CN1707242A - Method and device for determining viscosity - Google Patents
Method and device for determining viscosity Download PDFInfo
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- CN1707242A CN1707242A CN 200410099778 CN200410099778A CN1707242A CN 1707242 A CN1707242 A CN 1707242A CN 200410099778 CN200410099778 CN 200410099778 CN 200410099778 A CN200410099778 A CN 200410099778A CN 1707242 A CN1707242 A CN 1707242A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
- G01N11/10—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by moving a body within the material
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
- G01N11/10—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by moving a body within the material
- G01N11/16—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by moving a body within the material by measuring damping effect upon oscillatory body
- G01N11/162—Oscillations being torsional, e.g. produced by rotating bodies
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/4905—Determining clotting time of blood
Abstract
A process and a device for determining the viscosity of a fluid are proposed. Very simple and accurate determination is enabled in that the magnetic particles in the fluid are set into vibration by a magnetic field which varies over time. A measurement of the amplitude and/or phase of particle vibration is used to determine the viscosity or an associated quantity, such as the coagulation of blood or the glucose content.
Description
Technical field
The present invention relates to the particularly method and apparatus of the correlative of microfluid of a kind of definite viscosity or fluid or the magnetic particle in fluid, and the application of this method and apparatus.
Prior art
US 3,967, and 934A discloses the system and method for definite blood coagulating time.Testing tube with blood moves up and down, and the Metal Ball in the testing tube inner blood remains on the upright position by static magnetic field.When testing tube moved up and down, blood flowed around Metal Ball.When blood clotting (cohesion), the upright position skew of Metal Ball from determining.By this skew effect, grating work and it are as measuring setting time.This component costs is high and need moving component especially.This method is not suitable for microfluid, and the sample of promptly little volume is particularly under milliliter or littler scope.In addition, can not obtain the information of vaporus.
JP 8-178823A discloses measurement cohesive material method of viscosity and device.Small soft magnetic granules is as measuring piece, it by outer static magnetic field in cohesive material as moving in a direction in silicones or the acryl resin.With the sensor of magnetic resistance effect work, detect the arrival situation of motion magnetic particle and the movement velocity and the time of measuring definite viscosity by for example.The Measuring Time of carrying out for the measuring piece that only descends by gravity in addition is very little, about 2-5 minute.The shortcoming of this known method is could obtain significant measuring accuracy by carrying out test of many times in requisition for the magnetic particle that adds.This method expense is high and time-consuming.It is that the sample of little volume is particularly under milliliter or littler scope that its method is not suitable for microfluid.In addition, can not obtain the information of vaporus.
Summary of the invention
The object of the invention is to provide a kind of definite viscosity or fluid or the particulate method and apparatus of the correlative of microfluid particularly in fluid, and the application of this method and apparatus, can realize simple compact structure and accurately determine viscosity or relevant amount, can determine viscosity or relevant amount continuously especially.
The device of the method for above-mentioned purpose by claim 1, claim 24 or claim 48,49,50 application realize.Favourable further scheme is the theme of dependent claims.
Basic design of the present invention is, at least one magnetic particle vibrates by mM disodium hydrogen phosphate in fluid, make the particle independent pilot unmanaged flexibility in fluid that surrounds fully by fluid promptly in fluid or in the measurement chamber, not led by mechanical force, at least indirectly the amplitude and/or the phase place of measuring vibrations are determined viscosity or correlative such as Reynolds number and/or strouhal number etc. thus.Can determine viscosity or correlative simply exactly like this, can preferably not adopt the parts of mechanical motion, can determine viscosity continuously with high precision so that it is simple and compact for structure.In brief, particle vibration is called " vibration phase " with respect to the phase differential that changes (excitatory) magnetic field in time here.
Its viscosity needn't directly or definitely be determined.Usually enough as required is, only determine viscosity relatively or determine with viscosity on function, particularly have definite relation or with viscosity relevant amount.
Notion among the present invention " viscosity " in a narrow sense is interpreted as the particularly possibility that meets with stresses of liquid of the interior friction of fluid or fluid when distortion, and broadly " viscosity " or correlative are interpreted as especially the bonding by composition or analog or rise big, the change of possible non-uniform flow bulk properties, and/or for example be interpreted as by the atom on particle or the analog or the gathering or the separation of molecule the particularly change of its size, magnetic moment or motility or particle vibration damping or other characteristic of the flow characteristics of particle in the fluid.
Method and apparatus of the present invention can be used in particular for non-therapeutic purposes and determine the coagulability of blood and blood plasma (coherency), determine the atom on the magnetic particle or gathering or separation or definite concentration of glucose of molecule, wherein determine for example by the barrier film that passes glucose fluid viscosity relevant with blood and that be correlated with concentration of glucose.
