[go: up one dir, main page]

WO2003019166A1 - Systeme et procede d'analyse de sang - Google Patents

Systeme et procede d'analyse de sang Download PDF

Info

Publication number
WO2003019166A1
WO2003019166A1 PCT/SE2002/001530 SE0201530W WO03019166A1 WO 2003019166 A1 WO2003019166 A1 WO 2003019166A1 SE 0201530 W SE0201530 W SE 0201530W WO 03019166 A1 WO03019166 A1 WO 03019166A1
Authority
WO
WIPO (PCT)
Prior art keywords
blood
haemoglobin
imaginary part
complex impedance
blood sample
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/SE2002/001530
Other languages
English (en)
Inventor
Ove Kastebo
Evald Koitsalu
Bertil Nilsson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
HAEMO WAVE AB
Original Assignee
HAEMO WAVE AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by HAEMO WAVE AB filed Critical HAEMO WAVE AB
Publication of WO2003019166A1 publication Critical patent/WO2003019166A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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

Definitions

  • the present invention relates to a system and a method for measuring the haemoglobin value in blood, more specifically to measurements in a closed system.
  • the conventional methods also involve high costs for disposable material and for handling waste of disposable material and chemicals.
  • Hematocrit values obtained by conventional analyses can most of the time be correlated to the haemoglobin value, but they fail when measuring blood from patients suffering from certain blood anomalies which may cause the blood to contain abnormally large or small blood cells.
  • the above prior arts methods involve measuring the impedance in blood.
  • WO/0009996 or its equivalent US-5 792 668 discloses specific determination of glucose in NaCl using a radio frequency spectral analysis method. This method comprises analysing the real and the imaginary part of the complex impedance in the radio frequency range up to 5 GHz.
  • the inventors have developed a technique primarily for determining the haemoglobin value in human blood in a closed system.
  • the present invention permits safe measurements of the haemoglobin value in blood, eliminating the user's exposure to chemicals and contagious blood.
  • the present invention also provides a system that presents high reliability in measurement results and that comprises a procedure of analysis that is so simple that only minimal laboratory experience is needed.
  • the aim of the invention is also to provide a method that does not involve addition of agents that degrade the blood samples, so that an analysed blood sample can be used for further analyses at for example a central laboratory.
  • Fig. 1 shows a scheme over the haemoglobin measuring system according to the present invention.
  • Fig. 2 shows a calibration curve that illustrates the measured reference haemoglobin values as a function of its corresponding imaginary part of the complex impedance (values deriving from measurements performed at 400 kHz) .
  • Fig. 3 shows a graph correlating the measured reference haemoglobin values and the haemoglobin values calculated using the inventive method (values originating from measurements of the imaginary part of the complex impedance performed at 400 kHz).
  • Fig. 4 shows a calibration curve, which shows the measured reference haemoglobin values as a function of its corresponding imaginaiy part of the complex impedance (values deriving from measurements performed at 500 kHz) .
  • Fig. 5 shows a graph correlating the measured reference haemoglobin values and the haemoglobin values calculated using the inventive method (values originating from measurements of the imaginary part of the complex impedance performed at 500 kHz).
  • Fig. 6 shows a calibration curve, which shows the measured reference haemoglobin values as a function of its corresponding imaginary part of the complex impedance (values deriving from measurements performed at 600 kHz).
  • Fig. 7 shows a graph correlating the measured reference haemoglobin values and the haemoglobin values calculated using the inventive method (values originating from measurements of the imaginary part of the complex impedance performed at 600 kHz).
  • Fig. 8 shows a calibration curve, which shows the measured reference haemoglobin values as a function of its corresponding imaginary part of the complex impedance (values deriving from measurements performed at 700 kHz).
  • Fig. 9 shows a graph correlating the measured reference haemoglobin values and the haemoglobin values calculated using the inventive method (values originating from measurements of the imaginary part of the complex impedance performed at 700 kHz).
  • Fig. 10 shows a calibration curve, which shows the measured reference haemoglobin values as a function of its corresponding imaginary part of the complex impedance (values deriving from measurements performed at 800 kHz) .
  • Fig. 11 shows a graph correlating the measured reference haemoglobin values and the haemoglobin values calculated using the inventive method (values originating from measurements of the imaginary part of the complex impedance performed at 800 kHz).
