WO2009071102A1 - Procédé et dispositif optique pour mesurer des concentrations de substances dans des fluides biologiques - Google Patents

Procédé et dispositif optique pour mesurer des concentrations de substances dans des fluides biologiques Download PDF

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Publication number
WO2009071102A1
WO2009071102A1 PCT/EE2008/000026 EE2008000026W WO2009071102A1 WO 2009071102 A1 WO2009071102 A1 WO 2009071102A1 EE 2008000026 W EE2008000026 W EE 2008000026W WO 2009071102 A1 WO2009071102 A1 WO 2009071102A1
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WO
WIPO (PCT)
Prior art keywords
concentration
sample
cuvette
biological fluid
substance
Prior art date
Application number
PCT/EE2008/000026
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English (en)
Inventor
Ivo Fridolin
Jana Jerotskaja
Kai Lauri
Merike Luman
Original Assignee
Tallinn University Of Technology
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 Tallinn University Of Technology filed Critical Tallinn University Of Technology
Priority to EEP201000054A priority Critical patent/EE05622B1/xx
Publication of WO2009071102A1 publication Critical patent/WO2009071102A1/fr

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/33Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light

Definitions

  • This invention relates to a novel method and a device for measuring concentration of substances, preferable uric acid, in biological fluids. More specifically, the present invention relates to an optical method utilizing spectrum of the biological fluid and the Savitzky-Golay algorithm to determine the concentration of the substances on-line.
  • Uric acid a final product of the metabolism of purine, is very important biological molecule present in body fluids. It is mostly excreted from human body through the kidneys in the form of urine. The concentration of uric acid in blood increases when the source of uric acid increases or the kidney malfunctions. Hyperuricemia is a symptom when the uric acid concentration is above 7 mg/dL. Uric acid is hard to dissolve in blood and will crystallize when supersaturated. The uric acid crystallites deposit on the surface of skin, in joints, and especially in toes and results in gout. The analysis of the uric acid concentration in blood helps to diagnose gout.
  • hyperuricemia In addition to gout, hyperuricemia is connected with lymph disturbance, chronic hemolytic anemia, an increase of nucleic acid metabolism and kidney malfunction. High caloric foods and alcohol as well as disturbances of organs and tissues are the main causes of hyperuricemia and even gout. Harm can be prevented and reduced by an early diagnosis and monitoring. A simple and inexpensive detecting system helps patients to detect the uric acid concentration on their own.
  • Uric acid can be determined in several different ways. Two of the most common methods are (1) reduction method by the reaction of uric acid with alkaline phosphotungstate, and (2) the enzymatic method by the enzyme urease.
  • reduction method by the reaction of uric acid with alkaline phosphotungstate
  • enzymatic method by the enzyme urease.
  • uric acid is estimated by reducing alkaline phosphotungstate to tungsten blue and measuring the colored product in a colorimeter.
  • the demerits of this method include: 1) some compounds similar to uric acid and ascorbic acid contained in the sample of biological fluid affect the test accuracy; 2) the operation is complex, needs lots of agents which are hard to keep, and should be operated by professionals; 3) the sample must be de- protein pretreated; and 4) the necessary equipment is expensive.
  • the second method detects uric acid by optical colorimetry and electrochemistry and is classified into uricase-ultraviolet absorption, uricase-peroxidase, uricase-catalase and uricase- electrode methods, wherein the former three methods make ⁇ se of the color of reaction products and quantitatively detect uric acid of by colorimetry.
  • the decrease in absorbance is proportional to the amount of uric acid initially present.
  • the automatic bio-analyzers used in central bio-laboratories of hospitals detect uric acid by optical colorimetry.
  • An improving system for quantification of biochemical components in biological fluids during analysis where a component reacts with an analyte is described in US6121050.
  • the blood sample should be pretreated to be serum or plasma first.
  • the merits of the automatic bio-analyzers reside in mass detecting, automation and quickness.
  • an automatic bio-analyzer cannot be applied in household detecting because it requires professionals to operate, is expensive, and is particularly hard to store the detecting agents.
  • the uricase-electrode method detects uric acid by electrochemistry.
  • the electrodes can be divided as enzymatic and non-enzymatic.
  • the former produced by a complex production process is hard to store and thus is only suitable for research.
  • the merits of the described method are that it does not need blood samples, no disposables or chemicals, and is fast.
  • the described method is general and does not specify methodology to measure exclusively a single compound and is meant to apply only for dialysis monitoring. Moreover, no results about the concentration measurements are presented. More exact description about the uric acid and urea measurements using the abovementioned method is given in a scientific papers (Uhlin, Lindberg et al. 2005), (Uhlin, Fridolin et al. 2005).
  • Another method relates to a method for dialysis monitoring method and apparatus using near infrared radiation, described in WO9819592.
