WO2002040982A1

WO2002040982A1 - Method and apparatus for determining at least one property of a biological liquid

Info

Publication number: WO2002040982A1
Application number: PCT/NL2001/000837
Authority: WO
Inventors: Gheorghe Aurel Marie Pop
Original assignee: Martil Instruments B.V.
Priority date: 2000-11-17
Filing date: 2001-11-19
Publication date: 2002-05-23
Also published as: NL1016633C2; AU2002222785A1

Abstract

The invention relates to a method for determining at least one property of a flowing biological liquid, comprising of: generating an alternating current electrical field at a determined frequency in the biological liquid for a determined time; measuring during this determined time a measurement signal of the electrical impedance between at least two points in the biological liquid; and comparing the measurement signal with a predetermined relation between the measured impedance and the property of the liquid, wherein the biological liquids is not blood. The invention also relates to an apparatus for determining at least one property of a biological liquid, comprising: a tube for receiving a flow of biological liquid; means for generating an alternating current electrical field with a determined frequency in the biological liquid for a determined time; means for measuring the electrical impedance between at least two point in the biological liquid; and a recording device connectable to the measuring means for recording the measured electrical impedance and/or impedance change in the biological liquid; in addition to a transport system for a biological liquid, comprising least one pumping means and a tube.

Description

METHOD AND APPARATUS FOR DETERMINING AT LEAST ONE PROPERTY OP A BIOLOGICAL LIQUID

The present invention relates to a method and apparatus for determining at least one property of a biological liquid.

Liquids generally have a particular viscosity which is determined by the ratio between the shear stress and shear rate. All liquids are characterized rheologically by the manner in which this ratio changes with changes in the shear rate. For so-called Newtonian liquids it is the case that the shear stress is proportional to the shear rate in laminar flows, i.e. the viscosity is constant. It is possible to speak of non-Newtonian behaviour of a liquid if the viscosity thereof varies subject to the shear rate. Poiseuille's law also refers only to liquids with a viscosity which remains constant at differing degrees of (laminar) flow. This law cannot however be automatically applied to liquids with non- Newtonian behaviour. Only if a liquid consists of small particles of equal size and the liquid is homogeneous will a liquid behave in Newtonian manner. Liquids which consist of molecules of a certain size or of a high concentration of particles in suspension (such as for instance red blood cells in the blood) , will behave to a greater or lesser extent in non-Newtonian manner. Most biological liquids are generally of such a nature; they are suspensions of cells or of proteins or other macromolecules which are of differing size and which influence each other, such as for instance due to van der aals forces, particularly at a lower shear rate. The viscosity hereby changes. It is known to measure the viscosity of biological liquids by means of so-called "cone plate" viscosimeters, wherein the shear rate can be adjusted and the shear stress calculated; the ratio of the two parameters then denotes the viscosity. Measurement of the viscosity of biological liquids in this way is however a laborious and time-consuming procedure. It is known to measure the conductivity of a flowing liquid between at least two points (Polytechnisch tijdschrift (Polytechnic journal) (NL) , part 25, no. 7, 3 April 1970, pp. 262-266) . Arranged as part of a transport system is a measuring cell provided with two measuring electrodes placed between two voltage electrodes which apply a direct current electrical field. The measured value for the conductivity is used to determine the concentration of electrolytes in the liquid.

The object of the present invention is to provide a method for determining at least one property of a flowing biological liquid, wherein the above stated drawbacks are at least reduced. This object is achieved by the invention with a method comprising of:

(a) providing a transport system for causing a biological liquid to flow;

(b) generating an alternating current electrical field at a determined frequency in the biological liquid for a determined time;

(c) measuring during this determined time a measurement signal of the electrical impedance between at least two points in the biological liquid; and (d) comparing the measurement signal with a predetermined relation between the measured impedance and the properties of the liquid.

Using the method according to the invention diverse properties of a flowing biological liquid other than blood can be determined in simple and reliable manner. In a particular embodiment thereof, the method further comprises of determining the temperature of the biological liquid during the impedance measurement, wherein the measuring signal is compared to a predetermined relation between the measured impedance, the temperature and the properties of the liquid. In this manner a relation can be determined between temperature changes in the biological liquid and the measured electrical impedance, and corrections can be made for the temperature. With the method according to the invention the impedance is determined over a part of the flowing biological liquid in a transport system. By making use of two measuring points the impedance of the liquid is measured in the part between the two measuring points. The method according to the invention is suitable for determining different properties of various biological liquids. The biological liquid is preferably not blood. It is possible here to envisage saliva, mucus or milk. The biological liquid is preferably of mineral origin. The biological liquid particularly comprises oil . ,

The invention also relates to an apparatus for determining at least one property of a biological liquid as according to claim 7.

