Classifications

• • 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
  • G01N33/491—Blood by separating the blood components
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
  • G01N15/04—Investigating sedimentation of particle suspensions
  • G01N15/05—Investigating sedimentation of particle suspensions in blood

Definitions

• This invention concerns determination of the erythrocyte sedimentation rate, ESR, using an empirical relationship bet ⁇ ween the ESR value and certain electrically measured quanti- ties of the blood sample the ESR value of which is sought. Determination of the ESR value is a common diagnostic step. Usually, the ESR value is determined by first aspirat ⁇ ing an anticoagulated sample of the patient's blood into a narrow transparent tube so that the tube is filled to a pre- determined height, and then leaving the sample undisturbed for a certain time, typically one hour, whereupon the height of the more or less colourless supernatant column of blood plasma formed as a result of the sedimentation of the red blood cells is measured. The ESR value . ' equal to the height of this column in millimetres if the segmentation time is one hour.
• the rather long time required to arrive at the ESR value using this technique is a serious drawback, and the object of this invention is to render possible a rapid determination of the ESR value using only a small volume of blood.
• an apparatus for determining the ESR value of a sample of blood which has the characterising features set forth in the independent claim.
• the dependent claims recite features of preferred embodiments of the apparatus.
• Fig. 1 is a diagrammatic view of a first embodiment which incorporates a particle counter used for determining the haematocrit of the blood;
• Fig. 2 is a diagrammatic view of a second embodiment in which the haematocrit is determined from the impedance of the blood;
• Fig. 3 is a diagrammatic view showing a modification of the embodiment shown in Fig. 2.
• a tube 2 which extends into the sample in the test tube 1 is connected to a measuring cell 3 provided with four electrodes, two outer electrodes 4 and two inner elec- trodes 5 positioned between the outer electrodes.
• blood is aspirated from the test tube 1 into the measuring cell and a current is passed through the blood in the measuring cell 3 by way of the outer electrodes 4.
• the voltage then produced between the two inner electrodes 5 is measured, and circuitry generally designated 6 determines the electrical impedance of the blood in accordance with well- known techniques.
• the current may be fed to the outer elec ⁇ trodes 4 at three different frequencies (the highest of which should be many times higher than the lowest) ; this permits simultaneous determination of the capacitance C of the blood and the resistance R of the blood plasma and at the same eli ⁇ minates errors due to the interior resistance of the erythro- cytes.
• a further possibility is to use known methods involv- ing only two frequencies and a measurement of phase shift in order to determine C and R.
• the blood is transported through the tube 2 and the mea ⁇ suring cell 3 by means of a pump 7.
• Another pump 8 feeds a liquid diluent from a reservoir 9 into the tube downstream of the measuring cell 3 to dilute the blood before the blood is passed through a very narrow and short passage 10 which forms part of an electronic blood cell counter of a well-known type.
• This blood cell counter comprises a pair of electrodes 11 which are positioned on opposite sides of the passage 10 and connected with circuitry 12 for counting the erythrocytes and determining the haematocrit of the blood.
• Determination of the ESR value of the blood is effected by means of circuitry 15 using an empirical relationship of the kind described below.
• a display 16 indicates the deter ⁇ mined ESR value.
• the circuitry 16 processes the inputs recei ⁇ ved from the impedance determination circuitry 6, the haema ⁇ tocrit determination circuitry 12 and the temperature deter ⁇ mination circuitry 14.
• the quantity is not very critical but the volume of added diluent should not exceed the volume of the undiluted blood sample.
• a preferred ratio of the volume of diluent to the volume of undiluted blood is 1/4 to 1/2 (the volume of anti ⁇ coagulant is included in the volume of diluent) .
• diluent to the blood may be effected from the diluent reservoir 9 by means of the pump 8.
• a separate diluent pump may be provided as described below.
• the addition of a small quantity of diluent is advanta ⁇ geous in that it inhibits certain saturation effects which have been found to occur with undiluted blood and affect the precision of the determination for high ESR values. It is important that only a small amount of diluent is added, be ⁇ cause the addition of a diluent also has been found to impose requirements for an increased accuracy of the ESR determina ⁇ tion circuitry 15. The dilution can be dispensed with if ESR values in the high range need not be determined very accura ⁇ tely.
• a diluent of low electrical conductivity such as an aqueous solution of glycine (monoaminoacetic acid) .
• the diluent should be isotonic so that any change of volume of the erythrocytes is avoided, or the determination of the haematocrit should be carried out on undiluted blood.
• the portion of the blood sample used for de- termining the haematocrit need not pass through the measuring cell 3; this portion of the blood may be fed to the cell counter through a separate line.
• a separate double pump 23 is provided to draw a precisely measured volume of blood from the test tube 1 through a narrow tube 22 and a precisely measured volume of diluent from a diluent reservoir 24 and to feed the blood and the diluent to a vessel 25 in which a thorough mixing is effected by means a suitable mixing device, not shown.
• pump 7 draws the diluted blood through tube 2 into the measuring cell 3 which is provided with a pair of outer electrodes 4 and a pair of inner electrodes 5. These electrodes are con ⁇ nected to impedance determination circuitry 6 which feeds its output to ESR determination circuitry 15. The latter also re- ceives the output of temperature measuring circuitry 14 and drives display 16.
• Fig. 3 illustrates a modification of the means for pro ⁇ viding a diluted sample to be drawn into measuring cell 3. Apart from this modification, the embodiment of Fig. 3 is identical with that shown in Fig. 2.
• the blood sample is taken from the patient into a special cylindrical test tube 36 having a closure 37 through which a hollow needle may be passed.
• the test tube 36 is filled with a predeter- mined volume of diluent and an anticoagulant.
• the test tube 36 is positioned in a holder 38 associated with a level indicator comprising a light source 39 and an array of photosensitive elements 40 on a scale 41.
• a computing circuit 42 connected to the level indicator 39-41 determines the total volume of the diluted sample in the test tube 36 and the degree of dilution.
• the output of circuit 42 is fed to ESR determination circuitry 15 (not shown in Fig. 3, see instead Fig. 2).
• a sealed test tube w ich is pre-filled with a predeter ⁇ mined volume of diluent (including an anticoagulant) and the interior of which is under a partial vacuum.
• diluent including an anticoagulant
• the diluted blood in the test tube 36 is fed to the mea ⁇ suring cell through a hollow needle 43 and tube 2.
• the haematocrit of the blood is determined from impedance measu ⁇ rements by means of the electrodes 4 and 5, and as in the embodiment of Fig. 1 the ESR value is determined using an empirical relationship. A number of examples of relatio "hips for use in determining the ESR value will be given herein ⁇ after.
• the determination as described herein ⁇ after comprises three steps: (1) correction for varying sample temperature, (2) determination of the haematocrit, and (3) determination of the ESR value. Temperature correction of the measured impedances can be accomplished using the empirical formula
• Z 0 is the normalised value of a certain impedance value Z t measured at temperature t in relation to a certain reference temperature t 0 for which the following empirical formulas have been established.
• Constant c is a constant for the temperature dependency of the impedances; this dependency varies slightly with the frequency of the current.
• the haematocrit H can be measured by means of a cell counter as in the embodiment of Fig. 1.
• the haematocrit H expressed as a volume percentage, is calculated using an empirical relationship which includes resistances measured at different frequencies and ratios of these resistances, such as the following relationship which includes the ratios rj and r 2 :
• R lf R 2 and R 3 are the resistances of blood anticoagulated with EDTA, as determined at frequencies of 100 kHz, 800 kHz and 1200 kHz.
• a rough ESR value can be calculated from the following empirical relationship
• C is the capacitance as measured at the second point in time
• the apparatus of Fig. 2 includes or is associated with a cell counter supplying the number of at least one type of cells in the blood, such as the number of white cells and/or the number of erythrocytes
• the ESR value can be calculated using a relationship of the following type
• B is the number of erythrocytes per 10 "12 litre of blood
• constant c 20 -0.078
• constant c 21 0.084
• constant c 22 -0.463
• constant c 23 l.973
• constant c 24 -0.0108
• constant c 25 -o.267
• constant c 26 1.974
• constant c 27 -11.03
• Determination of the ESR value using the method and the apparatus according to the invention requires only a relati ⁇ vely small volume of the sample of blood, 1 ml or less.

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• Health & Medical Sciences (AREA)
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• Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Hematology (AREA)
• Biomedical Technology (AREA)
• Physics & Mathematics (AREA)
• Immunology (AREA)
• Analytical Chemistry (AREA)
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• Medicinal Chemistry (AREA)
• Investigating Or Analysing Biological Materials (AREA)
• Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)

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• 1994
  • 1994-05-11 SE SE9401646A patent/SE507563C2/sv not_active IP Right Cessation
  • 1994-11-15 EP EP95901660A patent/EP0729569A1/en not_active Withdrawn
  • 1994-11-15 JP JP7514389A patent/JPH09505146A/ja active Pending
  • 1994-11-15 WO PCT/SE1994/001075 patent/WO1995014224A1/en not_active Application Discontinuation
  • 1994-11-15 AU AU10807/95A patent/AU1080795A/en not_active Abandoned
  • 1994-11-15 CN CN 94194142 patent/CN1135258A/zh active Pending

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