  • Fig. 12 shows a calibration curve, which shows the measured reference haemoglobin values as a function of its corresponding imaginary part of the complex impedance (values deriving from measurements performed at 900 kHz) .
  • Fig. 13 shows a graph correlating the measured reference haemoglobin values and the haemoglobin values calculated using the inventive method (values originating from measurements of the imaginary part of the complex impedance performed at 900 kHz).
  • the blood has an alternating current (A.C.) impedance constituted by a resistive and a reactive part, where the reactive part is constituted by the imaginary part of the complex impedance.
  • A.C. alternating current
  • a molecule is exposed to an alternating electrical field, e.g. between two electrodes constituting a capacitor, it is influenced such that a capacity change occurs.
  • the reactive part of the alternating current impedance of the blood is dependant on the amount of haemoglobin in the blood sample.
  • the electrical complex impedance of the blood sample can then be measured and the magnitude of the reactive part, i.e. the imaginary part of the complex impedance, can be correlated with the haemoglobin value in the blood.
  • Ackmann uses frequency intervals of 5 kHz to 1 MHz when analysing canine blood.
  • the present inventors have now identified frequency ranges where correlation between the haemoglobin value and the imaginary part of the complex impedance exists at least over a certain range in Hb concentration.
  • the system according to the present invention will be described with reference to Fig. 1, in which it is generally described with 1.
  • the system includes electrodes 204, an impedance meter 205, a display unit 210, a keyboard 211 and a memory (RAM/ROM) 212.
  • the impedance meter 205 comprises a signal generator 206 and a signal-processing unit 207.
  • the signal generator is capable of delivering an alternating current in a frequency range of 50 - 1200 kHz and measuring the impedance at one or more frequencies within the frequency range 50 - 1200, kHz.
  • the signal-processing unit 207 delivers an out-signal in analogue or digital form.
  • Fig. 1 there is also shown a sample tube 202 containing a blood sample 203.
  • a septum, a rubber cork or the like seals the tube.
  • a network analyser Rohde & Schwarz ZVC including some additional equipment belonging to it and a measuring device was used.
  • the vector network analyser that was used contained a signal generator 206 and a signal-processing unit 207 (see Fig. 1).
  • the electrodes are preferably made of a material that does not oxidise, has good conductivity and does not affect the blood sample, e.g. platinum. Said electrodes are arranged in a tightly sealed tube, preferably in an ordinary sample tube.
  • the system according to the invention uses only two electrodes 204, a measuring electrode and a reference electrode, but any number of electrodes can be employed in combination.
  • the electrodes 204 of the measuring device are introduced from below into the sealed blood sample tube 202 mounted upside-down, so that the electrodes penetrate the sealing of the blood sample tube and come into direct contact with the blood without first passing through air.
  • the signal generator 206 generates the electrical alternating field, which is applied to the blood sample 203 via the electrodes 204, the electrical alternating field preferably having a frequency within the range 50 - 1200 kHz.
  • the signal from the electrodes is amplified and filtered by the signal-processing unit 207, as a preparation for the transformation from analogue to digital form.
  • the signal-processing unit 207 processes the signal mathematically, whereby the reactive part of the signal is correlated with the haemoglobin value of the blood. This is performed within the frequency range 50 - 1200 kHz, and preferably at about 800 kHz, since the best correlation has been obtained at this frequency.
  • This information is subsequently prepared for presentation on the display unit 210.
  • a user can interact with the system, such as feeding it with patient information and data, in addition to controlling the system.
  • the signal-processing unit 207 is coupled to a memory 212, which preferably comprises a RAM and a ROM, wherein measurement data and other information can be saved and read.
  • the method according to the present invention is based on the discovery that within certain frequency intervals correlation exists between the haemoglobin value in blood within a certain concentration range and its imaginary part of the complex impedance.
  • a standard curve In order to perform the method according to the invention, a standard curve must be constructed. The imaginary part of the complex impedance is then measured and correlated with the haemoglobin value using the standard curve.
  • the standard curve is constructed by first centrifuging a reference blood (arbitrary blood sample) to obtain plasma. The plasma is then used to dilute the reference blood to five appropriate concentrations in haemoglobin. These concentrations lie in the range of normal human haemoglobin values. This interval is chosen because it matches the interval in which the ordinary measurement will be performed, but it is also chosen because linearity exists in this interval, at least for haemoglobin values of 80 to 180.