Description of drawings
The preferred embodiment of Miao Shuing provides other advantage of the present invention, feature and viewpoint with reference to the accompanying drawings.Wherein:
Fig. 1 shows the block schematic diagram of first embodiment apparatus of the present invention;
Fig. 2 shows the variation magnetic field and to the signal phase diagram of magnetic particle acting force;
Fig. 3 shows the block schematic diagram of second embodiment apparatus of the present invention;
Fig. 4 shows the schematic section of the 3rd embodiment apparatus of the present invention;
Fig. 5 shows the synoptic diagram of the 4th embodiment apparatus of the present invention.
Embodiment
Identical or similar parts adopt identical Reference numeral in the accompanying drawing, and corresponding or similar characteristic and advantage no longer are repeated in this description.
In non-uniform magnetic-field, magnetic dipole is subjected to along the effect of field gradient power.Thus, the magnetic particle in the fluid is by the effect campaign of non-uniform magnetic-field.Because magnetic field is along with the time changes, the magnetic particle vibrates as required.Method and apparatus of the present invention is based on this principle.
According to the present invention, to measure the amplitude and/or the vibration phase of particle at least indirectly, this depends on the decay of particle vibration and represents the size of viscosity or other characteristic of fluid and/or particle thus.To this, in the above-mentioned size of broadly determining viscosity or relative fluid or particle according to amplitude and/or phase place.
Its viscosity needn't be directly or is definitely determined or expression.Usually this be enough to determine viscosity relatively or determine with viscosity function particularly on the definite relation or with viscosity relevant amount.
Fig. 1 shows the synoptic diagram according to first embodiment apparatus of the present invention, is used for determining the amount of viscosity or relative fluid 2.
The volume of measuring fluid is very little, preferred only in μ l scope.Particularly so-called microfluid.
Preferred 3 on magnetic particle joins in required fluid 2 measurement volumes or in certain spatial dimension or in the local measurement scope, like this, the amount of required magnetic particle 3 is less, and particle 3 can be distributed in the whole fluid 2.
Also can use in principle other magnetic particularly permanent magnetism or ferromagnetic particle 3.
When its particle 3 preferably was spherical at least substantially, the mean diameter of particle 3 was preferably 20nm to 1000 μ m, was about 100nm to 500 μ m especially, and especially preferably was about 0.5 μ m to 100 μ m.
Preferred particle 3 is of similar shape and/or size or identical mean diameter at least.
In the embodiment shown, giving the control device 7 of two oscillators that 5 configurations of two coils have preferred adjusting amplitude, frequency, phase place and/or deviation especially or function generator and be configured in conversion amplifier 8 between them in case of necessity, is 90 ° magnetic field thereby produce periodic preferred sine-shaped phase differential by coil 5.
The magnetic field superposition that produces by coil 5 become change in time to the non-uniform magnetic-field 6 of particle 3 generation effects alternating magnetic field preferably.By mM disodium hydrogen phosphate 6, make i.e. the moving back and forth of particle 3 vibration.
Its device 1 is preferred to be constituted or control produces magnetic field 6 like this coil or coil 5 like this, makes particle 3 carry out the passive preferably basic at least sine-shaped vibration that is.
This device 1 comprises sensing device 9 and measurement mechanism 10, to detect amplitude and/or the phase place that particle 3 moves and promptly vibrates and measure this vibration in fluid 2.
In an illustrated embodiment, its sensing device 9 has the particularly a plurality of coils 11 of a measurement coil 11 at least.Particularly be provided with three altogether and measure coil 11, they are preferably opposite end and opposite coiling that is arranged on coil 5 over the ground, are used to compensate the magnetic field that is produced by coil 5, thus, are easier to detect or measure the vibration of particle 3.
In the embodiment shown, Zhong Jian measurement coil 11 be used for two coils to promptly Fig. 1 not only be used for right coil to but also to be used for left coil right.Saved the 4th like this and measured coil 11.But also can be provided with the 4th in principle and measure coil 11, independently to measure coil right to form two.
By coil 11 measuring vibrations the time, particularly measure induced voltage, it depends on frequency, amplitude and the magnetic moment of particle 3.
As shown in Figure 1, the signal of measurement coil 11 directly or as required is transported to measurement mechanism 10 through prime amplifier 12.This prime amplifier 12 for example can be used to measure the electronic compensating of coil 11 and/or impedance matching etc.
This measurement mechanism 10 detects or measures amplitude and/or the phase place that particle 3 vibrates in fluid 2.Particularly in order to determine phase place, to say that control device 7 is delivered to measurement mechanism 10 with synchronous or reference signal as required, as representing by the respective lines in embodiment illustrated in fig. 1 with respect to the exciting field that particle 3 is acted on or the phase shifts in magnetic field 6 exactly.
Measurement mechanism 10 is especially according to so-called method for synchronous work and preferably have so-called synchronizing amplifier.
Can replace or additional preferred method for synchronous, its measurement mechanism 10 also can be measured amplitude and/or the phase place that particle 3 vibrates in other mode in fluid 2.
