement results of very high accuracy are possible.

[0125] A further development of the above considerations leads to the further formula mentioned above for the calculation of the value indicating the impedance of the suspension Z from three impedance measurements.

[0126] Fig. 9 shows, purely qualitatively, the curve 200 of the permittivity ε of a cell population, plotted against the excitation frequency f. The curve 200 is a purely exemplary curve derived from a plurality of permittivity values ​​determined using the method described above. For example, the curve 200 may have been derived from the plurality of permittivity values ​​using a Cole-Cole fitting.

[0127] From the curve 200, the following characteristics of the cell population can be derived. In Fig. 9 It is qualitatively shown that in front of a frequency f ch characteristic of the β-dispersion region 202 there is a plateau region 204 in which the permittivity ε changes only slightly with frequency compared to the area around the characteristic frequency f ch , and that after the characteristic frequency f ch there is a further plateau region 206 which is different from the plateau region 204 in front of the characteristic frequency f ch and in which the permittivity ε, again compared to the area around the characteristic frequency f ch , also does not change greatly with frequency.

[0128] If one compares a permittivity value ε 1 representing the permittivity ε at an excitation frequency f 1 in the plateau region 204 with a permittivity value ε 2 at an excitation frequency f 2 in the plateau region 206, a difference value Δε between the two permittivity values ​​can be determined from the permittivity values ​​ε 1 and ε 2 determined at the excitation frequencies f 1 and f 2, respectively. The difference value Δε is a measure of the number of living cells contained in the cell population. The alternative permittivity curve 210 indicated by two dots and three dashes would lead to a larger Δε at the respective excitation frequencies f 1 and f 2 , which allows the conclusion that the cell population for which the permittivity curve 210 was obtained has more living cells in the same volume than the cell population underlying the permittivity curve 200.

[0129] A change in the characteristic frequency f ch indicates a change in the size of the cells or their physiology. A permittivity curve 220 with two dots and a dash indicates a higher characteristic frequency f ch in Fig. 9 . The characteristic frequency f ch can be determined from the inflection point of the curve 200 between the plateau region 204 and the plateau region 206.

[0130] The slope of the permittivity curve at the point of its characteristic frequency f ch is a measure of the cell size distribution, with increasing slope indicating a more heterogeneous cell size distribution and flatter slopes of the permittivity curve 200 at the location of the characteristic frequency f ch indicating more homogeneous cell size distributions.

[0131] The Fig. 9 The permittivity curves shown can in particular be the curves of the real parts of the determined permittivity values.

[0132] In the exemplary embodiment of the Fig. 9 is f 1 = 50 kHz and f 2 = 20 MHz.

[0133] Sensors according to exemplary embodiments of the invention enable highly accurate determination of permittivity values ​​over such a wide frequency range, allowing the β-dispersion region to be described very extensively for many cell populations. In particular, the sensor and the method for determining a value indicative of the impedance of a suspension according to exemplary embodiments of the invention are suitable for cell populations with a conductivity of a few 0.1 mS / cm to 100 mS / cm and with a permittivity of a few pF / cm to several hundred pF / cm.

[0134] An exemplary application for the sensor and method for determining a value indicative of the impedance of a suspension according to exemplary embodiments of the invention is fermentation processes, for example, in the brewing of beverages. However, the invention is generally broadly applicable for determining values ​​indicative of the impedance of a suspension and for the subsequent determination of permittivity values.

[0135] Although the invention has been described with reference to exemplary embodiments, it will be apparent to one skilled in the art that various modifications may be made without departing from the scope of the invention. The invention is not intended to be limited to the specific embodiments described. Rather, it includes all embodiments falling within the appended claims.

Claims

1. A method for determining a value indicative of the impedance of a suspension in the framework of an impedance spectroscopy, comprising the following steps: generating an excitation current through the suspension, the excitation current oscillating at an excitation frequency, wherein the excitation current through the suspension is generated by means of a pair of excitation electrodes (8, 10), determining a first impedance measurement value on the basis of the excitation current and a first voltage at a first pair of measurement electrodes (11, 12), determining a second impedance measurement value on the basis of the excitation current and a second voltage at a second pair of measurement electrodes (11, 13; 13, 14), wherein the first pair of measurement electrodes and the second pair of measurement electrodes are different pairs of measurements electrodes, determining the value indicative of the impedance of the suspension by relating the first impedance measurement value and the second impedance measurement value, wherein determining the value indicative of the impedance of the suspension comprises determining the difference between a first adjusted impedance value and a second adjusted impedance value, wherein the first adjusted impedance value and the second adjusted impedance value are obtained by applying a correction function to the first impedance measurement value and the second impedance measurement value, the correction function representing the transmission behavior of the measurement arrangement, wherein the relating of the first impedance measurement value and the second impedance measurement value is carried out according to the following formula: Z = k 1 λ 1 − λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 2 , wherein Zsig|1 denotes the first impedance measurement value, Zsig|2 denotes the second impedance measurement value, Gel-1 denotes the correction function representing the transmission behavior of the measurement arrangement, λ1 denotes a first geometry factor representing the measurement geometry of the first pair of measurement electrodes, λ2 denotes a second geometry factor representing the measurement geometry of the second pair of measurement electrodes, and k denotes a proportionality constant.

2. The method according to claim 1, wherein said first pair of measurement electrodes comprises a first measurement electrode (11) and a second measurement electrode (12), and wherein said second pair of measurement electrodes comprises said first measurement electrode (11) and a third measurement electrode (13), or wherein the first pair of measurement electrodes comprises a first measurement electrode (11) and a second measurement electrode (12), and wherein the second pair of measurement electrodes comprises a third measurement electrode (13) and a fourth measurement electrode (14).

3. The method according to any of the preceding claims, further comprising: measuring the first voltage at the first pair of measurement electrodes, and measuring the second voltage at the second pair of measurement electrodes, wherein measuring the first voltage and measuring the second voltage are performed substantially simultaneously, or further comprising: measuring the first voltage at the first pair of measurement electrodes, and measuring the second voltage at the second pair of measurement electrodes, wherein measuring the first voltage and measuring the second voltage are performed in a time-shifted manner.

4. The method according to any of the preceding claims, wherein determining the first impedance measurement value and determining the second impedance measurement value comprises: sampling the excitation current, sampling the first voltage, and sampling the second voltage; wherein the method in particular further comprises the steps of: setting a first sampling rate for sampling the excitation current, setting a second sampling rate for sampling the first voltage, and setting a third sampling rate for sampling the second voltage, wherein the first sampling rate, the second sampling rate and the third sampling rate are set to at least 4 times the excitation frequency of the excitation current, in particular to substantially 4 times the excitation frequency of the excitation current.

5. The method according to claim 4, wherein the step of determining the first impedance measurement value comprises performing a first complex Fourier transform on the basis of the sampling values of the excitation current and the sampling values of the first voltage, and wherein the step of determining the second impedance measurement value comprises performing a second complex Fourier transform on the basis of the sampling values of the excitation current and the sampling values of the second voltage.

6. The method according to any of the preceding claims, further comprising: determining a third impedance measurement value on the basis of the excitation current and a third voltage at a third pair of measurement electrodes, and determining the value indicative of the impedance of the suspension by relating the first impedance measurement value, the second impedance measurement value, and the third impedance measurement value; wherein determining the value indicative of the impedance of the suspension comprises determining a first difference between the first adjusted impedance value and the second adjusted impedance value and determining a second difference between the first adjusted impedance value and a third adjusted impedance value and determining a third difference between the second adjusted impedance value and the third adjusted impedance value, wherein the first adjusted impedance value, the second adjusted impedance value and the third adjusted impedance value are obtained by applying the correction function to the first impedance measurement value, the second impedance measurement value and the third impedance measurement value.

7. The method according to claim 6, wherein determining the value indicative of the impedance of the suspension comprises determining a first difference between the first geometry factor and the second geometry factor and determining a second difference between the first geometry factor and a third geometry factor and determining a third difference between the second geometry factor and the third geometry factor, wherein the third geometry factor represents the measurement geometry of the third pair of measurement electrodes; wherein determining the value indicative of the impedance of the suspension is in particular carried out according to the following formula: Z 2 = k 2 λ 3 G el − 1 Z sig 2 − G el − 1 Z sig 1 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 + + k 2 λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 3 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 + + k 2 λ 1 G el − 1 Z sig 3 − G el − 1 Z sig 2 λ 1 − λ 2 λ 1 − λ 3 λ 2 − λ 3 , wherein Zsig|3 denotes the third impedance measurement value, λ3 denotes a third geometry factor that represents the measurement geometry of the third pair of measurement electrodes, and k2 denotes a proportionality constant.

8. A method for determining a value indicative of the impedance of a suspension in the framework of an impedance spectroscopy, comprising the following steps: generating an excitation voltage, oscillating at an excitation frequency, applied to the suspension, wherein the excitation voltage through the suspension is generated by means of a pair of excitation electrodes (8, 10), determining a first impedance measurement value on the basis of the excitation voltage and a first current through a first pair of measurement electrodes, determining a second impedance measurement value on the basis of the excitation voltage and a second current through a second pair of measurement electrodes, wherein the first pair of measurement electrodes and the second pair of measurement electrodes are different pairs of measurements electrodes, determining the value indicative of the impedance of the suspension by relating the first impedance measurement value and the second impedance measurement value, wherein determining the value indicative of the impedance of the suspension comprises determining the difference between a first adjusted impedance value and a second adjusted impedance value, wherein the first adjusted impedance value and the second adjusted impedance value are obtained by applying a correction function to the first impedance measurement value and the second impedance measurement value, the correction function preferably representing the transmission behavior of the measurement arrangement, wherein the relating of the first impedance measurement value and the second impedance measurement value is carried out according to the following formula: Z = k 1 λ 1 − λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 2 , wherein Zsig|1 denotes the first impedance measurement value, Zsig|2 denotes the second impedance measurement value, Gel-1 denotes the correction function representing the transmission behavior of the measurement arrangement, λ1 denotes a first geometry factor representing the measurement geometry of the first pair of measurement electrodes, λ2 denotes a second geometry factor representing the measurement geometry of the second pair of measurement electrodes, and k denotes a proportionality constant.

9. A method for deriving at least one characteristic property of a suspension, comprising the steps of: performing the method for determining a value indicative of the impedance of a suspension according to any of the preceding claims a plurality of times, using a plurality of different excitation frequencies and determining a plurality of values indicative of the impedance of the suspension for the plurality of different excitation frequencies, deriving a plurality of values indicative of the permittivity of the suspension based on the plurality of values indicative of the impedance of the suspension, and deriving the at least one characteristic property of the suspension by relating the plurality of values indicative of the permittivity of the suspension.

10. The method according to claim 9, wherein said method for determining a value indicative of the impedance of a suspension is performed for between 2 and 50 different excitation frequencies, in particular for between 10 and 40 different excitation frequencies, further in particular for between 20 and 30 different excitation frequencies; and / or wherein the different excitation frequencies are from a frequency range from 100 kHz to 10 MHz, in particular from a frequency range from 50 kHz to 20 MHz.

11. The method according to claim 9 or 10, wherein deriving the at least one characteristic property of the suspension includes generating a curve of the values indicative of the permittivity of the suspension over the different excitation frequencies; and / or wherein the suspension is a cell population and wherein the at least one characteristic property of the suspension comprises at least one property of number of living cells, size of the cells and homogeneity of the cells.

12. A sensor (2) for determining a value indicative of the impedance of a suspension, comprising: an oscillator circuit (16), a pair of excitation electrodes (8, 10) coupled to the oscillator circuit, wherein an excitation current through the suspension, oscillating at an excitation frequency, can be generated across the pair of excitation electrodes by means of the oscillator circuit, at least three measurement electrodes for measuring a first voltage in the suspension between a first pair of the at least three measurement electrodes and a second voltage in the suspension between a second pair of the at least three measurement electrodes, wherein the first pair of measurement electrodes and the second pair of measurement electrodes are different pairs of measurements electrodes, and a data processing device (40) configured to determine a first impedance measurement value on the basis of the excitation current and the first voltage, to determine a second impedance measurement value on the basis of the excitation current and the second voltage, and to determine the value indicative of the impedance of the suspension by relating the first impedance measurement value and the second impedance measurement value; wherein the data processing device (40) is configured to determine the value indicative of the impedance of the suspension via determining the difference between a first adjusted impedance value and a second adjusted impedance value, wherein the data processing device is configured to determine the first adjusted impedance value and the second adjusted impedance value by applying a correction function to the first impedance measurement value and the second impedance measurement value, wherein the correction function represents the transmission behavior of the measurement arrangement, wherein the data processing device (40) is configured to determine the value indicative of the impedance of the suspension according to the following formula: Z = k 1 λ 1 − λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 2 , wherein Zsig|1 denotes the first impedance measurement value, Zsig|2 denotes the second impedance measurement value, Gel-1 denotes the correction function representing the transmission behavior of the measurement arrangement, λ1 denotes a first geometry factor representing the measurement geometry of the first pair of the at least three measurement electrodes, λ2 denotes a second geometry factor representing the measurement geometry of the second pair of the at least three measurement electrodes, and k denotes a proportionality constant.

13. The sensor (2) according to claim 12, wherein the at least three measurement electrodes are arranged between the pair of excitation electrodes (8, 10).

14. The sensor (2) according to claim 12 or 13, wherein the at least three measurement electrodes are at least four measurement electrodes, wherein the first pair of the at least four measurement electrodes comprises a first measurement electrode (11) and a second measurement electrode (12) and wherein the second pair of the at least four measurement electrodes comprises a third measurement electrode (13) and a fourth measurement electrode (14); wherein the third and fourth measurement electrodes (13, 14) are in particular arranged between the first and second measurement electrodes (11, 12) and / or wherein the third and fourth measurement electrodes (13, 14) are in particular arranged on a different side of the sensor than the first and second measurement electrodes (11, 12).

15. The sensor (2) according to any of claims 12 to 14, wherein the oscillator circuit (16) is coupled to the pair of excitation electrodes (8, 10) via a transformer (22), wherein the transformer (22) in particular has a parallel capacitance of 0.5 to 10 pF, further in particular of 1 to 5 pF.

16. A sensor (2) for determining a value indicative of the impedance of a suspension, comprising: an oscillator circuit (16), a pair of excitation electrodes (8, 10) coupled to the oscillator circuit, wherein an excitation voltage, oscillating at an excitation frequency, applied to the suspension can be generated across the pair of excitation electrodes by means of the oscillator circuit, at least three measurement electrodes for measuring a first current in the suspension between a first pair of the at least three measurement electrodes and a second current in the suspension between a second pair of the at least three measurement electrodes, wherein the first pair of measurement electrodes and the second pair of measurement electrodes are different pairs of measurements electrodes, and a data processing device (40) configured to determine a first impedance measurement value on the basis of the excitation voltage and the first current, to determine a second impedance measurement value on the basis of the excitation voltage and the second current, and to determine the value indicative of the impedance of the suspension by relating the first impedance measurement value and the second impedance measurement value; wherein the data processing device (40) is configured to determine the value indicative of the impedance of the suspension via determining the difference between a first adjusted impedance value and a second adjusted impedance value, wherein the data processing device is configured to determine the first adjusted impedance value and the second adjusted impedance value by applying a correction function to the first impedance measurement value and the second impedance measurement value, wherein the correction function represents the transmission behavior of the measurement arrangement, wherein the data processing device (40) is configured to determine the value indicative of the impedance of the suspension according to the following formula: Z = k 1 λ 1 − λ 2 G el − 1 Z sig 1 − G el − 1 Z sig 2 , wherein Zsig|1 denotes the first impedance measurement value, Zsig|2 denotes the second impedance measurement value, Gel-1 denotes the correction function representing the transmission behavior of the measurement arrangement, λ1 denotes a first geometry factor representing the measurement geometry of the first pair of the at least three measurement electrodes, λ2 denotes a second geometry factor representing the measurement geometry of the second pair of the at least three measurement electrodes, and k denotes a proportionality constant.

17. A computer program comprising program instructions which, when executed on a data processing system, perform a method according to any of claims 1 to 11, wherein the individual steps of the method are initiated by the program instructions and executed by components of a sensor or are executed in the data processing system itself.