WO1990007109A1 - A method of photometric in vitro determination of the content of an analyte in a sample of whole blood - Google Patents

A method of photometric in vitro determination of the content of an analyte in a sample of whole blood Download PDF

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Publication number
WO1990007109A1
WO1990007109A1 PCT/DK1989/000301 DK8900301W WO9007109A1 WO 1990007109 A1 WO1990007109 A1 WO 1990007109A1 DK 8900301 W DK8900301 W DK 8900301W WO 9007109 A1 WO9007109 A1 WO 9007109A1
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WO
WIPO (PCT)
Prior art keywords
sample
radiation
measuring chamber
sampling device
transparent
Prior art date
Application number
PCT/DK1989/000301
Other languages
French (fr)
Inventor
Finn Chresten Lundsgaard
Willy Andersen
Niels-Henrik Jensen
Original Assignee
Radiometer A/S
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.)
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Publication date
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Application filed by Radiometer A/S filed Critical Radiometer A/S
Priority to DE68918292T priority Critical patent/DE68918292T2/en
Priority to JP2501614A priority patent/JPH0833390B2/en
Priority to EP90900767A priority patent/EP0534945B1/en
Publication of WO1990007109A1 publication Critical patent/WO1990007109A1/en
Priority to DK911092A priority patent/DK109291D0/en

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    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
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    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251—Colorimeters; Construction thereof
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    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
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    • G01N21/255—Details, e.g. use of specially adapted sources, lighting or optical systems
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    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
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    • G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
    • G01N21/274—Calibration, base line adjustment, drift correction
    • G01N21/276—Calibration, base line adjustment, drift correction with alternation of sample and standard in optical path
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    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G01N2021/3148—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths using three or more wavelengths
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    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G01N2021/3166—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths using separate detectors and filters
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    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
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    • G01N21/64—Fluorescence; Phosphorescence
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    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
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    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
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    • G01N2035/00316—Detecting door closure
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    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1062—General features of the devices using the transfer device for another function for testing the liquid while it is in the transfer device
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    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
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    • G01N21/80—Indicating pH value
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    • G01N2201/1288—Calibration medium periodically inserted in one cell