For example can the absolute measurement amplitude according to corresponding calibration, but also can relative measurement, for example Measuring Time curve or time dependent amplitude.This time curve represents for example to solidify advance degree when blood solidifies as fluid 2.
The amplitude of particle vibration and phase place depend on damping and depend on viscosity thus.According to measured amplitude and/or phase place, determine the correlative of viscosity and/or fluid 2 and/or particle 3.This is especially by particularly computing machine or similar device realization of apparatus for evaluating 13.
Viscosity or relevant amount preferably can be shown and/or by unshowned interface output, for example further handle.
Its sensing device 9 can replenish or alternatively have other magnetic and/or electric transducer, measures coil 11 to substitute, and detects particle 3 vibrations.For example can use GMR (large-scale magnetic resistance), TMR (tunnel type magnetic resistance), AMR (anisotropic magnetoresistive) or magnetic resistance, magnetoimpedance spare, Hall sensor or similarity piece as sensor.Particularly according to the vibration of magnetic effect, effect or Characteristics Detection particle 3.For example for so-called XMR-sensor, as the GMR-sensor or for Hall sensor, can determine vibration amplitude by measuring leakage field.But sensor in case of necessity can also be by sound, electric capacity or induction work.
In first embodiment, it is sinusoidal magnetic field periodically especially at least substantially that two coils 5 preferably produce respectively, and it is 90 ° that their effects by control device 7 preferably produce phase shifts, particularly phase differential.The synoptic diagram of Fig. 2 has provided the rough approximation of mid point between two coils 5, promptly shows the time curve in two magnetic fields that produced by coil 5, they by line 14 and 15 by being that 1 substandard amplitude is represented by value.
Two magnetic fields 5 that two coils 5 produce are superimposed as the time dependent non-uniform magnetic-field 6 to particle 3 effects, and it is by 16 expressions of the line among Fig. 2.
It should be noted that, be that the particle 3 of Super permanent magnet is subjected to all the time and polarizes at least be the effect of the irrelevant high-intensity magnetic field direction power of spatial field gradient direction.This can explain like this that the magnetic moment of Super permanent magnet particle 3 makes them towards (by force) coil 5 tractions that produce magnetic field 6 all the time like this facing to the direction in magnetic field 6 at least.
Leak in the space in magnetic field 6 between line 17 expression two coils 5 among Fig. 2, wherein the position change of particle 3 since its oscillating action promptly since vibration amplitude very I to ignore.Two curves 16 and 17 doubly take advantage of (Multiplikation) obtain line 18, and its expression is used for the size to particle 3 acting forces that produced by magnetic field 6.To this, be noted that the process that acts on particle 3 power has magnetic field 6 frequencies that double.Correspondingly, in the first embodiment, the magnet excitation frequency vibration of particle 3 to double.
Because according to the effect that doubles vibration frequency that changes or change the particle 3 in magnetic field 6 in time, particularly in preferred method for synchronous, the undesired signal that is produced by (difference) magnetic susceptibility is hidden from view at least continuously especially, and this is because this undesired signal does not present and adds overtones band, and only presents magnet excitation frequency.Particle 3 vibration signals that produced and double the measuring-signal of excitatory method for synchronous based on the signal of particle magnetic susceptibility measuring-signal, particularly assessment as measurement mechanism 10.
Thus, the measurement of particle amplitude and/or phase place (measuring-signal ∝ amplitude-frequency/particle vibration distance 4) simply is ratio.Its result is illustrated in the amount under the particle vibration damping and described meaning in the fluid 2.Under corresponding measurement and/or comparing and measuring of carrying out simultaneously, correspondingly determine for the viscosity of explaining meaning and/or the correlative of fluid 2 or particle 3 according to amplitude or phase place.
In the first embodiment, the alternating field of having only magnetic field 6 to produce substantially acts on the magnetic particle 3.This particularly realizes like this, magnetic particle 3 fluid 2 enough evenly and/or relevant measured zone enough concentrate and/or particle 3 quilt is concentrated or maintenance by the heterogeneity in measured zone magnetic field 6 is enough big.
Opposite is if special static magnetic field acts on particle 3, for example in order to concentrate in measured zone and/or the direction of definite magnetic moment, influence and determine in case of necessity the magnetic moment of particle, making can be according to changing the overtones band that adds that the magnetic field 6 that changes is created in particle 3 vibrations described in first embodiment, because magnetic moment is free not directed with respect to magnetic field 6 in time.
Fig. 3 shows second embodiment of apparatus of the present invention 1.Below, the difference with first embodiment is only described.The advantage of others is identical with feature or similar at least.
Only be provided with one and produce the coil 5 of variation magnetic field 6 in time.
But two coils 5 also can be set, and they preferably are made of the Helmholtz coils 5 of reversed polarity parallel connection.The preferred oppositely coiling of these coils makes that the arctic or the South Pole of coil 5 is directed each other when sine is excitatory.In order to produce mM disodium hydrogen phosphate 6, because oppositely the effect of the coil 5 of coiling has only an oscillator or function generator to get final product.