It is advantageous to connect the voltage generating means to an alternating current source. A pair of voltage electrodes is preferably provided. Measurement of the impedance of blood hereby becomes possible in efficient manner. In order to ensure a homogeneous electrical field, the distances between the electrodes are chosen to be more than twice the diameter of the tube through which the biological liquid flows. The apparatus according to the invention is preferably embodied with a set of measuring electrodes. The impedance of the liquid can hereby be measured between the measuring electrodes .

The measuring means are in contact with the biological liquid. The measuring means are preferably located in the biological liquid. The measuring means are otherwise enclosed with substantially insulating material and a connecting wire to the recording device, in a special embodiment the measuring means are received in a tube of preferably insulating material, wherein the inner surface of the tube along which the liquid flows is substantially flat, so that no turbulence occurs in the flow. The measuring means do not protrude into the tube. This prevents the possibility of liquid or contamination accumulating against the measuring means. The electrodes are preferably arranged at regular mutual distances in the longitudinal direction of the tube. A homogeneous electrical field is hereby obtained in the blood. Otherwise known from GB 2 260 407 is a container of insulating material in which a sample is arranged in static manner. The container comprises a number of voltage electrodes. Each voltage electrode is connected to an alternating current source of a known frequency. Each of the voltage electrodes will apply an alternating current electrical field in the sample. Measuring electrodes are also arranged. The measurement signal is filtered in a circuit to the determined frequency of the alternating current source. None of the electrodes make contact with the sample. Using the assembly of electrodes a measurement value is determined for the capacitance and induction of the sample. The measurement value is used to determine a property of the sample . The relation between measurement value and the property is determined by a calibration measurement with a sample with a known value for the property to be measured.

A filter is preferably arranged for particles which do have an influence on the impedance but not on the viscosity of the liquid or other property being determined. This relates preferably to transport systems in the form of circulation systems, and more particularly of lubricating oil in motors. The invention can herein be used to optimize the (through) flow on the basis of measured properties, wherein the invention is applied to determine the viscosity of the lubricating oil . The oil does however become fouled in the course of time with conductive particles such as iron particles. The conducting properties of the fouling influence the impedance measurement. A filter is arranged to prevent this.

The present invention will be elucidated with reference to the annexed figures, in which figure 1 is a schematic view of a preferred embodiment of the apparatus according to the invention; figure 2 shows two graphs in which the measured impedance signal is plotted as a function of time. A: measured impedance signal (ZO) ; B: measured impedance change (delta Z) . figure 3 shows a detail of the preferred embodiment of the apparatus according to the invention shown in figure 1, wherein a biological liquid with a number of particles is indicated; and figure 4 shows two other preferred embodiments of the apparatus according to the invention.

Figure 1 shows a measuring cell 1. A liquid 2 flows in the direction of arrow 3 through a tube 4 which forms part of a transport system (not further shown) for a biological liquid. Measuring cell 1 is provided at two points with two voltage electrodes 5, 6. These latter are connected to an adjustable alternating current source 7. Situated between voltage electrodes 5, 6 are two measuring electrodes 8, 9, preferably of platinum, with which the impedance in the flowing liquid 2 is measured. The measurement signals are collected in an acquisition means 10.

A good correlation has been found in blood between the viscosity and particular electrical impedance characteristics measured at different frequencies between 1 kHz and 5000 kHz (see PCT/NL00/00378 and the Netherlands patent application number 1016247) . In blood the higher impedance at lower shear rate is attributed mainly to the occurrence of "rouleaux" formation between the red blood cells. A consequence hereof may be that the ordered arrangement present between the red blood cells in the flow direction at a higher shear rate is present to an increasingly lesser extent at a lower shear rate. The more random position and configuration of the erythrocytes at the lower flow speed, which is herein further enhanced by a reversible network of the macromolecules present in the blood, results in a disruption of the induced electrical field, which is expressed in measurement of a higher impedance in respect of both the resistive and capacitive components. "Rouleaux" formation as in blood does not occur in an oil . The macromolecules present in the oil influence each other, for instance in the form of van der Waals forces, whereby they attract each other and can associate with each other. In addition, asymmetrical molecules of a determined length and three-dimensional structure will be ordered in a special manner under the influence of a higher shear rate. The extent of this ordering will have an influence on the viscosity, and this will be expressed in a change in the electrical impedance characteristics. The more ordered the macromolecules in the flow direction, the lower the viscosity and the lower the measured electrical impedance . With the method according to the invention different properties of biological liquids can be determined. In a preferred embodiment according to the invention the property to be determined comprises the viscosity of the biological liquid. The relation found between the measured impedance signal and the viscosity of the liquid can for instance be used in modifying the viscosity of the oil by means of adding viscosity- reducing substances such that for instance the optimal viscosity can be determined at a specific shear rate. The shear rate is generally determined by dividing four times the average flow speed of the liquid by the radius of the tube through which the liquid flows. Conversely, when it is not possible to add viscosity-reducing substances, a flow speed of the biological liquid, such as for instance oil, or a size of the tube can be chosen such that a shear rate results wherein the viscosity is lowest. The transport for instance of oil over large distances through large pipes will hereby cost less energy. The viscosity properties for instance of oil as lubricant can also be improved in this way when it is used in motors. The result of optimizing the viscosity is therefore not only a decrease in the energy requirement but also a reduction in wear. Figure 2A shows a graph showing an impedance measurement through time. The impedance (Y-axis) is measured through time (X-axis) .