Definitions

  • the present invention relates to a method of photometric in vitro determination of the content of an analyte in a sample of whole blood as set forth in the introductory part of claim 1.
  • a number of clinical chemistry analyzers exists which analyzers consist of a combination of disposable components, which are only used for one single analysis operation and only get in touch with one single sample, and an analysing section adapted for receiving the sample containing disposable device and containing the additional components necessary for accomplishing a clinical chemical analysis.
  • the sampling device and the disposable device constitute one and the same device.
  • International patent application WO 86/00138 discloses a device with a cavity sufficiently small for a given sample to be sucked into the cavity by capillary effect.
  • the cavity is provided with an electrode structure and possibly a coating of a material adapted to the analysis to be performed with the equipment.
  • the electrode structure provided in the cavity may i.a. be a potentiometric ion sensitive electrode structure or an amperometric electrode structure. The latter is described in connection with determination of hydrogen peroxide and oxygen in the sample.
  • British patent application GB 2025065 (Meiattini, F. et. al.) is known a plunger syringe for withdrawal of a blood sample.
  • the blood sample is analysed by means of sensors incorporated in the syringe plunger. It is thereby avoided to transfer the sample to a sample station.
  • the sensors are adapted for connection with an analyzer via conductors for registrating, processing, and outprinting analysis data.
  • the specific sensors described in the specification of the said British patent application GB 2025065 are electrochemical sensors for blood gases and blood electrolytes.
  • the object of the invention is to provide a method by which the above-mentioned problems connected with photometric analysis of a whole blood sample located in the sample container of a sampling device during the analysis procedure, are readily eliminated. This is achieved by the method according to the invention which method is characterized by the characteristic features of claim 1.
  • “In vivo locality” denotes in the present context a lo- cality being in direct connection with the blood circulation or being a locality in the blood circulation itself.
  • Sampling by arterial puncture, whereby the blood sample is transferred from the artery to the sample container by a thin needle, as well as via an arterial catheter or via capillary puncture are sampling methodologies, in which the blood sample is transferred directly from an in vivo locality to a sample container.
  • the radiation emitted from the radiation source may be broad banded as well as monochromatic radiation and may belong to the ultraviolet range, the visible range, the near infrared range and/or the infrared range.
  • the radiation source may comprise one component or several components emitting radiation at their respective particular wavelength range.
  • the radiation detector as well may comprise one component detecting radiation at a particular wavelength range or several components detecting radiation at their respective particular wavelength ranges.
  • the several components of the radiation source may be provided as one integrated device or as separate devices. The same applies to the radiation detector.
  • the controlled deformation of the sample chamber is a deformation reducing the volume of the measuring chamber to such extent that the measuring chamber is either completely or locally drained for blood sample.
  • local draining is understood that the part of the measuring chamber traversed by the radiation is drained for blood sample.
  • the optical communication is established by placing the sample container in a sample container station of an analyzer.
  • the optical communication may be established by one or several cables which via means for contacting the sample container and optical fibres establish optical communication between the optical system and the sample container.
  • the transparent body used in the method according to the present invention is made of a material with a homegeneous structure, in particular a homogeneous surface making the material suited" for use in photometric transmission analysis.
  • the body is shaped as a disc or plate with two planoparallel surfaces and a thickness of less than 1 mm, preferably 1-500 urn, in particular 5-250 um and most preferably 8-200 um.
  • the indicator may be fixed by any suitable immobilization method such as by absorption, adsorption, ion binding or covalent binding.
  • Such determination of several analytes within one measuring chamber may be accomplished by using a transparent body to which several indicators are fixed.
  • a transparent body containing a reagent which on reaction with the analyte forms a reaction product changing the transmission properties of the body in relation to the analyte concentration in the environment of the body would be suitable for the determination of certain analytes.
  • it may be the reaction product per se which changes the transmission properties of the body or an indicator which is fixed to the body and is affected by the reaction product.
  • the method according to the invention aims at such analytes as blood gases, cationic and anionic components in blood (blood electrolytes), metabolites, hormones, enzymes, proteins, drugs and other chemical species which is or may be found in blood.
  • examples of such analytes are oxygen, carbon dioxide, H + (or pH),
  • a body made of silicone rubber or another transparent, homogeneous material with a high dissolution power for CO 2 is preferred.
  • the CO 2 determination is accomplished on the basis of testing the transmission properties of the body for 4.2 um radiation.
  • the basic principles for such determination are disclosed in the specification of British patent application GB 2160646 and in the specification of European patent application EP 253559.
  • a body made of a polymer material with -OH groups available for immobilization, e.g. a cellulose or cellophane material, and with a pH indicator which may be covalently bound thereto, e.g. an indicator comprising the reactive group -SO 2 -CH 2 -CH 2 -O-SO 3 H.
  • a pH indicator which may be covalently bound thereto, e.g. an indicator comprising the reactive group -SO 2 -CH 2 -CH 2 -O-SO 3 H.
  • Cellophane in particular has physical properties suitable for the present purpose, such as a well-defined thickness and a homogeneous structure.
  • the invention also relates to a sampling device comprising a sample container with a measuring chamber having at least locally transparent opposite wall parts and having the characteristic features set forth in the characterizing part of claim 11.
  • the locally transparent wall parts comprise planoparallel parts extending parallel with the planoparallel surfaces of the transparent body.
  • the transparent body may be loosely accomodated in the measuring chamber or it may be fixed to a wall part.
  • the sample container may comprise one measuring chamber or several measuring chambers disposed in series or in parallel.
  • the sample container is made of an injection mouldable polymeric base material, e.g. the material sold under the trade name ARNITETM from AKZO, Arnheim, Holland.
  • the wall parts of the measuring chamber are preferably made of a polymer material having a low carbon dioxide permeability and suitable transmission properties for radiation at the wavelengths relevant to the abovementioned determinations, said wavelengths being discussed at another page.
  • a suitable material is an ethylene vinylalcohol copolymer of the type EVAL-E TTM sold by
  • the use of a sample container with a dimension sufficiently small for the sample container to be filled by capillary effect is preferred.
  • a sample container with an inlet located in a coupling means, preferably a Luer cone, for coupling the sample container to a needle or a catheter is preferred.
  • a coupling means preferably a Luer cone
  • the invention further comprises an analyzer for use in the method according to the invention, said analyzer having the characteristic features set forth in the characterizing part of claim 21.
  • the analyzer comprises data processing means for processing the registered radiation data for deriving the content of the actual analyte in the actual sample from these.
  • the analyzer is adapted for connection to a separate data processing unit.
  • the analyzer comprises means for displaying the analyte content.
  • the analyzer is adapted for connection with means such as, e.g. a data screen, a display, a printer, or a plotter.
  • Fig. 1 is a perspective view of a preferred embodiment of an analyzer and a sample container, which together constitute the system according to the invention for photometric in vitro determination of an analyte in a blood sampler
  • FIG. 2 is an enlarged schematic view from above of the sample container station of the analyzer with the sampling device;
  • Fig. 3, Fig. 4 and Fig. 5 are views of a preferred embodiment of a sampling device according to the invention;
  • Fig. 6 is an electric block diagram of the analyzer shown in Fig, 1;
  • Fig. 7 shows the photometric basis for determination of pH
  • Fig. 8 is a perspective view of a sample container for use in determining pH
  • Fig. 9 is a partial cross section of an optical unit in a system comprising an analyzer according to the invention and a sampling device according to the invention for photometric determination of pH and with a schematic representation of the components forming parts of the optical unit;
  • like reference numerals designate like parts.
  • the analysis system shown in Fig. 1 and generally designated 10 is a compact portable "stand-alone" system, which is suited for decentral use, i.e. use outside a regular laboratory environment, e.g. in an operating room or at an intensive ward.
  • the analysis system 10 comprises a blood sampling device 2 for disposable use and used in connection with an analyzer 11.
  • the sampling device 2 is more explicitly described in connection with the description of Fig. 3-5 below.
  • the sample container 2 and the analyzer 11 are adapted to interact in the way that the analyzer 11 has a sample container station 1 with an optical section 3 adapted for receiving the sampling device 2 or possibly the sample container of the sampling device, so that the optical communication between the sampling device 2 and the optical components of the optical unit 3, which is necessary for photometric analysis, is obtained.
  • the sample container station 1 can be closed by a cover
  • Closing the cover 8 further results in a signal being sent to the controlling unit of the analyzer and indieating the start of an analysis procedure.
  • An operator can control the operation of the analyzer by means of a keyboard 5 and a display 6.
  • the analyzer 11 preferably also comprises a printer, which can produce an outprint 7 of i.a. the analysis results obtained by the analyzer.
  • the optical components comprising of radiation sources and radiation detectors are activated, whereupon the ana- lyzer 11 calculates one or several parameters on the basis of the signals from the radiation detectors.
  • the result of the calculations is displayed on the display 6 and is printed on the paper outprint 7 by the printer.
  • the cover 8 is opened and the sampling device 2 is displaced from the sample container station 1 and disposed of.
  • FIG. 2 shows a partially schematic section of the sample container station 1 viewed from above.
  • the optical section 3 comprises four optical units 30, 40, 50, and 60 adapted for determination of pH (unit 30), carbon dioxide (unit 40), oxygen (unit 50) and hemoglobin and oxygen saturation (unit 60) respectively.
  • the sample container of the sampling device with four measuring chambers is placed in a slot 4 in the optical section 3.
  • the analyzer 11 is shown containing four optical units it can in principle contain an arbitrary number and/or an arbitrary combination of units beyond the unit utilized in the method according to the invention.
  • Fig. 3 shows a longitudinal section of the sampling device 2 and four segments of this in a larger scale.
  • the sampling device comprises a body 23, which at least in specified areas is made of a material transparent for the relevant radiation.
  • the body 23 has a continuous conduit 22 locally extended for forming measuring chambers 300, 400, 500, and 600.
  • the section of the body 23 surrounding the inlet aperture is provided with a Luer cone and is therefore suitable for being mounted with a needle 20 of the type normally used for blood sampling.
  • the section 25 of the body 23 pointing away from the inlet aperture is adapted for coupling with a traditional plunger syringe.
  • a plunger syringe is used as aid at the sampling in certain situations, e.g. when the patient, whose blood gas parameters are to be determined, has a very low blood pressure.
  • the measuring chambers 300, 400, 500, and 600 communicate optically with the optical units 30, 40, 50, and 60.
  • the measuring chamber 300 optically communicating with the optical unit 30 is adapted for determination of pH in the blood sample and contains a cellophane membrane 316, to which is immobilized a pH absorbance indicator.
  • the indicator is in chemical equilibrium with the blood sample, the ratio between the acid form of the indicator and the basic form of the indicator reflects the pH value of the blood sample.
  • the chemical and photometric basis for the pH determination appears from Fig. 7, 8, and 9 and of the description of these.
  • An embodiment of the optical unit 30 appears from fig. 9 and the description of this.
  • the sampling device 2 has an integral needle protecting means 26.
  • the needle protecting means 26 is a tubular jacket movable in the axial direction of the sample container between a first position, wherein the jacket exposes the point of the needle, and a second position, wherein the jacket surrounds the point of the needle.
  • Fig. 3 shows the protecting jacket 26 in the first position, in which it is placed at the sampling moment.
  • Fig. 4 shows a longitudinal section of the sampling device. The section is placed perpendicular to the section shown in Fig. 3.
  • the sample container body 23 consists of two halves, of which only one is seen in Fig. 4.
  • Fig. 5 shows finally the same section as Fig. 3 but in Fig. 5 the protecting jacket is displaced to the second position, wherein it surrounds the point of the needle.
  • the jacket 26 is displaced to this second position immediately after the sampling.
  • Fig. 6 shows the electrical block diagram for the analyzer 11 and speaks for itself.
  • Fig. 7 shows the absorption spectrum for a pH absorption indicator N-9 more closely described below in connection with Fig. 8.
  • the indicator is immobilized to a cellophane membrane by the method also described in detail in connection with Fig. 8.
  • the spectrum is recorded by a spectrophotometer of the type Shimadzu Spectrophotometer UV 250.
  • the absorption measurements were performed on a cellophane membrane (6 ⁇ 12 ⁇ 0.028 mm) with immobilized indicator.
  • the cellophane was placed in the cuvette of the spectrophotometer in a holder adapted thereto and with dimensions adapted to the dimensions of the cuvette.
  • each buffer consisted of 500 ml 0.1 M KH 2 PO 4 to which was added the necessary amount of 0.1 M NaOH.
  • the pH value of each buffer was potentiometrically measured (Radiometer PHM80) by means of a glass electrode (Radiometer GK2402C).
  • Fig. 8 shows an embodiment of a sample container for use in determination of pH in a blood sample.
  • the sample container generally designated 3000, is intended to interact with an analyzer with an optical unit as the one more closely described below in connection with Fig. 9.
  • the sample container consists of two halves 3001 and 3002.
  • halves are made from a transparent plastic materi al, e.g. softened polymethyl methacrylate of the type DE- GALANTM SZ70 (Superfos, Copenhagen, Denmark).
  • the two halves are assembled by pins 3005 and 3006 in the half 3001 engaging corresponding, not shown recesses in the half 3002, while not shown pins in this engage recesses 3007 and 3008 in the half 3001.
  • the two halves are hereafter welded together by ultrasonic welding.
  • the line 3009 of material outlined on the lower half 3001 shown in the figure forms a welding seam after the welding. This line of material lies along the edge of a longitudinal conduit 3004, which centrally expands transversely and forms a measuring chamber 3011.
  • a wall section 3010 of the upper half 3002 shown in the figure is elastically deformable and for that reason has a very reduced wall thickness compared to the rest of the half.
  • a cellophane membrane 3003, to which there is immobilized a pH indicator, is placed in the measuring chamber 3011.
  • the pH indicator is delivered by Merck, Darmstadt, West Germany under the name N-9 and is known to contain the reactive group
  • the immobilisation of the indicator to the membrane takes place in a process, whereby the above mentioned reactive group is transformed with sodium hydroxide into a vinyl sulphone group, which can be coupled to cellophane previously activated by conditioning the cellophane in 0.1 M NaOH for 15 minutes.
  • the reaction scheme describing the coupling reaction between the indicator and the cellophane membrane is:
  • R here designates an aryl group.
  • the quantitative immobilisation procedure is the following :
  • Struers, Copenhagen, Denmark is after the above mentioned conditioning with NaOH prepared with an indicator solution consisting of 6 mg N-9, 1000 mg NaCl, 500 mg Na 2 CO 3 , 200 ⁇ l 8 M NaOH in 40 ml H 2 O.
  • the cellophane is left in the indicator solution for 30 minutes.
  • the cellophane is removed from the indicator solution and washed several times with deionized water, whereafter it is left in deionized water at least through the night before use.
  • the prepared membrane is then kept in deionized water until use.
  • Fig. 9 shows a prototype of an optical unit 30 for use in determination of pH in a blood sample.
  • the blood sample is located in the measuring chamber 3011 in the sample container 3000, which is secured between a stationary part 305 and a moving part 306.
  • the previously mentioned membrane with immobilized pH-indicator is provided in the measuring chamber.
  • the blood is pressed away from the measuring chamber by pressing the moving part 306 against the adjacent wall of the measuring chamber 3011. Pressing out the blood sample from the measuring chamber results in the transmission conditions inside the measuring chamber not being influenced by the blood sample itself.
  • the optical unit 30 works in following way: A radiation source 301 in the form of a halogen lamp with a built-in lens of the type LNS-SE6-560 from Hamai Electric Lamp Co. TTD, Tokyo, Japan emits a parallel beam of broad-banded radiation. This radiation is transmitted to a heat absorbing filter 302 of the type KG 5 from Schott, Mainz, West Germany. This filter eliminates radiation from the infrared range. The radiation is transmitted from the filter to a depolarizer 303 and from there through the measuring chamber 3011. A silicon photodiode 304 of the type SFH 212 from Siemens, Kunststoff, West Germany, receives radiation reflected from different surfaces inside the optical unit and is coupled to the radiation source 301 and ensures constant radiation inten- sity from this.
  • the radiation After passage of the measuring chamber 3011, the radiation is focused by a lens 307 ( ⁇ 12 mm; f 12 mm; Ther- mooptik Arnold GmbH & Co., Weilburg, West Germany) onto three silicon photodiodes 310, 313 and 315, which are all of the type SFH 212 and situated in the focal plane of the lens 307. From the lens 307 the radiation is transmitted to a dichroic mirror 308 reflecting radiation of wavelengths less than 560 mm and transmitting radiation of longer wavelengths. The dichroic mirror is delivered by Optisk Laboratorium, Technical University of Denmark, Lyngby, Denmark.
  • the short-waved part of the radiation passes through a band-pass filter 309 (centre value 458 nm; half band width 5.1 nm; Ferroperm, Vedbaek, Denmark) and is transmitted from the band-pass filter 309 to a silicon photodiode 310 of the type SFH 212.
  • the part of the radiation from the lens 307 transmitted through the dichroic mirror 308 is transmitted to another dichroic mirror 311 reflecting radiation of wavelengths less than 690 nm and transmitting the more long-waved radiation.
  • the dichroic mirror is again delivered by Optisk Laboratorium, Technical University of Denmark, Lyngby, Denmark.
  • the reflected radiation is transmitted from the dichroic mirror 311 through a bandpass filter 312 (centre value 589 nm, half band width 14.8 nm; Ferroperm, Vedbaek, Denmark) and from there to a silicon photodiode 313 of the type SFH 212.
  • the radiation transmitted through the dichroic mirror 311 is transmitted from here to a bandpass filter 314 (centre value 750 nm; half band width 10 nm; Ferroperm, Vedbaek, Denmark) and from there to a silicon photodiode 315 of the type SFH 212.
  • the silicon photodiodes 310, 313 and 315 emit a current signal representing the intensity of 458 nm, 589 nm and 760 nm radiation, respectively. On the basis of these radiation intensities the pH value of the sample is calculated.
  • a measurement, ⁇ is determined, whereupon the "true" absorbance at the wavelength ⁇ is determined as
  • a ⁇ A measurement, ⁇ - A background, ⁇ ,
  • the absorbances A ⁇ l and A ⁇ 2 are corrected with A ⁇ 3 , and the "new" absorbance values are designated A' ⁇ 1 and A' ⁇ 2 .
  • the constants k 11 , k 12 , k 21 , and k 22 are determined by measuring A ⁇ 1 , A ⁇ 2 and A ⁇ 3 with two PH
  • the measuring chamber preferably has a volume of 1 - 50 pi, more preferably 5 - 25 pi and in particular 7 - 12 pi and that the initial distance between the the transparent wall parts of the measuring chamber before the drainage for blood sample is preferably less than 1 mm, in particular 200 - 700 pm. Further, is noted that after drainage a distance between the transparent wall parts in the region of the radiation transmission path is preferably 5 - 600 ⁇ pm, in particular 8 - 300 um and most preferably 10 - 200 pm.

Abstract

The method is a method of photometric in vitro determination of the content of an analyte in a sample of whole blood. The blood sample is transferred from an in vivo locality directly to the sample container of a sampling device. The sample container comprises a measuring chamber wherein there is provided a transparent body the radiation transmission characteristics of which vary with the content of analyte in the environment of the body. The transparent body is equilibrated with the sample and thereafter the measuring chamber is deformed in a controlled manner while the portion of the measuring chamber located in the radiation transmission path is drained for blood sample. The analyte content is determined on the basis of detection of the radiation transmitted from the radiation source through the deformed measuring chamber and the transparent body and to the radiation detector. A sampling device and an analyzer for use in photometric in vitro determination of the content of an analyte in a blood sample is also described.

Description

A METHOD OF PHOTOMETRIC IN VITRO DETERMINATION OF THE CONTENT OF AN ANALYTE IN A SAMPLE OF WHOLE BLOOD
The present invention relates to a method of photometric in vitro determination of the content of an analyte in a sample of whole blood as set forth in the introductory part of claim 1.
A number of clinical chemistry analyzers exists which analyzers consist of a combination of disposable components, which are only used for one single analysis operation and only get in touch with one single sample, and an analysing section adapted for receiving the sample containing disposable device and containing the additional components necessary for accomplishing a clinical chemical analysis.
These analyzers all have in common that the transfer of blood sample from patient to disposable device takes place via a separate sampling device such as a syringe, a capillary tube or a vacuum tube sampling device.
In certain cases the sampling device and the disposable device constitute one and the same device. Thus, International patent application WO 86/00138 (Shanks et al.) discloses a device with a cavity sufficiently small for a given sample to be sucked into the cavity by capillary effect. In this equipment the cavity is provided with an electrode structure and possibly a coating of a material adapted to the analysis to be performed with the equipment. The electrode structure provided in the cavity may i.a. be a potentiometric ion sensitive electrode structure or an amperometric electrode structure. The latter is described in connection with determination of hydrogen peroxide and oxygen in the sample.
Supplementary use of the equipment for optical analysis of the products of a specific binding reaction is also described.
From the specification of Danish patent publication DK 150804 (Lilja, J.E. and Nilsson, S.E.L.) is known a sample container for sampling, mixing a sample with at least one reagent and directly performing a separate optical analysis of the sample mixed with the reagent. The sample container has a capillary cavity coated with a reagent and the inlet to the sample container works by capillary effect. The sample container is stated to be useful for most different kinds of analysis and to be especially advantageous for determination of hemoglobin.
From the specification of British patent application GB 2025065 (Meiattini, F. et. al.) is known a plunger syringe for withdrawal of a blood sample. The blood sample is analysed by means of sensors incorporated in the syringe plunger. It is thereby avoided to transfer the sample to a sample station. The sensors are adapted for connection with an analyzer via conductors for registrating, processing, and outprinting analysis data. The specific sensors described in the specification of the said British patent application GB 2025065 are electrochemical sensors for blood gases and blood electrolytes.
None of the above-mentioned publications which in applicant's opinion represent the prior art closest to the present invention deal with the special problems connected with photometric determination of an analyte in whole blood. A serious problem when performing a photometric analysis of a particular analyte in whole blood is that the light reduction caused by the remaining components in the sample is extensive as compared to the light reduction attributable to the analyte. Another serious problem is that due to its content of blood cells whole blood gives rise to a light reduction depending on the content of blood cells in the sample, i.e. of the sample hematocrit, and accordingly said light reduction will constitute an unknown factor. Varying content of other components than hematocrit may also result in a light reduction which varies between samples.
The object of the invention is to provide a method by which the above-mentioned problems connected with photometric analysis of a whole blood sample located in the sample container of a sampling device during the analysis procedure, are readily eliminated. This is achieved by the method according to the invention which method is characterized by the characteristic features of claim 1.
"In vivo locality" denotes in the present context a lo- cality being in direct connection with the blood circulation or being a locality in the blood circulation itself. Sampling by arterial puncture, whereby the blood sample is transferred from the artery to the sample container by a thin needle, as well as via an arterial catheter or via capillary puncture are sampling methodologies, in which the blood sample is transferred directly from an in vivo locality to a sample container.
The radiation emitted from the radiation source may be broad banded as well as monochromatic radiation and may belong to the ultraviolet range, the visible range, the near infrared range and/or the infrared range. The radiation source may comprise one component or several components emitting radiation at their respective particular wavelength range. The radiation detector as well may comprise one component detecting radiation at a particular wavelength range or several components detecting radiation at their respective particular wavelength ranges. The several components of the radiation source may be provided as one integrated device or as separate devices. The same applies to the radiation detector.
The controlled deformation of the sample chamber is a deformation reducing the volume of the measuring chamber to such extent that the measuring chamber is either completely or locally drained for blood sample. By "local draining" is understood that the part of the measuring chamber traversed by the radiation is drained for blood sample. In a preferred embodiment of the method according to the invention the optical communication is established by placing the sample container in a sample container station of an analyzer. Alternatively, the optical communication may be established by one or several cables which via means for contacting the sample container and optical fibres establish optical communication between the optical system and the sample container.
The transparent body used in the method according to the present invention is made of a material with a homegeneous structure, in particular a homogeneous surface making the material suited" for use in photometric transmission analysis. Preferably, the body is shaped as a disc or plate with two planoparallel surfaces and a thickness of less than 1 mm, preferably 1-500 urn, in particular 5-250 um and most preferably 8-200 um.
If an indicator is fixed to the transparent body the indicator may be fixed by any suitable immobilization method such as by absorption, adsorption, ion binding or covalent binding.
Conceivably, it will be possible to make a determination of the content of several analytes in the blood sample within one measuring chamber provided that each individual analyte has an effect on the transmission properties of the transparent body and that each analyte affects the transmission properties differently.
Such determination of several analytes within one measuring chamber may be accomplished by using a transparent body to which several indicators are fixed. The use of a transparent body containing a reagent which on reaction with the analyte forms a reaction product changing the transmission properties of the body in relation to the analyte concentration in the environment of the body would be suitable for the determination of certain analytes. In that case it may be the reaction product per se which changes the transmission properties of the body or an indicator which is fixed to the body and is affected by the reaction product. In particular, the method according to the invention aims at such analytes as blood gases, cationic and anionic components in blood (blood electrolytes), metabolites, hormones, enzymes, proteins, drugs and other chemical species which is or may be found in blood. Examples of such analytes are oxygen, carbon dioxide, H+ (or pH),
Li+, Na+, K+, Ca++, Mg++, Cl-, HCO-3, urea, glucose, creatinine, lactate, bilirubin, cholesterol, triglycerides, and uric acid. Beyond this the invention particularly aims at any analyte mentioned in Mosbach, K. , "Methods in Enzymology, Immobilized Enzymes and
Cells, Part D", 137 (1988) p. 4-7 and ibid., p. 411.
In connection with determination of the carbon dioxide content is preferred a body made of silicone rubber or another transparent, homogeneous material with a high dissolution power for CO2. The CO2 determination is accomplished on the basis of testing the transmission properties of the body for 4.2 um radiation. The basic principles for such determination are disclosed in the specification of British patent application GB 2160646 and in the specification of European patent application EP 253559.
In connection with determination of pH is preferred a body made of a polymer material with -OH groups available for immobilization, e.g. a cellulose or cellophane material, and with a pH indicator which may be covalently bound thereto, e.g. an indicator comprising the reactive group -SO2-CH2-CH2-O-SO3H. Cellophane in particular has physical properties suitable for the present purpose, such as a well-defined thickness and a homogeneous structure.
The invention also relates to a sampling device comprising a sample container with a measuring chamber having at least locally transparent opposite wall parts and having the characteristic features set forth in the characterizing part of claim 11.
Preferably, the locally transparent wall parts comprise planoparallel parts extending parallel with the planoparallel surfaces of the transparent body. By such configu ration is ensured that the drainage of the measuring chamber is readily obtained, viz. by pressing the wall parts against the transparent body. The transparent body may be loosely accomodated in the measuring chamber or it may be fixed to a wall part.
Other preferred embodiments of the sampling device according to the invention have the characteristic features set forth in the dependent claims.
The sample container may comprise one measuring chamber or several measuring chambers disposed in series or in parallel. Preferably the sample container is made of an injection mouldable polymeric base material, e.g. the material sold under the trade name ARNITE™ from AKZO, Arnheim, Holland.
In connection with the performance of a pH or a carbon dioxide determination on a blood sample in the measuring chamber the wall parts of the measuring chamber are preferably made of a polymer material having a low carbon dioxide permeability and suitable transmission properties for radiation at the wavelengths relevant to the abovementioned determinations, said wavelengths being discussed at another page. A suitable material is an ethylene vinylalcohol copolymer of the type EVAL-E T™ sold by
Kuraray Co., Osaka, Japan.
In the case where the blood sample is provided by capillary puncture, the use of a sample container with a dimension sufficiently small for the sample container to be filled by capillary effect is preferred.
In the case where a sample of arterial blood is desired, the use of a sample container with an inlet located in a coupling means, preferably a Luer cone, for coupling the sample container to a needle or a catheter is preferred.
The invention further comprises an analyzer for use in the method according to the invention, said analyzer having the characteristic features set forth in the characterizing part of claim 21.
In a preferred embodiment the analyzer comprises data processing means for processing the registered radiation data for deriving the content of the actual analyte in the actual sample from these. Alternatively the analyzer is adapted for connection to a separate data processing unit.
In a further preferred embodiment of the system according to the invention the analyzer comprises means for displaying the analyte content. Alternatively, the analyzer is adapted for connection with means such as, e.g. a data screen, a display, a printer, or a plotter.
The invention will now be explained in the following with reference to the drawings and the subsequent examples. In the drawings
Fig. 1 is a perspective view of a preferred embodiment of an analyzer and a sample container, which together constitute the system according to the invention for photometric in vitro determination of an analyte in a blood sampler
Fig. 2 is an enlarged schematic view from above of the sample container station of the analyzer with the sampling device; Fig. 3, Fig. 4 and Fig. 5 are views of a preferred embodiment of a sampling device according to the invention;
Fig. 6 is an electric block diagram of the analyzer shown in Fig, 1;
Fig. 7 shows the photometric basis for determination of pH; Fig. 8 is a perspective view of a sample container for use in determining pH;
Fig. 9 is a partial cross section of an optical unit in a system comprising an analyzer according to the invention and a sampling device according to the invention for photometric determination of pH and with a schematic representation of the components forming parts of the optical unit; In the different figures like reference numerals designate like parts.
The analysis system shown in Fig. 1 and generally designated 10 is a compact portable "stand-alone" system, which is suited for decentral use, i.e. use outside a regular laboratory environment, e.g. in an operating room or at an intensive ward. The analysis system 10 comprises a blood sampling device 2 for disposable use and used in connection with an analyzer 11. The sampling device 2 is more explicitly described in connection with the description of Fig. 3-5 below. The sample container 2 and the analyzer 11 are adapted to interact in the way that the analyzer 11 has a sample container station 1 with an optical section 3 adapted for receiving the sampling device 2 or possibly the sample container of the sampling device, so that the optical communication between the sampling device 2 and the optical components of the optical unit 3, which is necessary for photometric analysis, is obtained. The sample container station 1 can be closed by a cover