For this second embodiment, particle vibration detects by measuring coil 11 and realizes.Their preferred compensation mutually make that particularly its synchronizing amplifier or similar device do not produce signal in measurement mechanism 10 in the ideal case for the magnetic field 6 of coil 5.
In this second embodiment, one or two preferably only is set measures coil 11.In order to compensate alternating field 6, measure coil 11 and preferably be symmetrical in coil 5 settings, wherein measure coil 11 and radially surround measurement chamber 4.
Measure degenerative alternating field impedance bridge in the loop in order to replenish or to replace prime amplifier 12, can being connected, measure sensitivity to improve.
In second embodiment, give the non-homogeneous alternating magnetic field 6 preferred stack one time-independent high-intensity magnetic fields 19 of coil 5.This magnetic field 19 or form or form by unshowned permanent magnet or ring-shaped magnet by the coil 20 that electromagnet passing through as shown in Figure 3 only has a circle or a multi-turn.
This high-intensity magnetic field 19 is on the face of the strongest coil 20 and on this face or coil 20 zones or replace the additional magnet zone aggregate particles 3 of using.Also might be pulled outwardly on 4 walls of measurement chamber from the middle part of measuring chamber 4 by coil 5 by coil 20 for fear of particle 3, measure chamber 4 an antimagnetic shield spare 21 is set, it is arranged between particle 3 and the coil 5,20.
In the embodiment shown, this shielding part 21 is the sky tubular especially.It surrounds in case of necessity fully measures chamber 4.This antimagnetic shield spare 21 also can directly form or form measurement chamber 4 by the wall of measuring chamber 4 when needing.
This antimagnetic shield spare 21 make particle 3 near the time be subjected to repulsive force by shielding part 21 repulsions.Like this can so that particle 3 assemble or remain on the equilibrium position and in addition in above-mentioned mode in the embodiment shown along four-headed arrow 6 forced vibrations.This device 1 also has to make particle 3 assemble by magnetic especially or remains on the measure that area of space is preferably measured the local measurement zone in the chamber 4.This measure realizes by magnetic field 6 when needed, also may adopt alternate manner to realize, regulate at least or control particle 3 especially like this, make particle 3 or a plurality of particle 3 remain on regional area in the period of enough measuring at least and preferably remain on measured zone according to the measuring position.
Because the effect in magnetic field 19 has promptly been determined the direction of particle 3 magnetic moments in the chamber in the direction of non-uniform magnetic-field 19.The vibration that weak alternating magnetic field 6 only produces the particle 3 of same frequency thus.Doubling frequency in first embodiment here can not appear.
The undesired signal that produces by the magnetic susceptibility effect is passed through the simple excitatory adjusting in magnetic field 6 especially.Because particle 3 is with identical frequency vibration, the phase difference detection according to magnet excitation frequency can mainly only or be the most simply passed through in the vibration of particle 3.
Antimagnetic shield spare 21 equally preferably can be used for first embodiment, does not describe but be in the simplification purpose.
Fig. 4 shows the schematic vertical cross-section figure of apparatus of the present invention 1 the 3rd embodiment.Below, the difference with first and/or second embodiment is only described.The advantage of others, feature is identical with technical possible mode or similar at least.
In the 3rd embodiment, measure chamber 4 and preferably be formation on the sample bearing 22 of plate shape.This sample bearing 22 preferably is made of plastics, and forms corresponding hole thereon.For example this is relevant with test bar etc., and it is used in particular for chemistry and/or biological diagnosis or microfluid check.
This is measured chamber 4 and preferably forms at the principal spread direction perpendicular to sample bearing 22 plate faces.The axis of coil 5 and mM disodium hydrogen phosphate 6 preferred directions with measurement chamber 4 are identical, promptly perpendicular to the plate face of sample bearing 22.
The vibration of magnetic particle 3 is preferred to be carried out on perpendicular to the plate face of sample bearing 22 or face side at least substantially.
According to unshowned modification, blood or blood plasma 23 can be directly as fluid 2 and for example direct input measurement chambeies 4.In this case, measure chamber 4 and preferably have magnetic particle 3 and particularly coagulator.
After importing blood or blood plasma, magnetic particle 3 in blood or blood plasma 23 and/or especially accumulates in measured zone by the static magnetic field 19 of coil 20 by Distribution of Magnetic Field especially, can also being mixed or mixing by the unshowned coagulator of the vibration realizing of particle 3 and blood or blood plasma 23.
As mentioned above, especially determine viscosity or relevant size and be illustrated in the condense amount of (cohesion) of blood in the chamber 4 or blood plasma of measuring especially according to first or second embodiment.The device 1 of this modification can directly be measured or the coherency of definite blood or blood plasma 23.