Figure 2B shows a graph showing the change (Delta Z signal) of the impedance (Y-axis) through time (X-axis) . In another preferred embodiment according to the invention the property of the biological liquid comprises the degree of purity of this liquid. Particular contaminants in the biological liquid of a determined size and consistency can be detected with the method according to the invention, whereby the purity in the liquid can be continuously monitored. Small particles (smaller than 100 micrometres) with an impedance other than oil will manifest themselves as a sudden change in the impedance signal (see figure 2) . The magnitude of this change depends on the difference in specific impedance between the particle and the biological liquid, such as for instance oil. During the passage of air particles a large deflection in the measured impedance signal will for instance occur due to the considerably higher specific resistance of air relative to oil or other biological liquid. The change in the measured impedance signal will be less great during passage of particles 11 of a different consistency, such as for instance in the case of small solid aggregates with a specific resistance which differs to a lesser extent from the specific resistance of the biological liquid. The measured impedance signal will therefore not only indicate whether particles are passing through, such as for instance air bubbles, but will also provide insight into the consistency of these particles by means of characterizing the measured impedance at different frequencies. It is for instance possible in this way to determine whether there is air contamination, owing to for instance a leakage in the pipe system, or solid contamination by a material other than the biological liquid itself. In both cases the treatment of the problem will be very different. When there indications for solid aggregates, it will be possible for instance to envisage a particular form of filtering, and in the case air is present it will be necessary to look for a leakage in the pipe system. When a continuous flow speed of the liquid is known, the total time in the change of the impedance signal will moreover provide information about the diameter of particles 11 parallel to the line between measuring electrodes 8, 9 (see figure 3) .

The determined frequency of the alternating current preferably lies between 1 and 5000 kHz. The average measured electrical impedance at different frequencies between 1 and 5000 kHz will provide an impedance characteristic for a specific liquid, on the basis of which a judgement can be made concerning the liquid at a determined measured impedance signal. As is known, impedance has a resistive/conductive component as well as a capacitive component, a real and an imaginary part.

The invention further relates to and provides an apparatus for determining at least one property of a flowing biological liquid, comprising: means for generating an electrical alternating current electrical field with a determined frequency in the biological liquid for a determined time; means for measuring the electrical impedance between at least two points in the biological liquid; and a recording device connectable to the measuring means for recording the measured electrical impedance and/or impedance change in the biological liquid.

Using the apparatus according to the invention diverse properties of a biological liquid can be determined in simple and reliable manner.

In a particularly suitable embodiment of the apparatus according to the invention the apparatus also comprises means for measuring the temperature of the biological liquid, such as for instance a thermometer, in order to determine the temperature at which the impedance is measured.

The apparatus according to the invention can be used to determine diverse properties of various biological liquids other than oil. In a particularly suitable embodiment of the apparatus the biological liquid comprises oil.

A particularly suitable embodiment of the apparatus further comprises a hollow tube for transporting the biological liquid in which the voltage generating means and the measuring means are arranged (see figure 1) . The transport tube preferably has a high electrical resistance. In order to ensure that the liquid flowing through the tube will have a laminar flow profile, the length of the transport tube preferably corresponds to at least twelve times the diameter thereof. When the pipe system through which the biological liquid is transported is for instance a large one, the apparatus comprising the hollow transport tube 4 in which the voltage generating means 5, 6 and measuring means 8, 9 are arranged can be introduced as a temporary measuring device 1 in the large pipe 4 (see figure 4A) . The direction of the transport tube will then have to be placed such that it runs parallel to the flow direction 9 of the biological liquid. Measuring device 1 can be arranged at a plurality of locations within the large diameter of a transport tube, so that for instance the viscosity can be determined at different locations within a larger diameter. This is because in non- Newtonian liquids the shear rate varies in non-linear manner with the radius over the distance between the wall and the centre of the tube, so that in the case of tubes with large diameters differences may be present in the viscosity at different locations within the large diameter. Using the apparatus according to the invention a viscosity profile can be determined over the whole diameter. In the case of a small pipe system 4 the voltage generating means 5, 6 and measuring means 8, 9 can also be accommodated as integrated component of these narrower pipes .