  • the merits of the described method are similar to that of the UV -radiation.
  • the described method does not measure uric acid and utilizes near infrared radiation spectrometry with different technical and optical considerations.
  • near infrared radiation spectrometry the principial component analysis using calibration and prediction stage is described in US5886347.
  • the objective of the invention is, therefore, a new method and a device for measuring concentration of substances, such as uric acid, in biological fluids. More specifically, the present invention relates to an optical method utilizing optical spectrum of the biological fluid and the Savitzky-Golay (or Savitsky-Golay) algorithm, and concentration calculation algorithm containing the transforming function to determine on-line the concentration of the substances, which can be effected directly at the bed-side and which avoids the disadvantages caused by the analysis in a laboratory.
  • Savitzky-Golay or Savitsky-Golay
  • Another object of the present invention is to provide a novel and practical optical uric acid detecting method and device which detects concentration of uric acid in the biological fluids and can be represented directly and easily on the monitor or screen printed.
  • the novel method and device does not require any chemical disposables, neither expensive uricase nor both L-ascorbic acid oxidase, and can be easily made and mass-produced providing an environment-friendly optical method.
  • a still further object of the present invention is to provide a method for assessing routine clinical monitoring in order to face risks of higher mortality in patients (e.g. in dialysis).
  • a still further object of the present invention is to provide a novel, rapid, convenient and safe method for detecting concentration of substances in a liquid sample.
  • the liquid sample can be directly dropped on the detecting cuvette for in-vitro measurements or sent a flowing stream of fluid through a flow-cuvette for on-line monitoring.
  • the method is suitable for household use when being applied to detect the concentration of substances in the biological fluids.
  • Fig. 1 depicts a block diagram of one embodiment of the invention.
  • Fig. 2 depicts a block diagram of another embodiment of the invention applied for uric acid concentration measurements during dialysis.
  • Fig. 3 shows the linear relationship between uric acid (UA) concentration measured by a known method and at the laboratory.
  • Fig. 4 shows the linear relationship between uric acid (UA) concentration measured by the invented (new) method and at the laboratory.
  • the device for measuring concentration of certain substances (e.g., uric acid) 5 in a biological fluid 1 comprises: an optical module 2, comprising a spectrophotometrical system, comprising a light source and a light detector; a measuring cuvette for holding a sample of the biological fluid so that the light can be led through the sample; a signal processing module 3 comprising a data acquisition module and a spectra processing module, and a data representing module 4.
  • the light source can be either a broadband light source or a narrowband light source. If broadband light source is used, either a broadband detector and a filter can be used, or narrowband detectors.
  • the optical module is operating in the ultra violet region (wavelength range 190-330 nm).
  • FIG. 2 Another embodiment of the invention is shown in Fig. 2.
  • the device is applied for determining the concentration of substances such as uric acid during dialysis in spent dialysate 6.
  • the device comprises spectrophotometer 7, a signal processing unit 8 for smoothing and derivate calculation, a unit 9 for calculating concentration 10 of the substance in the spent dialysate.
  • the measuring cuvette can be, e.g., adapted for in- vitro measurements, or designed for the on-line measurements.
  • the spectra processing module is adapted to execute the Savitzky-Golay algorithm for smoothing and calculating the derivate of the measured spectra.
  • the spectra processing module may be further adapted to execute a concentration calculation algorithm comprising a transforming function calculating the concentration of certain substance in the biological fluid.
  • the data representing module is adapted to execute a program for data representation and comprises or is connected to a data visualization module, e.g., a monitor, a display, or a printing device.
  • a data visualization module e.g., a monitor, a display, or a printing device.
  • the optical module consisted of a double-beam spectrophotometer (SHIMATSU UV-2401 PC, Japan) with an accuracy of ⁇ 1% on the dialysate samples taken at pre-determined times during dialysis. Spectrophotometric analysis over a wavelength range of 190-380 nm was performed by a cuvette with an optical path length of 1 cm.
  • the data acquisition module consisted of a PC incorporated in the spectrophotometer using UV-PC software (UV-PC personal spectrophotometer software, version 3.9 for Windows).
  • the obtained UV-absorbance values were processed and presented by a signal processing module using Savitzky-Golay smoothing algorithm, and the derivative calculating algorithm and EXCEL (Microsoft Office Excel 2003) software (concentration calculation algorithm containing the transforming function calculating the concentration of certain substance in the biological fluid).
  • the data representing module was either the computer screen or a printer.
  • Table 1 Summary results for the different methods to measure concentration of the uric acid.