In the embodiment of Fig. 4, device 1 or sample body 22 also have the barrier film 24 that can pass glucose.Special this device 1 can also be accepted interstitial liquid where necessary to substitute blood or blood plasma 23.2 pairs of glucose of fluid sensitivity are the content change of the viscosity of fluid 2 according to glucose.For example, fluid 2 contains macromolecule dextrin, the concanavalin affine feelings agent as glucose, denaturant and/or other glycan molecule.
The fluid 2 that carries out the glucose exchange through barrier film 24 and blood or blood plasma 23 or interstitial liquid for example pumps into by unshowned pump or device and measures chamber 4 or by measuring chamber 4 and through barrier film 24 circulations.
According to first or second embodiment, in measuring chamber 4, determine the amount of viscosity or associated fluid 2 and determine glucose content thus especially.
As required, when measuring magnetic particle 3 vibration amplitudes and/or phase place, continue input or circulation fluid to glucose-sensitive.Identical or at least substantially evenly flow through consistently when measuring chamber 4 at fluid 2, only enable coil 5 as required, produce mM disodium hydrogen phosphate 6, make magnetic particle 3 measure chamber 4 or the vibration of desirable measured zone, thereby determine viscosity and glucose content by flowing and acting on thereon being superimposed upon of power.
Fig. 5 shows the 4th embodiment synoptic diagram of apparatus of the present invention 1.Below, the difference with above-mentioned embodiment is only described.The advantage of others is identical with feature or similar at least.
Producing in time, the coil 5 of variation magnetic field 6 surrounds end regions or joins with the end of measuring chamber 4.
For variation magnetic field 6 and time-independent high-intensity magnetic field 19 stacks also are provided with coil 20.
In addition, static magnetic field 19 preferably forms between central region and/or coil 5, forms the heterogeneity or the decline of particle 3, makes them in this region clustering or maintenance.The coil 20 that increases is axially forming with very little structure and is only constituting by a circle where necessary.The magnetic field 19 that is produced by coil 20 is enough to make particle 3 to be drawn into its coil surface.
The magnetic field 6 that changes makes so-called relatively initial position of particle 3 or rest position vibrate.
In the 4th embodiment, antimagnetic shield spare 21 is directly formed by the wall of measuring chamber 4.
In the 4th embodiment, substitute the sensing device 9 of measuring coil 11 and have GMR 26 as sensor, detect the vibration of particle.Particularly only adopt a sensor or GMR 26, to detect the vibration of particle, because its resistance or measuring-signal are obviously along with the distance of particle 3 apart from GMR 26 changes and change according to controllable particle vibration thus.Then assess with above-mentioned embodiment or in other mode that is fit to.
According to a preferred modification of implementing, device 1 is controlled particle 3 at least in the part or under resonance frequency.Like this, obtain big relatively particle 3 amplitudes under relatively little power consumption, this can measure amplitude and/or phase place more accurately.
According to particularly preferred enforcement modification, the frequency of variation magnetic field 6 is changed enduringly and/or controls or be adjusted to resonance frequency or has the minimum amplitude of particle 3 or the frequency of peak swing.
By changing the frequency of its variation magnetic field 6, determine amplitude and the phase place and the amount of acquiring change at least relatively.Determine the change of viscosity and/or particle properties thus.
Be other characteristic that the relation of particle vibration amplitude and/or phase place and variation magnetic field 6 frequencies is determined its size and particle 3 in case of necessity preferably according to resonance frequency and/or tuning curve.This especially can be at the known properties and/or the corresponding measurement of fluid 2.
Replaceable or additional is, by measuring amplitude and/or phase place and/or definite tuning curve of particle vibration, qualitatively with may guarantee qualitatively or the motility of definite particle 3 in fluid 2 and thus for example qualitatively with may determine on the particle 3 qualitatively or the gathering of the atom of particle 3 and molecule or disengaging situation.
Implement modification according to another, the particle 3 size differences that adopted, special particle 3 has two kinds of sizes at least.Preferably, preferably or continue and the amplitude and/or the phase place of particle vibration are measured in the different resonance frequencies of two particle size zone.
As from the foregoing, method and apparatus 1 of the present invention is generally suitable for measuring the particularly size of liquid or particle 3 of viscosity or relevant fluid 2, also can determine or detect the coagulability of blood or blood plasma 23 especially or detect glucose content.Method and apparatus 1 of the present invention is particularly suitable for microfluid system.
Notion among aforesaid the present invention " viscosity " in a narrow sense is interpreted as the interior friction of fluid 2 or the possibility that fluid 2 meets with stresses when distortion, and broadly " viscosity " is interpreted as especially the bonding by composition or analog or rises big or dissociate, the change of possible heterogeneous fluid 2 characteristics, and/or for example be interpreted as the gathering by atom on the particle 3 or molecule or separate formation or decomposition or analogue, the flow characteristics of the particle 3 in the fluid 2 or the change of other characteristic as complex compound.Method and apparatus 1 of the present invention can be determined the viscosity on this meaning.
What replace or add is for example can determine Reynolds number and/or strouhal number etc. by method and apparatus 1 of the present invention.