8, which is closed after placing the sampling device 2 in the station. By closing the cover 8 different mechanisms are activated, e.g. a not shown clamping mechanism, which secures the sampling device 2 in the optical section 3 and at the same time thermostatically controls the sampling device to a desired temperature, preferably app. 37ºC.
Closing the cover 8 further results in a signal being sent to the controlling unit of the analyzer and indieating the start of an analysis procedure. An operator can control the operation of the analyzer by means of a keyboard 5 and a display 6. The analyzer 11 preferably also comprises a printer, which can produce an outprint 7 of i.a. the analysis results obtained by the analyzer.
After placing the sampling device 2 in the sample container station 1 and closing the cover 8 of this, the optical components comprising of radiation sources and radiation detectors are activated, whereupon the ana- lyzer 11 calculates one or several parameters on the basis of the signals from the radiation detectors. The result of the calculations is displayed on the display 6 and is printed on the paper outprint 7 by the printer. When the calculations are terminated and the results displayed and/or printed out the cover 8 is opened and the sampling device 2 is displaced from the sample container station 1 and disposed of.
In a larger scale Fig. 2 shows a partially schematic section of the sample container station 1 viewed from above. As shown the optical section 3 comprises four optical units 30, 40, 50, and 60 adapted for determination of pH (unit 30), carbon dioxide (unit 40), oxygen (unit 50) and hemoglobin and oxygen saturation (unit 60) respectively. The sample container of the sampling device with four measuring chambers is placed in a slot 4 in the optical section 3.
Even though the analyzer 11 is shown containing four optical units it can in principle contain an arbitrary number and/or an arbitrary combination of units beyond the unit utilized in the method according to the invention.
Fig. 3 shows a longitudinal section of the sampling device 2 and four segments of this in a larger scale. The sampling device comprises a body 23, which at least in specified areas is made of a material transparent for the relevant radiation. The body 23 has a continuous conduit 22 locally extended for forming measuring chambers 300, 400, 500, and 600. During a course of measurement the actual blood sample fills the conduit 22 from its inlet aperture 21 to a hydrophobic filter 24 placed behind the measuring chambers. The section of the body 23 surrounding the inlet aperture is provided with a Luer cone and is therefore suitable for being mounted with a needle 20 of the type normally used for blood sampling. The section 25 of the body 23 pointing away from the inlet aperture is adapted for coupling with a traditional plunger syringe. Such a plunger syringe is used as aid at the sampling in certain situations, e.g. when the patient, whose blood gas parameters are to be determined, has a very low blood pressure.
When the sampling device 2 is placed correctly in the sample container station 1, the measuring chambers 300, 400, 500, and 600 communicate optically with the optical units 30, 40, 50, and 60. The measuring chamber 300 optically communicating with the optical unit 30 is adapted for determination of pH in the blood sample and contains a cellophane membrane 316, to which is immobilized a pH absorbance indicator. When the indicator is in chemical equilibrium with the blood sample, the ratio between the acid form of the indicator and the basic form of the indicator reflects the pH value of the blood sample. The chemical and photometric basis for the pH determination appears from Fig. 7, 8, and 9 and of the description of these. An embodiment of the optical unit 30 appears from fig. 9 and the description of this.
Finally it appears from Fig. 3 that the sampling device 2 has an integral needle protecting means 26. In the embodiment shown the needle protecting means 26 is a tubular jacket movable in the axial direction of the sample container between a first position, wherein the jacket exposes the point of the needle, and a second position, wherein the jacket surrounds the point of the needle.
Fig. 3 shows the protecting jacket 26 in the first position, in which it is placed at the sampling moment. Fig. 4 shows a longitudinal section of the sampling device. The section is placed perpendicular to the section shown in Fig. 3.
The sample container body 23 consists of two halves, of which only one is seen in Fig. 4.
Fig. 5 shows finally the same section as Fig. 3 but in Fig. 5 the protecting jacket is displaced to the second position, wherein it surrounds the point of the needle. The jacket 26 is displaced to this second position immediately after the sampling. Fig. 6 shows the electrical block diagram for the analyzer 11 and speaks for itself.
Fig. 7 shows the absorption spectrum for a pH absorption indicator N-9 more closely described below in connection with Fig. 8. The indicator is immobilized to a cellophane membrane by the method also described in detail in connection with Fig. 8. The spectrum is recorded by a spectrophotometer of the type Shimadzu Spectrophotometer UV 250. The absorption measurements were performed on a cellophane membrane (6 × 12 × 0.028 mm) with immobilized indicator. The cellophane was placed in the cuvette of the spectrophotometer in a holder adapted thereto and with dimensions adapted to the dimensions of the cuvette.
In order to determine the absorption conditions at different pH-values, a number of pH buffers with pH values in the pH range from pH 6.14 - 11.74 was produced. Each buffer consisted of 500 ml 0.1 M KH2PO4 to which was added the necessary amount of 0.1 M NaOH. The pH value of each buffer was potentiometrically measured (Radiometer PHM80) by means of a glass electrode (Radiometer GK2402C).
It appears from the spectrum shown in Fig. 7 that the acid form of the indicator has an absorption top at 458 nm and that the basic form of the indicator has an absorption top at 595 nm and that the indicator not substantially absorbs radiation at wavelengths above 750 nm. Fig. 8 shows an embodiment of a sample container for use in determination of pH in a blood sample. The sample container generally designated 3000, is intended to interact with an analyzer with an optical unit as the one more closely described below in connection with Fig. 9. The sample container consists of two halves 3001 and 3002.
These halves are made from a transparent plastic materi al, e.g. softened polymethyl methacrylate of the type DE- GALAN™ SZ70 (Superfos, Copenhagen, Denmark). The two halves are assembled by pins 3005 and 3006 in the half 3001 engaging corresponding, not shown recesses in the half 3002, while not shown pins in this engage recesses 3007 and 3008 in the half 3001. The two halves are hereafter welded together by ultrasonic welding. The line 3009 of material outlined on the lower half 3001 shown in the figure forms a welding seam after the welding. This line of material lies along the edge of a longitudinal conduit 3004, which centrally expands transversely and forms a measuring chamber 3011. A wall section 3010 of the upper half 3002 shown in the figure is elastically deformable and for that reason has a very reduced wall thickness compared to the rest of the half. As mentioned in connection with Fig. 7 a cellophane membrane 3003, to which there is immobilized a pH indicator, is placed in the measuring chamber 3011.
Preparation of the Cellophane Membrane with Immobilized pH Indicator
The pH indicator is delivered by Merck, Darmstadt, West Germany under the name N-9 and is known to contain the reactive group
-SO2-CH2-CH2-O-SO3H.
The immobilisation of the indicator to the membrane takes place in a process, whereby the above mentioned reactive group is transformed with sodium hydroxide into a vinyl sulphone group, which can be coupled to cellophane previously activated by conditioning the cellophane in 0.1 M NaOH for 15 minutes. The reaction scheme describing the coupling reaction between the indicator and the cellophane membrane is:
R-SO2-CH2-CH2-O-SO3H + 2 NaOH
(1)
R-SO2-CH=CH2 + Na2SO4 + 2 H2O
R-SO2-CH=CH2 + HO-cellophane
R-SO2-CH2-CH2-O-cellophane (2)
R here designates an aryl group.
The quantitative immobilisation procedure is the following :
100 mg cellophane (of the type 113650 - 36/32 from
Struers, Copenhagen, Denmark) is after the above mentioned conditioning with NaOH prepared with an indicator solution consisting of 6 mg N-9, 1000 mg NaCl, 500 mg Na2CO3, 200 μl 8 M NaOH in 40 ml H2O. The cellophane is left in the indicator solution for 30 minutes. Hereafter the cellophane is removed from the indicator solution and washed several times with deionized water, whereafter it is left in deionized water at least through the night before use. The prepared membrane is then kept in deionized water until use.
Fig. 9 shows a prototype of an optical unit 30 for use in determination of pH in a blood sample. The blood sample is located in the measuring chamber 3011 in the sample container 3000, which is secured between a stationary part 305 and a moving part 306. The previously mentioned membrane with immobilized pH-indicator is provided in the measuring chamber. Before the measuring, the blood is pressed away from the measuring chamber by pressing the moving part 306 against the adjacent wall of the measuring chamber 3011. Pressing out the blood sample from the measuring chamber results in the transmission conditions inside the measuring chamber not being influenced by the blood sample itself.
The optical unit 30 works in following way: A radiation source 301 in the form of a halogen lamp with a built-in lens of the type LNS-SE6-560 from Hamai Electric Lamp Co. TTD, Tokyo, Japan emits a parallel beam of broad-banded radiation. This radiation is transmitted to a heat absorbing filter 302 of the type KG 5 from Schott, Mainz, West Germany. This filter eliminates radiation from the infrared range. The radiation is transmitted from the filter to a depolarizer 303 and from there through the measuring chamber 3011. A silicon photodiode 304 of the type SFH 212 from Siemens, Munich, West Germany, receives radiation reflected from different surfaces inside the optical unit and is coupled to the radiation source 301 and ensures constant radiation inten- sity from this.
After passage of the measuring chamber 3011, the radiation is focused by a lens 307 (ø 12 mm; f 12 mm; Ther- mooptik Arnold GmbH & Co., Weilburg, West Germany) onto three silicon photodiodes 310, 313 and 315, which are all of the type SFH 212 and situated in the focal plane of the lens 307. From the lens 307 the radiation is transmitted to a dichroic mirror 308 reflecting radiation of wavelengths less than 560 mm and transmitting radiation of longer wavelengths. The dichroic mirror is delivered by Optisk Laboratorium, Technical University of Denmark, Lyngby, Denmark. The short-waved part of the radiation passes through a band-pass filter 309 (centre value 458 nm; half band width 5.1 nm; Ferroperm, Vedbaek, Denmark) and is transmitted from the band-pass filter 309 to a silicon photodiode 310 of the type SFH 212. The part of the radiation from the lens 307 transmitted through the dichroic mirror 308 is transmitted to another dichroic mirror 311 reflecting radiation of wavelengths less than 690 nm and transmitting the more long-waved radiation. The dichroic mirror is again delivered by Optisk Laboratorium, Technical University of Denmark, Lyngby, Denmark. The reflected radiation is transmitted from the dichroic mirror 311 through a bandpass filter 312 (centre value 589 nm, half band width 14.8 nm; Ferroperm, Vedbaek, Denmark) and from there to a silicon photodiode 313 of the type SFH 212. The radiation transmitted through the dichroic mirror 311 is transmitted from here to a bandpass filter 314 (centre value 750 nm; half band width 10 nm; Ferroperm, Vedbaek, Denmark) and from there to a silicon photodiode 315 of the type SFH 212. The silicon photodiodes 310, 313 and 315 emit a current signal representing the intensity of 458 nm, 589 nm and 760 nm radiation, respectively. On the basis of these radiation intensities the pH value of the sample is calculated.
More precisely the pH value of the sample is calculated in the following way:
With different samples in the form of blood sample as well as the below mentioned two pH buffers in the sample container is for each wavelength λ1, λ2, λ3 determined the current Ibackground, λ measured on the corresponding photodiode for a sample container containing a cellophane membrane without immobilized indicator (i.e. a clear cellophane membrane) and sample. This current corresponds to IO (cf. Lambert Beer's Law).
From the knowledge of the dynamic range of the amplifier for the individual photodiode the current Ibackground, λ can be related to the absorbance Abackground, λ , as Abackground, λ = k · log Ibackground, λ where k is a constant.
In the measuring situation where the sample container contains a cellophane membrane prepared with pH indicator, the current Imeasurement, λ also relating to
Ameasurement, λ is determined, whereupon the "true" absorbance at the wavelength λ is determined as
Aλ = Ameasurement, λ - Abackground, λ,
cf. A = log I - log IO.
To correct further for drift in the optical system, unclear sample containers or other variations not directly relating to the pH determination, the absorbances Aλl and Aλ2 are corrected with Aλ3, and the "new" absorbance values are designated A'λ1 and A'λ2.
The relation to Lambert Beer's Law hereafter appears as : A'λ1 = Aλl - Aλ3 = ελ1,HIn·cHIn·1 + ελl,In-·cln-·1
(3) A'λ2 = Aλ2 - Aλ3 = ελ2,HIn·cHIn·1 + ελ2, In-·cln-·1 where HIn designates the acid form of the pH indicator.
In designates the basic form of the indicator, cHIn and cIn- the concentration of the acid and the basic form, respectively, of the indicator, s the extinction coefficient for the wavelength and compound defined by the suffix, and 1 the pathlength of the radiation
through the sample, which can be inverted to: cHIn = k11 A'λ1 + k12 A'λ2
(4) cIn- = k21 A'λ1 + k22 A'λ2
The constants k11, k12, k21, and k22 are determined by measuring Aλ1, Aλ2 and Aλ3 with two PH
buffers with known pH values as samples. For each of these pH buffers the proportion cIn-/cHIn is determined according to the Henderson Hasselbalch equation: pH - pka + log[cIn-/cHIn] (5)
Is it further supposed that cIn - + cHIn = 1, the two sets of connected values of cIn- and cHln can be
calculated. If the corrected absorbance values are inserted in the equation set (4), four equations with the four unknown quantities k11, k12, k21, and k22
are obtained, and subsequently these four quantities can be calculated.
By measuring unknown samples it is hereafter possible to determine cHIn and cIn- from the equation set (4) and subsequently pH from equation (5).
With respect to the dimensions of the sampling device is noted that the measuring chamber preferably has a volume of 1 - 50 pi, more preferably 5 - 25 pi and in particular 7 - 12 pi and that the initial distance between the the transparent wall parts of the measuring chamber before the drainage for blood sample is preferably less than 1 mm, in particular 200 - 700 pm. Further, is noted that after drainage a distance between the transparent wall parts in the region of the radiation transmission path is preferably 5 - 600 ^pm, in particular 8 - 300 um and most preferably 10 - 200 pm.

Claims

C L A I M S
1. A method of photometric in vitro determination of the content of an analyte in a sample of whole blood wherein the sample from an in vivo locality is transferred directly to a sampling device comprising a measuring chamber with at least locally transparent wall parts and the sample containing sample container is brought into optical communication with an optical system adapted to the analyte and comprising a radiation source and a radiation detector arranged downstreams to the sample container in the radiation transmission path, c h a r a c t e r i z e d in,
that there is provided within the measuring chamber a transparent body, the transmission characteristics of which for radiation transmitted through the sample container vary with the content of analyte in the environment of the body, that the body is equilibrated with the sample, that subsequently the measuring chamber is deformed in a controlled manner thereby providing a substantially complete draining of blood sample from the part of the measuring chamber located in the radiation transmission path, and that the analyte content is determined on the basis of detection of radiation transmitted from the radiation source through the deformed measuring chamber and the transparent body and to the radiation detector.
2. A method according to claim 1,
c h a r a c t e r i z e d in,
that there is used a sampling device, wherein the transparent body has two planoparallel surfaces arranged perpendicular to the transmission direction.
3. A method according to claim 1,
c h a r a c t e r i z e d in,
that there is used a sampling device, wherein the locally transparent wall parts of the measuring chamber comprise planoparallel parts extending parallel to the planoparallel surfaces of the transparent body.
4. A method according to claims 1 - 3,
c h a r a c t e r i z e d in,
that the analyte is a blood electrolyte, and that there is used a sampling device with a transparent body having fixed thereto an indicator, the radiation absorption characteristics of which vary with the content of the particular analyte in the sample.
5. A method according to claim 4,
c h a r a c t e r i z e d in,
that the analyte is a cationic blood component, such as H+, Li+, Na+, K+, Ca++, Mg++.
6. A method according to claim 5,
c h a r a c t e r i z e d in,
that the analyte is H+, and that the indicator is a pH-indicator having a pronounced pH sensitivity at physiological blood pH values.
7. A method according to claim 6,
c h a r a c t e r i z e d in,
that the pH indicator is covalently bound to the transparent body.
8. A method according to claim 7,
c h a r a c t e r i z e d in,
that the transparent body is provided from a polymer material comprising -OH groups available for immobilization, e.g. a cellulose or cellophane material.
9. A method according to claims 5 - 8,
c h a r a c t e r i z e d in,
that the pH indicator is a compound comprising the functional group -SO2-CH2-CH2-O-SO3H.
10. A method according to claims 1 - 3,
c h a r a c t e r i z e d in,
that the analyte is CO2 and that the transparent body is provided from a transparent material having a high dissolution power for CO2, e.g. silicone rubber.
11. A sampling device comprising a sample container with a measuring chamber with at least locally transparent opposite wall parts,
c h a r a c t e r i z e d in,
that there is provided within the measuring chamber a transparent body the radiation transmission characteristics of which vary with the content of a particular analyte in the environment of the body, and that the measuring chamber is deformable in a controlled manner and such that it locally can be substantially drained for sample.
12. A sampling device according to claim 11,
c h a r a c t e r i z e d in,
that the transparent body has two planoparallel surfaces.
13. A sampling device according to claim 12,
c h a r a c t e r i z e d in,
that the locally transparent wall parts of the mea- suring chamber comprise planoparallel parts extending parallel to the planoparallel surfaces of the transparent body.
14. A sampling device according to claims 11 - 13,
c h a r a c t e r i z e d in,
that one of the locally transparent wall parts is so deformable that it can be brought into abutment with the transparent body while expulsing any intermediate sample portion.
15. A sampling device according to claim 14,
c h a r a c t e r i z e d in,
that both locally transparent wall parts are so deformable that they can be brought into abutment with the transparent body while expulsing any intermediate sample portions.
16. A sampling device according to claim 14,
c h a r a c t e r i z e d in,
that the locally transparent wall part is so deformable that it can be brought into abutment with the transparent wall part while expulsing any intermediate sample portion and that simultaneously the transparent body is brought into abutment with the opposite locally transparent wall part while expulsing any sample portion located between the body and the latter wall part.
17. A sampling device according to claims 14 - 16,
c h a r a c t e r i z e d in,
that to the transparent body there is fixed an indicator, the radiation absorption characteristics of which vary with the content of the particular analyte.
18. A sampling device according to claims 11 - 17,
cha r a c t e r i z e d in,
that the transparent body is provided from a polymer material comprising -OH groups available for immobilization, e.g. a cellulose or cellophane material.
19. A sampling device according to claims 11 - 18, c h a r a c t e r i z e d in,
that the indicator is a pH-indicator having a pronounced pH sensitivity at physiological blood pH values.
20. A sampling device according to claims 11 - 16,
c h a r a c t e r i z e d in,
that the transparent body is provided from a transparent material having a high dissolution power for CO2, e.g. silicone rubber.
21. An analyzer comprising a radiation souce, a radiation detector and a sample container station so arranged relatively to the radiation source and the radiation detector that a sample container arranged within the sample container station and comprising a measuring chamber with locally transparent wall parts is located within the radiation transmission path from the radiation source to the radiation detector,
c h a r a c t e r i z e d in,
that in the analyzer there is provided means at the sample container station which means on activation are adapted to deform in a controlled manner the measuring chamber of a sample container arranged in the sample container station and that way that the measuring chamber part located in the radiation transmission path is essentially drained for blood sample .
22. An analyser according to claim 21 ,
c h a r a c t e r i z e d in,
that the analyzer is adapted to cooperate with a sample container comprising a transparent body, and that the means for controlled deformation of the measuring chamber cooperate with a wall part of the measuring chamber and displace and deform said wall part that way that the wall part is brought into abutment with a surface of the transparent body and the opposite surface of the transparent body is brought into abutment with the opposite wall part of the measuring chamber while any intermediate blood sample portions are expulsed from the radiation transmission path.
PCT/DK1989/000301 1988-12-22 1989-12-21 A method of photometric in vitro determination of the content of an analyte in a sample of whole blood WO1990007109A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE68918292T DE68918292T2 (en) 1988-12-22 1989-12-21 IN VITRO PHOTOMETRIC METHOD FOR DETERMINING THE CONTENT OF ANALYTE IN A WHOLE BLOOD SAMPLE.
JP2501614A JPH0833390B2 (en) 1988-12-22 1989-12-21 Method for optical in vitro determination of analyte content in whole blood samples
EP90900767A EP0534945B1 (en) 1988-12-22 1989-12-21 A METHOD OF PHOTOMETRIC $i(IN VITRO) DETERMINATION OF THE CONTENT OF AN ANALYTE IN A SAMPLE OF WHOLE BLOOD
DK911092A DK109291D0 (en) 1988-12-22 1991-06-07 METHOD OF PHOTOMETRIC IN VITRO DETERMINING THE CONTENT OF AN ANALYTE IN A SAMPLE OF FULL BLOOD

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK716288A DK163194C (en) 1988-12-22 1988-12-22 METHOD OF PHOTOMETRIC IN VITRO DETERMINING A BLOOD GAS PARAMETER IN A BLOOD TEST
DK7162/88 1988-12-22

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WO1990007109A1 true WO1990007109A1 (en) 1990-06-28

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PCT/DK1989/000301 WO1990007109A1 (en) 1988-12-22 1989-12-21 A method of photometric in vitro determination of the content of an analyte in a sample of whole blood
PCT/DK1989/000300 WO1990007107A1 (en) 1987-11-25 1989-12-21 A method of photometric in vitro determination of the content of oxygen in a blood sample
PCT/DK1989/000302 WO1990007106A1 (en) 1988-12-22 1989-12-21 A method of photometric in vitro determination of a blood gas parameter in a blood sample

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PCT/DK1989/000302 WO1990007106A1 (en) 1988-12-22 1989-12-21 A method of photometric in vitro determination of a blood gas parameter in a blood sample

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993006456A1 (en) * 1991-09-19 1993-04-01 Radiometer A/S Method of photometric in vitro determination of the content of an analyte in a sample
EP0539035A2 (en) * 1991-09-30 1993-04-28 Ortho Pharmaceutical Corporation Apparatus and method for measuring a bodily constituent

Families Citing this family (171)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2143365A1 (en) * 1994-03-14 1995-09-15 Hugh V. Cottingham Nucleic acid amplification method and apparatus
US5504011A (en) * 1994-10-21 1996-04-02 International Technidyne Corporation Portable test apparatus and associated method of performing a blood coagulation test
FR2726911B1 (en) * 1994-11-16 1996-12-27 Laurec Francois Xavier APPARATUS FOR MEASURING AND DISPLAYING AN ALCOHOLIC RATE IN THE EXPIRED ALVEOLAR AIR
AT407303B (en) * 1995-07-17 2001-02-26 Avl Verbrennungskraft Messtech METHOD FOR QUALITY CONTROL OF A PORTABLE ANALYSIS SYSTEM AND LIQUID FOR IMPLEMENTING THE METHOD
US6212424B1 (en) 1998-10-29 2001-04-03 Rio Grande Medical Technologies, Inc. Apparatus and method for determination of the adequacy of dialysis by non-invasive near-infrared spectroscopy
US6240306B1 (en) 1995-08-09 2001-05-29 Rio Grande Medical Technologies, Inc. Method and apparatus for non-invasive blood analyte measurement with fluid compartment equilibration
US6353471B1 (en) 1995-10-10 2002-03-05 Cme Telemetrix Inc. Method and apparatus for non-destructive screening of specimen integrity
AP931A (en) * 1995-10-23 2001-02-02 Cytometrics Inc Method and apparatus for reflected imaging analysis.
US5670375A (en) * 1996-02-21 1997-09-23 Biomerieux Vitek, Inc. Sample card transport method for biological sample testing machine
US5801057A (en) * 1996-03-22 1998-09-01 Smart; Wilson H. Microsampling device and method of construction
US5863460A (en) * 1996-04-01 1999-01-26 Chiron Diagnostics Corporation Oxygen sensing membranes and methods of making same
US5719053A (en) * 1996-05-06 1998-02-17 Primus Corporation Chromatographic method for the identification and characterization of hemoglobin variants in blood
DE69711177T2 (en) 1996-05-30 2002-10-10 Radiometer Medical As Broensho SYSTEM FOR DETERMINING AT LEAST ONE PARAMETER AT LEAST ONE SAMPLE OF A PHYSIOLOGICAL LIQUID, AND CASSETTE THEREFOR
US5885212A (en) * 1996-06-13 1999-03-23 Chiron Diagnostics Corporation Non-invasive measurement of blood PH
AT404513B (en) * 1996-07-12 1998-12-28 Avl Verbrennungskraft Messtech METHOD AND MEASURING ARRANGEMENT FOR THE OPTICAL DETERMINATION OF TOTAL HEMOGLOBIN CONCENTRATION
WO1998019592A1 (en) * 1996-11-01 1998-05-14 Rio Grande Medical Technologies, Inc. Dialysis monitoring method and apparatus
DE19652784A1 (en) * 1996-12-19 1998-06-25 Dade Behring Marburg Gmbh Device (cuvette) for holding and storing liquids and for carrying out optical measurements
US5853666A (en) * 1997-02-12 1998-12-29 Biomerieux Vitek, Inc. Optical reader and sample card transport stations for biological sample testing machine
US6995835B2 (en) * 1997-03-03 2006-02-07 Nir Diagnostics Inc. Method and apparatus for measuring analytes in blood bags
US6268910B1 (en) 1997-03-03 2001-07-31 Cme Telemetrix Inc. Method and apparatus for screening plasma for interferents in plasma from donor blood bags
US5846492A (en) * 1997-03-11 1998-12-08 Johnson & Johnson Clinical Diagnostics, Inc. Sample quality measurement and/or analyte measurement in the dispensing tip of an analyzer
CA2231305C (en) * 1997-03-11 2007-03-20 Merrit Nyles Jacobs Improved analyzer throughput featuring through-the-tip analysis
US7890158B2 (en) 2001-06-05 2011-02-15 Lumidigm, Inc. Apparatus and method of biometric determination using specialized optical spectroscopy systems
US6628809B1 (en) 1999-10-08 2003-09-30 Lumidigm, Inc. Apparatus and method for identification of individuals by near-infrared spectrum
US6306347B1 (en) 1998-01-21 2001-10-23 Bayer Corporation Optical sensor and method of operation
US6190612B1 (en) 1998-01-21 2001-02-20 Bayer Corporation Oxygen sensing membranes and methods of making same
US6254831B1 (en) 1998-01-21 2001-07-03 Bayer Corporation Optical sensors with reflective materials
EP0980518B1 (en) * 1998-02-10 2007-03-14 Daedalus I, LLC APPARATUS FOR DETERMINATION OF pH, pCO2, HEMOGLOBIN AND HEMOGLOBIN OXYGEN SATURATION
US6694157B1 (en) 1998-02-10 2004-02-17 Daedalus I , L.L.C. Method and apparatus for determination of pH pCO2, hemoglobin, and hemoglobin oxygen saturation
US6391005B1 (en) 1998-03-30 2002-05-21 Agilent Technologies, Inc. Apparatus and method for penetration with shaft having a sensor for sensing penetration depth
ATE246352T1 (en) 1998-05-13 2003-08-15 Bayer Ag FLOW Cuvette FOR SPECTROSCOPIC EXAMINATION OF A SAMPLE
US6107083A (en) * 1998-08-21 2000-08-22 Bayer Corporation Optical oxidative enzyme-based sensors
US6207110B1 (en) 1998-08-21 2001-03-27 Bayer Corporation Metallic overcoating as a light attenuating layer for optical sensors
US6157041A (en) * 1998-10-13 2000-12-05 Rio Grande Medical Technologies, Inc. Methods and apparatus for tailoring spectroscopic calibration models
US6441388B1 (en) 1998-10-13 2002-08-27 Rio Grande Medical Technologies, Inc. Methods and apparatus for spectroscopic calibration model transfer
US7098037B2 (en) 1998-10-13 2006-08-29 Inlight Solutions, Inc. Accommodating subject and instrument variations in spectroscopic determinations
US6144444A (en) * 1998-11-06 2000-11-07 Medtronic Avecor Cardiovascular, Inc. Apparatus and method to determine blood parameters
US6816605B2 (en) 1999-10-08 2004-11-09 Lumidigm, Inc. Methods and systems for biometric identification of individuals using linear optical spectroscopy
US6375627B1 (en) * 2000-03-02 2002-04-23 Agilent Technologies, Inc. Physiological fluid extraction with rapid analysis
US8518328B2 (en) * 2005-12-27 2013-08-27 Honeywell International Inc. Fluid sensing and control in a fluidic analyzer
US6540675B2 (en) * 2000-06-27 2003-04-01 Rosedale Medical, Inc. Analyte monitor
SE518539C2 (en) * 2000-06-28 2002-10-22 Migrata U K Ltd Method and cuvette for quantitative hemoglobin determination in undiluted whole blood
US8641644B2 (en) 2000-11-21 2014-02-04 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US20060009680A1 (en) * 2001-01-17 2006-01-12 Innon Holdings, Inc. Endoscope valve assembly and method
US7025774B2 (en) 2001-06-12 2006-04-11 Pelikan Technologies, Inc. Tissue penetration device
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7981056B2 (en) 2002-04-19 2011-07-19 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
WO2002100254A2 (en) 2001-06-12 2002-12-19 Pelikan Technologies, Inc. Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
EP1404233B1 (en) 2001-06-12 2009-12-02 Pelikan Technologies Inc. Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties
US7033371B2 (en) 2001-06-12 2006-04-25 Pelikan Technologies, Inc. Electric lancet actuator
US8337419B2 (en) 2002-04-19 2012-12-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7344507B2 (en) 2002-04-19 2008-03-18 Pelikan Technologies, Inc. Method and apparatus for lancet actuation
US9226699B2 (en) 2002-04-19 2016-01-05 Sanofi-Aventis Deutschland Gmbh Body fluid sampling module with a continuous compression tissue interface surface
US7004928B2 (en) * 2002-02-08 2006-02-28 Rosedale Medical, Inc. Autonomous, ambulatory analyte monitor or drug delivery device
US7892183B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7909778B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7892185B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US7229458B2 (en) 2002-04-19 2007-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7232451B2 (en) 2002-04-19 2007-06-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7713214B2 (en) 2002-04-19 2010-05-11 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with optical analyte sensing
US8221334B2 (en) 2002-04-19 2012-07-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
US7331931B2 (en) 2002-04-19 2008-02-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8360992B2 (en) 2002-04-19 2013-01-29 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7976476B2 (en) 2002-04-19 2011-07-12 Pelikan Technologies, Inc. Device and method for variable speed lancet
US8702624B2 (en) 2006-09-29 2014-04-22 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US9795334B2 (en) 2002-04-19 2017-10-24 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7297122B2 (en) 2002-04-19 2007-11-20 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8579831B2 (en) 2002-04-19 2013-11-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7547287B2 (en) 2002-04-19 2009-06-16 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7491178B2 (en) 2002-04-19 2009-02-17 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7620212B1 (en) 2002-08-13 2009-11-17 Lumidigm, Inc. Electro-optical sensor
CA2446328C (en) * 2002-10-29 2013-12-31 Bayer Healthcare Llc Optical reagent format for small sample volumes
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US20040132168A1 (en) * 2003-01-06 2004-07-08 Peter Rule Sample element for reagentless whole blood glucose meter
US8377381B2 (en) 2003-01-21 2013-02-19 Bayer Healthcare Llc Optical format
US7052652B2 (en) * 2003-03-24 2006-05-30 Rosedale Medical, Inc. Analyte concentration detection devices and methods
US7460696B2 (en) 2004-06-01 2008-12-02 Lumidigm, Inc. Multispectral imaging biometrics
US7347365B2 (en) 2003-04-04 2008-03-25 Lumidigm, Inc. Combined total-internal-reflectance and tissue imaging systems and methods
US7539330B2 (en) 2004-06-01 2009-05-26 Lumidigm, Inc. Multispectral liveness determination
US7668350B2 (en) 2003-04-04 2010-02-23 Lumidigm, Inc. Comparative texture analysis of tissue for biometric spoof detection
US7751594B2 (en) 2003-04-04 2010-07-06 Lumidigm, Inc. White-light spectral biometric sensors
AU2004227886A1 (en) 2003-04-04 2004-10-21 Lumidigm, Inc. Multispectral biometric sensor
US7545963B2 (en) 2003-04-04 2009-06-09 Lumidigm, Inc. Texture-biometrics sensor
US7627151B2 (en) 2003-04-04 2009-12-01 Lumidigm, Inc. Systems and methods for improved biometric feature definition
US7394919B2 (en) 2004-06-01 2008-07-01 Lumidigm, Inc. Multispectral biometric imaging
JP2004343275A (en) * 2003-05-14 2004-12-02 Murata Mach Ltd Image processing system and scanner
DE602004028463D1 (en) 2003-05-30 2010-09-16 Pelikan Technologies Inc METHOD AND DEVICE FOR INJECTING LIQUID
US7850621B2 (en) 2003-06-06 2010-12-14 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
WO2006001797A1 (en) 2004-06-14 2006-01-05 Pelikan Technologies, Inc. Low pain penetrating
US8282576B2 (en) 2003-09-29 2012-10-09 Sanofi-Aventis Deutschland Gmbh Method and apparatus for an improved sample capture device
EP1680014A4 (en) 2003-10-14 2009-01-21 Pelikan Technologies Inc Method and apparatus for a variable user interface
CN1875260A (en) 2003-10-30 2006-12-06 拜尔健康护理有限责任公司 Formats for optical analysis and methods of manufacturing the same
US8226904B2 (en) 2003-10-30 2012-07-24 Bayer Healthcare Llc Optical format with platform-and-well construction
US7263213B2 (en) 2003-12-11 2007-08-28 Lumidigm, Inc. Methods and systems for estimation of personal characteristics from biometric measurements
US20050128485A1 (en) * 2003-12-12 2005-06-16 Singla Madan L. Portable device for total gossypol measurement
EP1706026B1 (en) 2003-12-31 2017-03-01 Sanofi-Aventis Deutschland GmbH Method and apparatus for improving fluidic flow and sample capture
US7822454B1 (en) 2005-01-03 2010-10-26 Pelikan Technologies, Inc. Fluid sampling device with improved analyte detecting member configuration
US20060009727A1 (en) * 2004-04-08 2006-01-12 Chf Solutions Inc. Method and apparatus for an extracorporeal control of blood glucose
EP1751546A2 (en) 2004-05-20 2007-02-14 Albatros Technologies GmbH & Co. KG Printable hydrogel for biosensors
US20110163163A1 (en) * 2004-06-01 2011-07-07 Lumidigm, Inc. Multispectral barcode imaging
US8229185B2 (en) 2004-06-01 2012-07-24 Lumidigm, Inc. Hygienic biometric sensors
US7508965B2 (en) 2004-06-01 2009-03-24 Lumidigm, Inc. System and method for robust fingerprint acquisition
EP1765194A4 (en) 2004-06-03 2010-09-29 Pelikan Technologies Inc Method and apparatus for a fluid sampling device
US9775553B2 (en) 2004-06-03 2017-10-03 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US8787630B2 (en) 2004-08-11 2014-07-22 Lumidigm, Inc. Multispectral barcode imaging
US8652831B2 (en) 2004-12-30 2014-02-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte measurement test time
US20100094114A1 (en) * 2008-10-09 2010-04-15 Mark Ries Robinson Use of multiple calibration solutions with an analyte sensor with use in an automated blood access system
US20090156975A1 (en) * 2007-11-30 2009-06-18 Mark Ries Robinson Robust System and Methods for Blood Access
US20090048576A1 (en) * 2007-08-13 2009-02-19 Mark Ries Robinson Managing Cross-contamination in Blood Samples Withdrawn from a Multilumen Catheter
US20090088615A1 (en) * 2007-10-01 2009-04-02 Mark Ries Robinson Indwelling Fiber Optic Probe for Blood Glucose Measurements
US20090054754A1 (en) * 2007-08-21 2009-02-26 Mcmahon Dave Clinician-controlled semi-automated medication management
US8323194B2 (en) * 2009-12-18 2012-12-04 Inlight Solutions, Inc. Detection of bubbles during hemodynamic monitoring when performing automated measurement of blood constituents
US20100168535A1 (en) * 2006-04-12 2010-07-01 Mark Ries Robinson Methods and apparatuses related to blood analyte measurement system
US7801338B2 (en) 2005-04-27 2010-09-21 Lumidigm, Inc. Multispectral biometric sensors
US20060281187A1 (en) 2005-06-13 2006-12-14 Rosedale Medical, Inc. Analyte detection devices and methods with hematocrit/volume correction and feedback control
US8801631B2 (en) 2005-09-30 2014-08-12 Intuity Medical, Inc. Devices and methods for facilitating fluid transport
EP3461406A1 (en) 2005-09-30 2019-04-03 Intuity Medical, Inc. Multi-site body fluid sampling and analysis cartridge
EP1954190A4 (en) * 2005-11-15 2010-10-13 Luminous Medical Inc Blood analyte determinations
US8182767B2 (en) * 2005-12-27 2012-05-22 Honeywell International Inc. Needle-septum interface for a fluidic analyzer
US7485153B2 (en) * 2005-12-27 2009-02-03 Honeywell International Inc. Fluid free interface for a fluidic analyzer
US8175346B2 (en) 2006-07-19 2012-05-08 Lumidigm, Inc. Whole-hand multispectral biometric imaging
CN101506826A (en) 2006-07-19 2009-08-12 光谱辨识公司 Multibiometric multispectral imager
US7995808B2 (en) 2006-07-19 2011-08-09 Lumidigm, Inc. Contactless multispectral biometric capture
US8355545B2 (en) 2007-04-10 2013-01-15 Lumidigm, Inc. Biometric detection using spatial, temporal, and/or spectral techniques
US7804984B2 (en) 2006-07-31 2010-09-28 Lumidigm, Inc. Spatial-spectral fingerprint spoof detection
US7801339B2 (en) 2006-07-31 2010-09-21 Lumidigm, Inc. Biometrics with spatiospectral spoof detection
EP2120713A2 (en) 2007-03-21 2009-11-25 Lumidigm, Inc. Biometrics based on locally consistent features
EP1985994A1 (en) * 2007-04-27 2008-10-29 Radiometer Medical ApS An optical sensor system
DK2170157T3 (en) * 2007-07-26 2016-12-12 Univ Duke Measuring the quantity of bound and combined nitric oxide in blood
WO2009126900A1 (en) 2008-04-11 2009-10-15 Pelikan Technologies, Inc. Method and apparatus for analyte detecting device
US9833183B2 (en) 2008-05-30 2017-12-05 Intuity Medical, Inc. Body fluid sampling device—sampling site interface
EP3984454A1 (en) 2008-06-06 2022-04-20 Intuity Medical, Inc. Medical diagnostic devices and methods
CA2726067C (en) 2008-06-06 2020-10-20 Intuity Medical, Inc. Detection meter and mode of operation
US9375169B2 (en) 2009-01-30 2016-06-28 Sanofi-Aventis Deutschland Gmbh Cam drive for managing disposable penetrating member actions with a single motor and motor and control system
US9500572B2 (en) 2009-04-30 2016-11-22 Purdue Research Foundation Sample dispenser including an internal standard and methods of use thereof
WO2010138204A1 (en) * 2009-05-29 2010-12-02 Thomson Licensing Method and apparatus for iterative timing recovery
BR112012004177A2 (en) 2009-08-26 2016-03-29 Lumidigm Inc biometric method and system, system, method, object location, object discrimination, and background methods, and multifaceted prism
EP2506768B1 (en) 2009-11-30 2016-07-06 Intuity Medical, Inc. Calibration material delivery devices and methods
US8570149B2 (en) 2010-03-16 2013-10-29 Lumidigm, Inc. Biometric imaging using an optical adaptive interface
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
CA2803797A1 (en) 2010-06-25 2011-12-29 Intuity Medical, Inc. Analyte monitoring methods and systems
US20120129268A1 (en) * 2010-11-19 2012-05-24 Mayer Daniel W Photoluminescent oxygen probe with reduced cross-sensitivity to humidity
EP3750480B1 (en) 2011-08-03 2022-02-02 Intuity Medical, Inc. Body fluid sampling arrangement
US9625465B2 (en) 2012-05-15 2017-04-18 Defined Diagnostics, Llc Clinical diagnostic systems
US9081001B2 (en) 2012-05-15 2015-07-14 Wellstat Diagnostics, Llc Diagnostic systems and instruments
US9213043B2 (en) 2012-05-15 2015-12-15 Wellstat Diagnostics, Llc Clinical diagnostic system including instrument and cartridge
US10008375B2 (en) 2013-01-31 2018-06-26 Purdue Research Foundation Systems and methods for analyzing an extracted sample
BR112015018484A2 (en) 2013-01-31 2017-07-18 Purdue Research Foundation methods of analyzing crude oil
CA2912283A1 (en) 2013-06-21 2014-12-21 Intuity Medical, Inc. Analyte monitoring system with audible feedback
EP3014647B1 (en) 2013-06-25 2018-12-19 Purdue Research Foundation Mass spectrometry analysis of microorganisms in samples
WO2015009970A1 (en) 2013-07-18 2015-01-22 Erythron Llc Spectroscopic measurements with parallel array detector
WO2015010709A1 (en) * 2013-07-22 2015-01-29 Sentec Ag Sensor for detection of gas and method for detection of gas
CN104749157B (en) * 2013-12-27 2019-02-19 同方威视技术股份有限公司 The method and apparatus that safety inspection is carried out to liquid article
US20150338338A1 (en) 2014-02-28 2015-11-26 Erythron, Llc Method and Apparatus for Determining Markers of Health by Analysis of Blood
US9786478B2 (en) 2014-12-05 2017-10-10 Purdue Research Foundation Zero voltage mass spectrometry probes and systems
EP3254297B1 (en) 2015-02-06 2024-04-03 Purdue Research Foundation Probes, systems, and cartridges
WO2016168090A1 (en) 2015-04-14 2016-10-20 Nueon, Inc. Method and apparatus for determining markers of health by analysis of blood
CN106198386A (en) * 2015-05-07 2016-12-07 苏州晋翌生物医学仪器有限公司 Biochemical reaction device and biochemical reaction system
CN108885166B (en) * 2016-02-04 2022-03-08 诺尔生物医药有限公司 Analyte system and method for determining hemoglobin parameters of whole blood
WO2017165403A1 (en) 2016-03-21 2017-09-28 Nueon Inc. Porous mesh spectrometry methods and apparatus
JP6912766B2 (en) * 2016-07-29 2021-08-04 国立大学法人徳島大学 Concentration measuring device
KR101886791B1 (en) 2016-08-17 2018-08-08 연세대학교 산학협력단 Portable blood distinction kit
WO2018085699A1 (en) 2016-11-04 2018-05-11 Nueon Inc. Combination blood lancet and analyzer
DE102021204908A1 (en) * 2021-05-14 2022-11-17 Richard Wolf Gmbh Light applicator system with protective sleeve