  • haemoglobin values in these samples are then measured with a reference instrument.
  • the respective corresponding imaginary parts of the complex impedance are determined at a frequency within the frequency range 50 - 1200 kHz using the above-mentioned network analyser (Rohde & Schwarz ZVC).
  • a ready-to-use system comprises a computer system having one or more of these equations stored in its memory unit. When performing the haemoglobin measurements the computer will then perform the correlation procedure.
  • the measurement of the imaginary part of the complex impedance in patient blood samples is performed by analysing blood samples from patients using the above- described measuring equipment (Rohde 85 Schwarz ZVC) at the same frequency within the frequency range 50 - 1200 kHz as mentioned above.
  • the reproducibility of the described method was determined by analysing several times each of a number of patient samples with the measuring equipment.
  • the variation expressed in %CV was 2,5 or lower at the level 80 - 135 g haemoglobin/1.
  • a reference blood sample (normal sample) was centrifuged and the plasma was separated in order to be used for dilution of the blood sample to 5 different levels of haemoglobin.
  • the diluted samples were analysed with a reference instrument (SYSMEX SF-3000) at the levels 65, 85, 141, 151 and 179 g/1 considering the haemoglobin values.
  • SYSMEX SF-3000 a reference instrument
  • An alternative way would be to provide a reference blood sample exhibiting a known haemoglobin concentration and then dilute said reference blood sample to obtain a set of reference samples having different known haemoglobin concentrations.
  • Still another way would be to provide a plurality of reference blood samples exhibiting unknown haemoglobin concentrations and then determine the haemoglobin concentrations in said reference blood samples to obtain a set of reference samples having different known haemoglobin concentrations.
  • the corresponding imaginary part of the complex impedance for each sample was determined at 400 kHz using the above-mentioned network analyser (Rohde & Schwarz ZVC).
  • the impedance results obtained at 400 kHz were correlated with the haemoglobin results obtained with the reference instrument.
  • the equation of a calibration curve within the mentioned range (65 - 179 g/1) was determined (see Fig. 2).
  • the standard curve shows the haemoglobin values (Hb) of the above-mentioned blood samples, as obtained with the reference instrument, as a function of their corresponding imaginary parts of the complex impedance.
  • Hb haemoglobin values
  • the factor A and the coefficient B were found to be 32,62 and -1632, respectively.
  • the R and the R-square values were 0.9955 and 0,9910, respectively (see Fig. 2).
  • the calculated haemoglobin values (X- values), ranging between 80-180 were correlated with the haemoglobin values from the reference instrument (Y- values).
  • the R and the R-square values were 0.8563 and 0,7333, respectively (see Fig. 3).
  • the standard curve for the measurement performed at 500 kHz was constructed in the same manner as in Example 1 , which for this frequency resulted in A and B being 31,60 and -1451, respectively, and R and R-square being 0,9966 and 0,9932, respectively (see Fig. 4).
  • the standard curve for the measurement performed at 600 kHz was constructed in the same manner as in Example 1 , which for this frequency resulted in A and B being 30,67 and -1336, respectively, and R and R-square being 0,9974 and 0,9949, respectively (see Fig. 6).
  • the standard curve for the measurement performed at 700 kHz was constructed in the same manner as in Example 1, which for this frequency resulted in A and B being 29,88 and -1255, respectively, and R and R-square being 0,9981 and 0,9961, respectively (see Fig. 8) .
  • the standard curve for the measurement performed at 800 kHz was constructed in the same manner as in Example 1, which for this frequency resulted in A and B being 29,42 and -1200, respectively, and R and R-square being 0,9984 and 0,9968, respectively (see Fig. 10).
  • the standard curve for the measurement performed at 900 kHz was constructed in the same manner as in Example 1 , which for this frequency resulted in A and B being 29,13 and -1155, respectively, and R and R-square being 0,9986 and 0,9971, respectively (see Fig. 12).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Ecology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention concerne un procédé d'analyse de sang qui consiste à détecter la partie imaginaire de l'impédance complexe dans un prélèvement sanguin dont la concentration d'hémoglobine est inconnue et à établir une corrélation directe de la partie imaginaire de l'impédance complexe avec la concentration d'hémoglobine contenue dans ce prélèvement sanguin.
PCT/SE2002/001530 2001-08-29 2002-08-27 Systeme et procede d'analyse de sang Ceased WO2003019166A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0102896A SE521208C2 (sv) 2001-08-29 2001-08-29 System och förfarande för blodanalys
SE0102896-8 2001-08-29