Method and apparatus 1 of the present invention is particularly suitable for detecting or measuring heterogeneous fluid 2.
Particularly, device 1 is used for microfluid to be measured, and the volume in its measurement chamber 4 is 1ml to the maximum, preferably is 500 μ l to the maximum, is 100 μ l especially to the maximum, or is about 0.5-20 μ l.
It should be noted that each feature of described embodiment and other modification in technical scheme and claim combination in any each other.
Claims (50)
1, a kind of definite fluid (2) method of particulate (3) amount in the viscosity of microfluid or relative fluid (2) amount or the fluid (2) particularly, wherein the magnetic particle (3) in the fluid (2) moves by non-uniform magnetic-field (6) at least, wherein particle (3) vibrates by mM disodium hydrogen phosphate (6) and moves back and forth, particle (3) keeps by magnetic or accumulates in area of space in the fluid (2), wherein amplitude and/or the phase place by the Magnetic Measurement vibration and determine the damping of viscosity or correlative or particle vibration thus.
2. method as claimed in claim 1 is characterized in that: mM disodium hydrogen phosphate (6) is and is the sinusoidal variation periodically especially.
3. as the method for claim 1 or 2, it is characterized in that: mM disodium hydrogen phosphate (6) is by a coil (5) or by preferably forming at direction of vibration two coils (5) at interval.
4, method as claimed in claim 3 is characterized in that: the magnetic field of coil (5) is sinusoidal periodically especially and preferably changes with 90 ° phase differential.
5, as the method for claim 3 or 4, it is characterized in that: particle (3) is by the frequency vibration that doubles in coil (5) magnetic field.
6, as the method for one of above-mentioned claim, it is characterized in that: particle (3) is by the frequency vibration that doubles of variation magnetic field (6) in time.
7, as the method for one of claim 1-4, it is characterized in that: the direction of motion orientation that the magnetic moment of particle (3) is preferably vibrating in the direction of vibration by static magnetic field (19).
8, as the method for one of above-mentioned claim, it is characterized in that: particle (3) is particularly assembled in measured zone and/or the mM disodium hydrogen phosphate (6) or is kept at the area of space of fluid (2) by static magnetic field (19).
9, as the method for claim 7 or 8, it is characterized in that: static magnetic field (19) magnetic field intensity ratio is being eager to excel of variation magnetic field (6) in time.
10, as the method for one of above-mentioned claim, it is characterized in that: particle (3) is stabilized in the area of space in the fluid (2) particularly in the measured zone by antimagnetic shield spare (21).
11, as the method for one of above-mentioned claim, it is characterized in that: in order to measure, fluid (2) is input in the measurement chamber (4) of containing particle (3), particularly a plurality of particles (3) vibrate in fluid (2) by variation magnetic field (6).
12, as the method for one of above-mentioned claim, it is characterized in that: particle (3) carries out forced vibration.
13, as the method for one of above-mentioned claim, it is characterized in that: its amplitude is 1mm to the maximum, is preferably 0.5mm, in particular for 0.1mm or littler.
14, as the method for one of above-mentioned claim, it is characterized in that: the frequency of mM disodium hydrogen phosphate (6) and/or amplitude and/or time change such Be Controlled or adjusting, and promptly feasible at least in the period of regulation, particle (3) vibration amplitude is greater than minimum value.
15, as the method for one of above-mentioned claim, it is characterized in that: the vibration of particle (3) detects by sensing device (9), and this sensing device comprises especially at least measures coil (11), magnetic resistance, magnetoimpedance spare, Hall sensor and/or other sensor.
16, as the method for one of above-mentioned claim, it is characterized in that: the amplitude and/or the phase place of vibration are measured by simultaneous techniques.
17, as the method for one of above-mentioned claim, it is characterized in that: the amplitude of vibration and/or phase place basis or definite with respect to variation magnetic field (6).
18, as the method for one of above-mentioned claim, it is characterized in that: have a plurality of particles (3) in the fluid (2) or vibrate.
19, as the method for one of above-mentioned claim, it is characterized in that: use and contain iron oxide, particularly magnetic iron ore or other ferritic super magnetic particle (3) and/or particle (3).
20, as the method for one of above-mentioned claim, it is characterized in that: the mean diameter of particle (3) is 20nm to 1000 μ m, preferably is about 100nm to 500 μ m, and especially preferably is about 0.5 μ m to 100 μ m.
21, as the method for one of above-mentioned claim, it is characterized in that: the proportion of particle (3) equals the proportion of fluid (2) or at least substantially greater than the proportion of fluid (2).
22, as the method for one of above-mentioned claim, it is characterized in that: be graininess, spherical and/or ellipticity particle (3) and/or particle (3) and have the shell that is made of plastics especially.
23, as the method for one of above-mentioned claim, it is characterized in that: fluid displacement is less than 1ml, preferably less than 100 μ l, especially less than 20 μ l.