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  • Physics & Mathematics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

Le procédé et le dispositif de l'invention permettent de mesurer la concentration de substances, de préférence, d'acide urique, dans des fluides biologiques. Les mesures sont de type optique et utilisent le spectre du fluide biologique, l'algorithme de Savitzky-Golay, et un algorithme de calcul de la concentration contenant la fonction de transformation pour déterminer la concentration des substances dans des spécimens in vitro ou des fluides en écoulement en continu. Le procédé et le dispositif déterminent la concentration des substances in vitro ou en continu au moyen d'une cuvette de mesure utilisable pour des mesures spécifiées.
PCT/EE2008/000026 2007-12-04 2008-12-04 Procédé et dispositif optique pour mesurer des concentrations de substances dans des fluides biologiques WO2009071102A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EEP201000054A EE05622B1 (et) 2007-12-04 2008-12-04 Seade ja meetod bioloogilises vedelikus sisalduvate ainete kontsentratsiooni m??tmiseks

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US99215607P 2007-12-04 2007-12-04
US60/992,156 2007-12-04

Publications (1)

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WO2009071102A1 true WO2009071102A1 (fr) 2009-06-11

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011147425A1 (fr) 2010-05-27 2011-12-01 Tallinn University Of Technology Procédé et dispositif de mesure et de surveillance des concentrations de substances dans un liquide biologique
WO2012000521A1 (fr) 2010-06-28 2012-01-05 Tallinn University Of Technology Procédé et dispositif pour déterminer la teneur en toxines urémiques liées aux protéines et moyennes dans un fluide biologique
DE202010017537U1 (de) 2010-12-16 2012-02-09 Ldiamon As Nachweisvorrichtung zur Bestimmung des Urea-Gehalts
WO2012152514A1 (fr) 2011-05-11 2012-11-15 Ldiamon As Procédé et dispositif de dosage pour déterminer le taux d'acide urique et de créatinine
EP2942614A1 (fr) 2014-05-08 2015-11-11 B. Braun Avitum AG Dispositif et procédé de commande de dispositif destiné à la détermination de concentration quantitative de substances sélectionnées dans un liquide extraites par filtration d'un corps d'un patient
CN110411969A (zh) * 2019-08-02 2019-11-05 淮阴师范学院 紫外分光光度法测定禽类粪便中尿酸含量的方法

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US6674526B1 (en) * 2000-08-03 2004-01-06 Ralf Marbach Methods and apparatus for improving the long-term stability of spectroscopic quantitative analyses
GB2390420A (en) * 2002-07-02 2004-01-07 James Samsoondar Method for calibrating spectrophotometric apparatus
US20050119541A1 (en) * 1999-10-08 2005-06-02 Lorenz Alexander D. Method of adapting in-vitro models to aid in noninvasive glucose determination