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3926521A (en) * 1973-02-21 1975-12-16 Byron E Ginzel Blood collecting and processing means
US4324556A (en) * 1980-03-25 1982-04-13 The United States Of America As Represented By The Secretary Of The Navy Portable COHB analyzer
AT382467B (en) * 1980-12-30 1987-02-25 Max Planck Gesellschaft Optode comprising an indicator and a membrane enclosing the indicator
DK150804B (en) * 1975-09-29 1987-06-22 Jan Evert Lilja SAMPLING SCALE FOR SAMPLING AND OPTICAL ANALYSIS
EP0243116A2 (en) * 1986-04-18 1987-10-28 Minnesota Mining And Manufacturing Company Optical sensor
WO1988001376A1 (en) * 1986-08-14 1988-02-25 Radiometer A/S Method and apparatus for determining the level of an analyte in a sample of whole blood

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3865548A (en) * 1972-06-13 1975-02-11 Einstein Coll Med Analytical apparatus and process
US4180027A (en) * 1977-07-20 1979-12-25 Mack Trucks, Inc. Two-piece oil-cooled piston
IT1158880B (en) * 1978-07-05 1987-02-25 Sclavo Inst Sieroterapeut DEVICE FOR PERFORMING MEASUREMENTS ON FLUIDS DIRECTLY IN THE SAMPLE COLLECTION CONTAINER
US4420254A (en) * 1980-02-19 1983-12-13 Smeaton John R Cuvet and associated apparatus and method for using same
US4657756A (en) * 1980-11-17 1987-04-14 Schering Aktiengesellschaft Microbubble precursors and apparatus for their production and use
US4426451A (en) * 1981-01-28 1984-01-17 Eastman Kodak Company Multi-zoned reaction vessel having pressure-actuatable control means between zones
US4447150A (en) * 1981-02-27 1984-05-08 Bentley Laboratories Apparatus and method for measuring blood oxygen saturation
US4444498A (en) * 1981-02-27 1984-04-24 Bentley Laboratories Apparatus and method for measuring blood oxygen saturation
DE3113797C2 (en) * 1981-04-06 1985-01-31 Hans Uwe Prof. Dr.rer.nat. 7910 Neu-Ulm Wolf Method and arrangement for measuring the acid-base status of blood
EP0072058A1 (en) * 1981-08-10 1983-02-16 Duphar International Research B.V Multiple-compartment syringe
US4509522A (en) * 1981-12-15 1985-04-09 The United States Of America As Represented By The Secretary Of The Navy Infrared optical measurement of blood gas concentrations and fiber optic catheter
US4476870A (en) * 1982-03-30 1984-10-16 The United States Of America As Represented By The Department Of Health And Human Services Fiber optic PO.sbsb.2 probe
AT377095B (en) * 1982-11-23 1985-02-11 List Hans SENSOR ELEMENT FOR DETERMINING THE O2 CONTENT OF A SAMPLE AND METHOD FOR PRODUCING THE SAME
CA1222438A (en) * 1983-05-12 1987-06-02 Steven C. Charlton Unified test means for ion determination
DE3320752A1 (en) * 1983-06-09 1984-12-13 Wolfgang Prof. Dr.Dr. 6500 Mainz Barnikol LUMINESCENT LAYERS FOR USE IN DEVICES FOR DETERMINING THE OXYGEN CONCENTRATION IN GASES AND THE LIKE BY MEASURING THE LUMINESCENT REDUCTION
SE8305704D0 (en) * 1983-10-18 1983-10-18 Leo Ab Cuvette
WO1988000479A1 (en) * 1986-07-11 1988-01-28 Arzneimittel Gmbh Apotheker Vetter & Co. Ravensbur Syringe for medicinal purposes
AT383684B (en) * 1984-09-17 1987-08-10 Avl Verbrennungskraft Messtech ARRANGEMENT FOR FLUORESCENT OPTICAL MEASUREMENT OF SUBSTANCE CONCENTRATIONS IN A SAMPLE
GB8427285D0 (en) * 1984-10-29 1984-12-05 Bellhouse Medical Products Ltd Blood bag
DE3480490D1 (en) * 1984-12-10 1989-12-21 Prutec Ltd Optical test probe and apparatus for optically determining species in solution
DK282085D0 (en) * 1985-06-21 1985-06-21 Radiometer As METHOD AND APPARATUS FOR DETERMINING BLOOD COMPONENTS
US4756884A (en) * 1985-08-05 1988-07-12 Biotrack, Inc. Capillary flow device
US4745279A (en) * 1986-01-02 1988-05-17 American Hospital Supply Corporation Hematocrit measuring apparatus
US4873993A (en) * 1986-07-22 1989-10-17 Personal Diagnostics, Inc. Cuvette
US5029583A (en) * 1986-07-22 1991-07-09 Personal Diagnostics, Inc. Optical analyzer
US4861727A (en) * 1986-09-08 1989-08-29 C. R. Bard, Inc. Luminescent oxygen sensor based on a lanthanide complex
US5120510A (en) * 1986-10-10 1992-06-09 Minnesota Mining And Manufacturing Company Sensor and method for sensing the concentration of a component in a medium
US4737144A (en) * 1987-03-09 1988-04-12 Choksi Pradip V Syringe with selectively exposed and enveloped needle
US4716363A (en) * 1987-05-08 1987-12-29 Hewlett-Packard Company Exponential decay time constant measurement using frequency of offset phase-locked loop: system and method
US4810090A (en) * 1987-08-24 1989-03-07 Cobe Laboratories, Inc. Method and apparatus for monitoring blood components
GB8720470D0 (en) * 1987-08-29 1987-10-07 Emi Plc Thorn Sensor arrangements
US4940945A (en) * 1987-11-02 1990-07-10 Biologix Inc. Interface circuit for use in a portable blood chemistry measuring apparatus
US4929426A (en) * 1987-11-02 1990-05-29 Biologix, Inc. Portable blood chemistry measuring apparatus
DK576187D0 (en) * 1987-11-03 1987-11-03 Radiometer As METHOD OF DETERMINING OXYGEN CONCENTRATION
US5127077A (en) * 1988-07-25 1992-06-30 Abbott Laboratories Fiber-optic physiological probes
AT393565B (en) * 1988-08-09 1991-11-11 Avl Verbrennungskraft Messtech DISPOSABLE MEASURING ELEMENT
US5025798A (en) * 1988-10-31 1991-06-25 Medical Systems Development Corporation Methods and apparatus for directly sensing and measuring blood related parameters
US5046496A (en) * 1989-04-26 1991-09-10 Ppg Industries, Inc. Sensor assembly for measuring analytes in fluids
US5066859A (en) * 1990-05-18 1991-11-19 Karkar Maurice N Hematocrit and oxygen saturation blood analyzer

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3926521A (en) * 1973-02-21 1975-12-16 Byron E Ginzel Blood collecting and processing means
DK150804B (en) * 1975-09-29 1987-06-22 Jan Evert Lilja SAMPLING SCALE FOR SAMPLING AND OPTICAL ANALYSIS
US4324556A (en) * 1980-03-25 1982-04-13 The United States Of America As Represented By The Secretary Of The Navy Portable COHB analyzer
AT382467B (en) * 1980-12-30 1987-02-25 Max Planck Gesellschaft Optode comprising an indicator and a membrane enclosing the indicator
EP0243116A2 (en) * 1986-04-18 1987-10-28 Minnesota Mining And Manufacturing Company Optical sensor
WO1988001376A1 (en) * 1986-08-14 1988-02-25 Radiometer A/S Method and apparatus for determining the level of an analyte in a sample of whole blood

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993006456A1 (en) * 1991-09-19 1993-04-01 Radiometer A/S Method of photometric in vitro determination of the content of an analyte in a sample
US5371020A (en) * 1991-09-19 1994-12-06 Radiometer A/S Method of photometric in vitro determination of the content of an analyte in a sample
EP0539035A2 (en) * 1991-09-30 1993-04-28 Ortho Pharmaceutical Corporation Apparatus and method for measuring a bodily constituent
EP0539035A3 (en) * 1991-09-30 1994-03-16 Ortho Pharma Corp

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