24, the device (1) of particulate (3) amount in a kind of definite viscosity or relative fluid (2) amount or the fluid (2), comprise the measurement chamber (4) that holds fluid (2), produce the coil (5) of time dependent non-uniform magnetic-field (6), make the magnetic particle (3) that surrounds fully by fluid (2) at least in fluid (2), in fluid (2), vibrate by variation magnetic field (6), comprise also being used for sensing device (9) and/or the measurement mechanism (10) that magnetic detects particle vibration that measuring vibrations is determined the damping of amplitude and/or phase place or the measurement correlative or the particle vibration of viscosity.
25, as the device of claim 24, it is characterized in that: its device (1) is made of sample bearing (21), titer plate or test-strips.
26, as the device of claim 24 or 25, it is characterized in that: what be used for the device (1) of fluid (2) or measure chamber (4) holds volume less than 1ml, preferably less than 100 μ l, especially less than 20 μ l.
27, as the device of one of claim 24-26, it is characterized in that: device (1) constitutes like this, promptly makes mM disodium hydrogen phosphate (6) be particularly periodically that sinusoidal changes and/or its particle (3) carries out forced vibration.
28, as the device of one of claim 24-27, it is characterized in that: device (1) has a coil (5) or preferably at direction of vibration two coils (5) at interval, produces mM disodium hydrogen phosphate (6).
29, as the device of claim 28, it is characterized in that: its coil (5) is made of Helmholtz coils.
30, as the device of one of claim 24-29, it is characterized in that: device (1) has and produces the device (7), particularly two oscillators or function generator that phase differential particularly is 90 ° two magnetic fields, preferably regulates its amplitude, phase differential and/or skew.
31, as the device of one of claim 24-30, it is characterized in that: its device (1) has the coil (20) or the magnet of generation static magnetic field (19), makes the magnetic moment of particle (3) preferably directed and/or make particle (3) particularly assemble in the measured zone or keep at the area of space of fluid (2) in the direction of motion of vibration in the direction of vibration.
32, as the device of claim 31, it is characterized in that: static magnetic field (19) magnetic field intensity ratio is being eager to excel of variation magnetic field (6) in time.
33, as the device of one of claim 24-32, it is characterized in that: its device (1) has antimagnetic shield spare (21), assemble with particularly a plurality of particles of stable particle (3) (3) and/or the area of space in measuring chamber (4) or in fluid (2), preferable mask part (21) is arranged between particle (3) or a plurality of particle (3) and the coil (5,20).
34, as the device of one of claim 24-33, it is characterized in that: device (1) has the measurement chamber (4) that holds fluid (2) of containing preferred particle (3).
35, as the device of claim 34, it is characterized in that: it is measured chamber (4) and forms in preferably being the sample bearing (22) of plate shape.
36, as the device of claim 35, it is characterized in that: its device (1) constitutes like this, promptly makes vibration transverse to particularly perpendicular to the face side of sample bearing (22).
37, as the device of claim 35 or 36, it is characterized in that: its produce change in time and/or the coil (5) of static magnetic field (6,19) with respect to sample bearing (22) side regions or on its zone, be provided with.
38, as the device of one of claim 24-37, it is characterized in that: its device (1) constitutes like this, makes that promptly the amplitude of its particle vibration is 1mm to the maximum, is preferably 0.5mm, in particular for 0.1mm or littler.
39, as the device of one of claim 24-38, it is characterized in that: its device (1) has the preferred sensing device (9) of directly measuring particle vibration, and preferably its sensing device (9) has measurement coil (11), magnetic resistance, magnetoimpedance spare, Hall sensor and/or optical sensor at least.
40, as the device of one of claim 24-39, it is characterized in that: its device (1) has the particularly super magnetic particle (3) in measuring chamber (4) at least.
41, as the device of one of claim 24-40, it is characterized in that: the size of the magnetic particle that its device (1) has is 20nm to 1000 μ m, preferably is about 100nm to 500 μ m, and especially preferably is about 0.5 μ m to 100 μ m.
42, as the device of one of claim 24-41, it is characterized in that: its device (1) has the graininess of being, spherical and/or ellipticity particle (3) and/or magnetic particle (3), and it contains iron oxide, particularly magnetic iron ore or other ferrite.
43, as the device of one of claim 24-42, it is characterized in that: its device (1) comprises having the magnetic particle (3) that is made of plastics shell especially.
44, as the device of one of claim 24-43, it is characterized in that: the structure of its device (1) can be especially automatically by blood or the blood plasma (23) of capillary force absorption as fluid (2).
45, as the device of claim 34 and 44, it is characterized in that: it is measured chamber (4) and has magnetic particle or a plurality of magnetic particle (3) and coagulator, imports blood and blood plasma (23) back by determining its viscosity measurement or detecting its coagulability.
46, as the device of one of claim 24-45, it is characterized in that: the structure of device (1) can be implemented the method for one of claim 1-23.
47, as the device of one of claim 24-43, it is characterized in that: its device (1) comprises measurement chamber (4), the magnetic particle (3) of the fluid (2) that has glucose-sensitive and the barrier film (24) that passes glucose, to device (1) input blood or blood plasma (23) or interstitial liquid, blood or blood plasma (23) or interstitial liquid carry out the glucose displacement by barrier film (24) and fluid (2) to glucose-sensitive and by determining the viscosity measurement of the fluid (2) of glucose-sensitive or the content of the glucose of detection in blood or blood plasma (23) or interstitial liquid.
48, determine the application of viscosity method and apparatus (1), determine the coagulability of non-therapeutic purposes blood, wherein add magnetic particle (3) at least and add coagulator where necessary in blood, the device (1) of one of the method by one of claim 1-23 or claim 24-45 is determined viscosity and is determined the coagulability of blood thus.
49, determine the application of viscosity method and apparatus (1), determine that non-therapeutic purposes are to the concentration of glucose in the fluid (2) of glucose-sensitive, wherein in fluid (2), add magnetic particle (3) at least, determine viscosity and determine concentration of glucose thus by the method for one of claim 1-23 or the device (1) of one of claim 24-43 or 47.
50, determine the application of the method and apparatus (1) of the damping that particle (3) motility or particle (3) move in fluid (2), determine gathering or dissociating from the particle (3) on molecule particularly or the particle (3) of atom in fluid (2), at least magnetic particle (3) adds in the fluid (2), and the device (1) of one of the method by one of claim 1-23 or claim 24-47 is determined the motility of at least one particle (3) in the fluid (2), damping and/or changed and determine its gathering thus.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10359438.8 | 2003-12-17 | ||
| DE10359438 | 2003-12-17 | ||
| DE102004009089.0 | 2004-02-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1707242A true CN1707242A (en) | 2005-12-14 |
Family
ID=34683509
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410099778 Pending CN1707242A (en) | 2003-12-17 | 2004-12-17 | Method and device for determining viscosity |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1707242A (en) |
| DE (1) | DE102004009089A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102834722A (en) * | 2010-03-30 | 2012-12-19 | Ca卡西索股份公司 | Composition for the determination of coagulation characteristics of a test liquid |
| CN101842668B (en) * | 2007-06-25 | 2013-06-19 | 集成感应系统公司 | Microfluidic device and microtube therefor |
| CN105004633A (en) * | 2015-06-24 | 2015-10-28 | 广东工业大学 | Nanowire vertical array based fluid viscosity detection device and detection method |
| CN106053590A (en) * | 2016-07-20 | 2016-10-26 | 重庆鼎润医疗器械有限责任公司 | Testing device for magnetic suspension thrombus elasticity |
| CN107462628A (en) * | 2017-09-14 | 2017-12-12 | 重庆南方数控设备有限责任公司 | A kind of thrombus detection device for elasticity and detection method based on magnetic |
| CN113933532A (en) * | 2021-10-12 | 2022-01-14 | 中国人民解放军国防科技大学 | Device and method for measuring liquid flow velocity based on alternating magnetic field |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19735931C2 (en) * | 1997-08-08 | 2002-02-07 | Lerche Dietmar | Piston stroke pipette for volume metering and viscosity measurement |
| DE19745807C2 (en) * | 1997-10-16 | 2001-05-03 | Andreas Bausch | Magnetic ball microrheometer |
| DE10130727C2 (en) * | 2001-06-21 | 2003-09-18 | Mediquant Gmbh | Method and device for measuring micro-viscosity changes as an immunoassay |
-
2004
- 2004-02-25 DE DE102004009089A patent/DE102004009089A1/en not_active Ceased
- 2004-12-17 CN CN 200410099778 patent/CN1707242A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101842668B (en) * | 2007-06-25 | 2013-06-19 | 集成感应系统公司 | Microfluidic device and microtube therefor |
| CN102834722A (en) * | 2010-03-30 | 2012-12-19 | Ca卡西索股份公司 | Composition for the determination of coagulation characteristics of a test liquid |
| CN105004633A (en) * | 2015-06-24 | 2015-10-28 | 广东工业大学 | Nanowire vertical array based fluid viscosity detection device and detection method |
| CN105004633B (en) * | 2015-06-24 | 2018-02-13 | 广东工业大学 | Fluid viscosity detection means and detection method based on nano wire orthogonal array |
| CN106053590A (en) * | 2016-07-20 | 2016-10-26 | 重庆鼎润医疗器械有限责任公司 | Testing device for magnetic suspension thrombus elasticity |
| CN107462628A (en) * | 2017-09-14 | 2017-12-12 | 重庆南方数控设备有限责任公司 | A kind of thrombus detection device for elasticity and detection method based on magnetic |
| CN113933532A (en) * | 2021-10-12 | 2022-01-14 | 中国人民解放军国防科技大学 | Device and method for measuring liquid flow velocity based on alternating magnetic field |
Also Published As
| Publication number | Publication date |
|---|---|
| DE102004009089A1 (en) | 2005-07-21 |
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