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US5351686A (en) * 1990-10-06 1994-10-04 In-Line Diagnostics Corporation Disposable extracorporeal conduit for blood constituent monitoring
US20050119541A1 (en) * 1999-10-08 2005-06-02 Lorenz Alexander D. Method of adapting in-vitro models to aid in noninvasive glucose determination
US6674526B1 (en) * 2000-08-03 2004-01-06 Ralf Marbach Methods and apparatus for improving the long-term stability of spectroscopic quantitative analyses
GB2390420A (en) * 2002-07-02 2004-01-07 James Samsoondar Method for calibrating spectrophotometric apparatus

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Title
FRIDOLIN I ET AL: "ON-LINE MONITORING OF SOLUTES IN DIALYSATE USING ABSORPTION OF ULTRAVIOLET RADIATION: TECHNIQUE DESCRIPTION", INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS, MILAN, IT, vol. 25, no. 8, 1 August 2002 (2002-08-01), pages 748 - 761, XP008101248, ISSN: 0391-3988 *
J.T. OLESBERG ET AL.: "Online Measurement of Urea Concentration in Spent Dialysate during Hemodialysis", CLINICAL CHEMISTRY, vol. 50, no. 1, 2004, pages 175 - 181, XP002520388 *
SAVITZKY A ET AL: "SMOOTHING AND DIFFERENTIATION OF DATA BY SIMPLIFIED LEAST SQUARES PROCEDURES", ANALYTICAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. COLUMBUS, US, vol. 36, no. 8, 1 July 1964 (1964-07-01), pages 1627 - 1639, XP000560623, ISSN: 0003-2700 *
UHLIN F ET AL: "ESTIMATING TOTAL UREA REMOVAL AND PROTEIN CATABOLIC RATE BY MONITORING UV ABSORBANCE IN SPENT DIALYSATE", NEPHROLOGY DIALYSIS TRANSPLANTATION, OXFORD UNIVERSITY PRESS, GB, vol. 20, 1 January 2005 (2005-01-01), pages 2458 - 2464, XP001167226, ISSN: 0931-0509, [retrieved on 20050802] *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011147425A1 (fr) 2010-05-27 2011-12-01 Tallinn University Of Technology Procédé et dispositif de mesure et de surveillance des concentrations de substances dans un liquide biologique
WO2012000521A1 (fr) 2010-06-28 2012-01-05 Tallinn University Of Technology Procédé et dispositif pour déterminer la teneur en toxines urémiques liées aux protéines et moyennes dans un fluide biologique
DE202010017537U1 (de) 2010-12-16 2012-02-09 Ldiamon As Nachweisvorrichtung zur Bestimmung des Urea-Gehalts
WO2012152514A1 (fr) 2011-05-11 2012-11-15 Ldiamon As Procédé et dispositif de dosage pour déterminer le taux d'acide urique et de créatinine
DE102011101193A1 (de) 2011-05-11 2012-11-15 Ldiamon As Verfahren und Nachweisvorrichtung zur Bestimmung des Harnsäure- und Kreatinin-Gehalts
EP2942614A1 (fr) 2014-05-08 2015-11-11 B. Braun Avitum AG Dispositif et procédé de commande de dispositif destiné à la détermination de concentration quantitative de substances sélectionnées dans un liquide extraites par filtration d'un corps d'un patient
DE102014106489A1 (de) 2014-05-08 2015-11-12 B. Braun Avitum Ag Vorrichtung und Vorrichtungs-Steuerungsverfahren zur quantitativen Konzentrationsbestimmung ausgewählter aus einem Patientenkörper ausgefilterter Substanzen in einer Flüssigkeit
US9423338B2 (en) 2014-05-08 2016-08-23 B. Braun Avitum Ag Apparatus and apparatus control method for the quantitative concentration determination of selected substances filtered out of a patient's body in a fluid
CN110411969A (zh) * 2019-08-02 2019-11-05 淮阴师范学院 紫外分光光度法测定禽类粪便中尿酸含量的方法
CN110411969B (zh) * 2019-08-02 2021-10-01 淮阴师范学院 紫外分光光度法测定禽类粪便中尿酸含量的方法

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EE05622B1 (et) 2013-02-15
EE201000054A (et) 2010-08-16

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