In another particularly suitable embodiment of the apparatus the voltage generating means 5, 6 and measuring means 8, 9 are arranged on a carrier 12. This carrier 12 with voltage generating means 5, 6 and measuring means 8 , 9 arranged thereon can for instance be placed parallel to the flow direction 9 in a flowing liquid, wherein the electrical impedance can be measured (see figure 4B) . The electrical field lines 13 will run more or less parallel to the average flow direction of the liquid for examination. By generating an alternating current electrical field with frequencies between 1 kHz and 5000 kHz it will be possible to determine the impedance of a biological liquid between two points in this liquid. Such an embodiment of the apparatus has the advantage that it can be used at different locations inside a pipe system which might be kilometres in length. In this case a constant flow speed or a corresponding flow profile is preferably also known, since the shear rate itself determines the viscosity to a significant extent, so that knowledge of this factor can provide insight into the viscosity properties of the liquid for examination. Such a carrier can also be provided with means for measuring the temperature 14, such as for instance a thermometer, built in for permanent determining of the temperature in the flowing liquid.

The voltage generating means 5, 6 preferably comprise at least one set of voltage electrodes 5, 6 connected to an alternating current source. An alternating current electrical field can hereby be applied in simple manner between two points in the liquid.

For the purpose of determining the impedance of the biological liquid between the two points in simple manner, the measuring means preferably comprise at least one set of measuring electrodes connectable to the recording device.

In a preferred embodiment of the apparatus the electrodes are circular and made from an efficiently conducting material, preferably platinum. In order to ensure a homogeneous electrical field, the distance between the electrodes is chosen such that it corresponds to at least twice the diameter of the tube through which the biological liquid flows. By means of generating an alternating current with frequencies IS3 _-__ «__.

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Claims

1. Method for determining at least one property of a flowing biological liquid, comprising of:

- generating an alternating current electrical field at a determined frequency in the biological liquid for a determined time;

- measuring during this determined time a measurement signal of the electrical impedance between at least two points in the biological liquid; and

- comparing the measurement signal with a predetermined relation between the measured impedance and the property of the liquid, wherein the biological liquid is not blood.

2. Method as claimed in claim 1, characterized in that the method further comprises of determining the temperature of the biological liquid during the impedance measurement, wherein the measuring signal is compared to a predetermined relation between the measured impedance, the temperature and the property of the liquid.

3. Method as claimed in claim 1 or 2 , characterized in that the biological liquid comprises oil .

4. Method as claimed in claim 1, 2 or 3 , characterized in that the property of the biological liquid comprises the viscosity of the liquid.

5. Method as claimed in claim 1, 2 or 3 , characterized in that the property of the biological liquid comprises the degree of purity of the liquid.

6. Method as claimed in any of the claims 1-5, characterized in that the determined frequency of the alternating current lies between 1 and 5000 kHz.

7. Apparatus for determining at least one property of a biological liquid, comprising:

- a tube for receiving a flow of biological liquid;

- means for generating an alternating current electrical field with a determined frequency in the biological liquid for a determined time; - means for measuring the electrical impedance between at least two points in the biological liquid; and

- a recording device connectable to the measuring means for recording the measured electrical impedance and/or impedance change in the biological liquid.

8. Apparatus as claimed in claim 7, characterized in that the apparatus further comprises means for measuring the temperature of the biological liquid.

9. Apparatus as claimed in claim 7 or 8, characterized in that the biological liquid comprises oil . .

10. Apparatus as claimed in claim 7, 8 or 9, characterized in that the apparatus further comprises a tube for transporting the biological liquid in which the voltage generating means and the measuring means are arranged.

11. Apparatus as claimed in claim 10, characterized in that the tube has a high electrical resistance.

12. Apparatus as claimed in claim 10 or 11, characterized in that the length of the tube corresponds to at least twelve times the diameter thereof.

13. Apparatus as claimed in claim 7, 8 or 9, characterized in that the voltage generating means and measuring means are arranged on a carrier.

14. Apparatus as claimed in any of the claims 7-13, characterized in that the voltage generating means comprise at least one set of voltage electrodes connected to an alternating current source.

15. Apparatus as claimed in any of the claims 7-14, characterized in that the measuring means comprise at least one set of measuring electrodes connectable to the recording device .

16. Apparatus as claimed in claim 14 or 15, characterized in that the electrodes are circular electrodes.

17. Apparatus as claimed in claim 14, 15 or 16, characterized in that the electrodes are platinum electrodes . N> ._____. _A o cn o n

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