Publications (1)

Publication Number Publication Date
WO2003019166A1 true WO2003019166A1 (fr) 2003-03-06

Family

ID=20285187

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE2002/001530 Ceased WO2003019166A1 (fr) 2001-08-29 2002-08-27 Systeme et procede d'analyse de sang

Country Status (2)

Country Link
SE (1) SE521208C2 (fr)
WO (1) WO2003019166A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7488601B2 (en) * 2003-06-20 2009-02-10 Roche Diagnostic Operations, Inc. System and method for determining an abused sensor during analyte measurement
US7597793B2 (en) 2003-06-20 2009-10-06 Roche Operations Ltd. System and method for analyte measurement employing maximum dosing time delay
US7981363B2 (en) 1997-12-22 2011-07-19 Roche Diagnostics Operations, Inc. System and method for analyte measurement
AU2009248430B2 (en) * 2002-02-10 2011-10-13 Agamatrix, Inc. Method and apparatus for assay of electrochemical properties

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0417796A2 (fr) * 1989-09-13 1991-03-20 Kabushiki Kaisha Toyota Chuo Kenkyusho Appareil de mesure d'hématocrite

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0417796A2 (fr) * 1989-09-13 1991-03-20 Kabushiki Kaisha Toyota Chuo Kenkyusho Appareil de mesure d'hématocrite

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JAFFRIN M.Y. ET AL.: "Comparison of optical, electrical and centrifugation techniques for haematocrit monitoring ofg dialysed patients", MED. BIOL. ENG. COMPUT., vol. 37, 1999, pages 433 - 439, XP000835037 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7981363B2 (en) 1997-12-22 2011-07-19 Roche Diagnostics Operations, Inc. System and method for analyte measurement
US8691152B2 (en) 1997-12-22 2014-04-08 Roche Operations Ltd. System and method for analyte measurement
AU2009248430B2 (en) * 2002-02-10 2011-10-13 Agamatrix, Inc. Method and apparatus for assay of electrochemical properties
US7488601B2 (en) * 2003-06-20 2009-02-10 Roche Diagnostic Operations, Inc. System and method for determining an abused sensor during analyte measurement
US7597793B2 (en) 2003-06-20 2009-10-06 Roche Operations Ltd. System and method for analyte measurement employing maximum dosing time delay
US8377707B2 (en) 2003-06-20 2013-02-19 Roche Diagnostics Operations, Inc. System and method for determining an abused sensor during analyte measurement

Also Published As

Publication number Publication date
SE0102896L (sv) 2003-03-01
SE0102896D0 (sv) 2001-08-29
SE521208C2 (sv) 2003-10-14

Similar Documents

Publication Publication Date Title
EP1456666B1 (fr) Methode pour la determination du glucose
US10809246B2 (en) Hemolysis detection method and system
KR100786983B1 (ko) 샘플 유형 및 양 검출을 이용한 바이오센서 장치 및 방법
US7829339B2 (en) Method for casein determination in milk
KR20100005209A (ko) 비선형 샘플 응답을 이용한 분석물 측정을 위한 시스템 및 방법
AU2003234944A1 (en) Methods of Determining Glucose Concentration in Whole Blood Samples
EP2873969A1 (fr) Système de mesure d'hématocrite et procédé de mesure l'utilisant
CN112034009A (zh) 一种钠离子校正的红细胞压积测试系统及测试方法
WO2003019166A1 (fr) Systeme et procede d'analyse de sang
US5633169A (en) Measurement of carbon dioxide in blood
CA2514743C (fr) Amelioration de la qualite d'une analyse hematologique
US6212418B1 (en) Methods, kits, electrodes and compositions for assessing the level of an analyte of interest in fluid samples
CA1307825C (fr) Methode et appareil pour l'analyse du sang par dosage unique
JPS59168371A (ja) 血液生化学成分の分析方法およびその装置
AU1384997A (en) Method for testing a cell suspension

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ CZ DE DE DK DK DM DZ EC EE EE ES FI FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GM HR HU ID IL IN IS JP KE KG KP KZ LC LK LR LS LT LU LV MA MD MK MN MW MX MZ NO NZ OM PH PT RO RU SD SE SG SI SK SL TJ TM TN TR TZ UA UG US UZ VC VN YU ZA ZM

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ UG ZM ZW AM AZ BY KG KZ RU TJ TM AT BE BG CH CY CZ DK EE ES FI FR GB GR IE IT LU MC PT SE SK TR BF BJ CF CG CI GA GN GQ GW ML MR NE SN TD TG

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 69(1) EPC (FORM 1205A, 29-06-04)

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP