Method and sensor for determining the permittivity of a cell population

Patent metadata

Field	Value
Publication number	US-11480536-B2
Application number	US-201816768200-A
Country	US
Kind code	B2
Filing date	Nov 29, 2018
Priority date	Nov 30, 2017
Publication date	Oct 25, 2022
Grant date	Oct 25, 2022

Abstract

A method for determining a value indicative of the permittivity of a cell population in the context of impedance spectroscopy comprises the following steps: generating an excitation current through the cell population, which oscillates with an excitation frequency; measuring a voltage in the cell population between a first measuring electrode ( 12 ) and a second measuring electrode ( 14 ); sampling the excitation current, wherein first sampled values for the excitation current are generated; sampling the voltage between the first measuring electrode ( 12 ) and the second measuring electrode ( 14 ), wherein second sampled values for the voltage between the first measuring electrode and the second measuring electrode are generated; and determining the value indicative of the permittivity of the cell population on the basis of the first sampled values and the second sampled values.

First claim

The invention claimed is:

1. A method for determining a value indicative of the permittivity of a cell population in the context of impedance spectroscopy, comprising the following steps:
generating an excitation current through the cell population, which oscillates with an excitation frequency;
measuring a voltage in the cell population between a first measuring electrode and a second measuring electrode;
sampling the excitation current, wherein first sampled values for the excitation current are generated;
sampling the voltage between the first measuring electrode and the second measuring electrode, wherein second sampled values for the voltage between the first measuring electrode and the second measuring electrode are generated, determining the value indicative of the permittivity of the cell population on the basis of the first sampled values and the second sampled values;
determining a spectral power of the excitation current and that spectral component of the voltage that has the excitation frequency;
determining the total power of excitation current and voltage between the first measuring electrode and the second measuring electrode; and
determining a measure for the measurement accuracy of the value indicative of the permittivity of the cell population on the basis of said spectral power and the total power.

2. The method according to claim 1 , further comprising the steps of:
setting a first sampling rate for sampling the excitation current; and
setting a second sampling rate for sampling the voltage between the first measuring electrode and the second measuring electrode,
wherein the first sampling rate and the second 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.

3. The method according to claim 1 , wherein the excitation frequency of the excitation current is between 50 kHz and 20 MHz.

4. The method according to claim 1 , wherein the step of determining the value indicative of the permittivity of the cell population includes applying a complex Fourier transformation to the first sampled values and the second sampled values.

5. The method according to claim 1 , wherein the step of determining the value indicative of the permittivity of the cell population comprises at least one of the following steps:
determining the amplitude of the oscillating excitation current;
determining that spectral component of the voltage that has the excitation frequency; and
determining the phase shift between excitation current and said spectral component of the voltage.

6. The method according to claim 1 , wherein generating the excitation current through the cell population, which oscillates with the excitation frequency, comprises a galvanic de-coupling between an alternating current source, outputting the excitation current, and the cell population.

7. The method according to claim 1 ,
wherein the measure for the measurement accuracy of the value indicative of the permittivity of the cell population is the signal-to-noise ratio on the basis of said spectral power and the total power.

8. A method for deriving at least one characteristic property of a cell population, comprising the following steps:
performing the method for determining a value indicative of the permittivity of a cell population according to claim 1 several times, using a plurality of different excitation frequencies, and determining a plurality of values indicative of the permittivity of the cell population for the plurality of different excitation frequencies; and
deriving the at least one characteristic property of the cell population by relating the plurality of values indicative of the permittivity of the cell population.

9. The method according to claim 8 , wherein said method for determining a value indicative of the permittivity of a cell population is carried out for between 2 and 50 different excitation frequencies, in particular for between 10 and 40 different excitation frequencies, more particularly for between 20 and 30 different excitation frequencies.

10. The method according to claim 8 , wherein the different excitation frequencies are from a frequency range of 100 kHz to 10 MHz, in particular from a frequency range of 50 kHz to 20 MHz.

11. The method according to claim 8 , wherein each instance of said several times of performing the method for determining a value indicative of the permittivity of a cell population takes between 10 ms and 100 ms, in particular between 30 ms and 70 ms.

12. The method according to claim 8 , wherein 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.

13. A computer program which contains program instructions which, when executed on a data processing system, carry out a method according to claim 1 .

14. A cell population sensor for determining a value indicative of the permittivity of a cell population, comprising:
an oscillator circuit;
a first excitation electrode and a second excitation electrode which are coupled to the oscillator circuit, wherein an excitation current through the cell population, which oscillates with an excitation frequency, can be generated by means of the oscillator circuit via the first and second excitation electrodes;
a first measuring electrode and a second measuring electrode for measuring a voltage in the cell population between the first and second measuring electrodes,
a first sampling circuit which is coupled to the first excitation electrode and/or the second excitation electrode and in operation provides first sampled values for the oscillating excitation current;
a second sampling circuit which is coupled to the first and second measuring electrodes and in operation provides second sampled values for the voltage between the first and second measuring electrodes; and
a data processing device which is coupled to the first sampling circuit and the second sampling circuit and which is configured to determine the value indicative of the permittivity of the cell population on the basis of the first sampled values and the second sampled values,
wherein the data processing device is configured to determine a spectral power of the excitation current and that spectral component of the voltage that has the excitation frequency and to determine the total power of excitation current and voltage between the first measuring electrode and the second measuring electrode, and wherein the data processing device is further configured to determine a measure for the measuring accuracy of the value indicative of the permittivity of the cell population on the basis of the said spectral power and the total power.

15. The cell population sensor according to claim 14 , wherein the first sampling circuit has a first settable sampling rate and wherein the second sampling circuit has a second settable sampling rate,
wherein the first settable sampling rate and the second settable sampling rate are settable to at least 4 times the excitation frequency of the excitation current, in particular substantially to 4 times the excitation frequency of the excitation current.

16. The cell population sensor according to claim 14 , wherein the oscillator circuit is configured to set the excitation frequency in a frequency range from 100 kHz to 10 MHz, in particular in a frequency range from 50 kHz to 20 MHz.

17. The cell population sensor according to claim 14 , wherein the data proces

Assignees

• Hamilton Bonaduz Ag

Inventors

• Imhof Manuel

Classifications

• G01N33/48735 Primary

  Investigating suspensions of cells, e.g. measuring microbe concentration (by chemical means C12Q1/04; colony counters C12M1/34; concentration of particle suspensions in general G01N15/06) · CPC title

• G01N27/02

  by investigating impedance · CPC title

• G01N27/028

  Circuits therefor (measuring impedance per se G01R27/02) · CPC title

• G01N33/4833

  of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735) · CPC title

• G01N27/026 Primary

  Dielectric impedance spectroscopy (electrochemical impedance spectroscopy for measuring corrosion G01N17/02) · CPC title