(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property Organization
`International Bureau
`
`(43) International Publication Date
`15 March 2001 (15.03.2001)
`
` URDUAA
`
`(10) International Publication Number
`WO 01/17421 Al
`
`(51) International Patent Classification’:
`GOIN 33/49, 21/55
`
`AGIB 5/00,
`
`(81) Designated States (national): AE, AG, AL, AM, AT, AU,
`AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CR, CU, CZ,
`DE, DK, DM,DZ,EE, ES, FI, GB, GD, GE, GH, GM, HR,
`(21) International Application Number:©PCT/SE00/01740
`HU,ID,IL, IN,IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR,
`LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ,
`NO, NZ, PL, PT, RO, RU,SD, SE,SG, SI, SK, SL, TJ, TM,
`TR, TT, TZ, UA, UG, UZ, VN, YU, ZA, ZW.
`
`(22) International Filing Date:
`7 September 2000 (07.09.2000)
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`English
`
`English
`
`(30) Priority Data:
`9903 182-5
`0001711-1
`
`8 September 1999 (08.09.1999)
`9 May 2000 (09.05.2000)
`
`SE
`SE
`
`(71) Applicant: OPTOQ AB [SE/SE]; Box 20030, S-161 02
`Bromma(SE).
`
`(72) Inventors: LINDBERG,Lars-Géran; Bankekind Haga,
`S-585 93 Linképing (SE). ENLUND, Gunnar; Bergslags-
`gatan 49, S-602 18 Norrkdping (SE). VEGFORS, Mag-
`nus; Hégalidsgatan 15, S-582 45 Linképing (SE).
`
`(74) Agents: LINDBERG,Akeetal.; Bergenstrahle & Lind-
`vall AB, P.O. Box 17704, S-118 93 Stockholm (SE).
`
`(84) Designated States (regional): ARIPO patent (GH, GM,
`KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZW), Eurasian
`patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European
`patent (AT, BE, CH, CY, DE, DK,ES, FI, FR, GB, GR,IE,
`IT, LU, MC, NL, PT, SE), OAPIpatent (BF, BJ, CF, CG,
`Cl, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG).
`
`Published:
`
`With international search report.
`Before the expiration of the time limit for amending the
`claims and to be republished in the event of receipt of
`amendments.
`
`For two-letter codes and other abbreviations,refer to the "Guid-
`ance Notes on Codes and Abbreviations" appearing at the begin-
`ning ofeach regular issue ofthe PCT Gazette.
`
`OAALANAA
`
`1/17421Al
`
`= (54) Titles METHOD AND APPARATUS FOR COMBINED MEASUREMENT OF HEMOGLOBIN AND OXYGEN SATURA-
`TION
`
`(37) Abstract: The present invention relates to a method for accurately detecting SpO», partly by using determination of blood
`characteristics including hemoglobin, in a fluid medium using the reflection of at least one light beam.
`
`1
`
`APPLE 1054
`Apple v. Masimo
`IPR2022-01291
`
`1
`
`APPLE 1054
`Apple v. Masimo
`IPR2022-01291
`
`

`

`WO 01/17421
`
`PCT/SE00/01740
`
`Method and apparatus for combined measurement of hemoglobin
`and oxygen saturation.
`
`The present invention relates to a non-invasive method
`
`for determination of SpO,,
`
`including a first determination of
`
`blood characteristics including hemoglobin (EVF/hematocrit),
`a vessel containing a mixture of liquid and blood cells using
`the orientation effects of the red blood cells. The present
`invention also relates to an apparatus for performing the
`method.
`
`in
`
`Background to the invention
`
`There are different non-invasive methcds known for
`
`measurement of hemoglobin. These methods make use of absorption
`
`of energy at a certain light wavelength, of the red blood cells
`
`(RBCs). Carim et al disclose in US 5755226 a non-invasive
`
`method and apparatus for the direct non-invasive prediction of
`
`hematocrit in mammalian blocd using photopletysmography (PPG)
`
`techniques and data processing. However,
`
`this method only makes
`
`use of the ability of the RBCs to absorb energy. This method is
`
`also quite complicated regarding the formulas which are to be
`
`used when calculating the predicted hematocrit. Thus the method
`
`is time consuming. This method has not taken into account the
`
`red blood cell orientation and distribution in blood vessels.
`
`Further, a method and an apparatus, are disclosed in WO
`
`97/15229 for determining hemoglobin concentration in blood. The
`
`method is used for detecting hemoglobin in the microvascular
`
`system beneath the mucosal membranes on the inside of the lip
`
`of a human subject by introducing a measuring tip into the
`
`mouth of a subject. This means that the measuring tip of the
`
`apparatus must have some kind cf sterile shell before it may be
`
`placed in the mouth. This sterility of the measuring tip means
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`that either the apparatus must be autoclaved before measuring
`
`or that a disposable plastic tip has to be used when performing
`
`the method. This method further uses the reflection of light
`for determining the concentration of hemoglobin.
`.
`
`Photopletmysmography and pulse oximetry has been
`
`thoroughly investigated by two of the present inventors
`
`{"Photopletmysmography, methodological studies and
`
`applications", Lars-Goran Lindberg, Linképing Studies in
`Science and Technology Dissertations, No 262, 1991 and "Pulse
`
`oximetry - methodological considerations", Magnus Vegfors,
`
`Linképing University Medical Dissertations, No 347 1992, both
`
`hereby incorporated by reference thereto).
`
`They found e.g.
`
`that when pulse oximeter was tested on an
`
`artificial bed different flow conditions greatly affected the
`
`accuracy of the pulse oximeter. Different states of the blood,
`
`diluted and haemolysed blood changed the pulse oximeter
`
`accuracy indicating that orientation of red blood celis and the
`
`viscosity of blood as a whole may play important role for the
`
`generation of the two PPG signals utilised in pulse oximetry.
`
`(in Lindberg above)
`
`Further there was mentioned in Vegfots’ paper above about
`
`some previous studies which have indicated that pulse oximeter
`
`accuracy may be dependent on blood haematocrit. For ethical
`
`reasons, it is impossible to study the accuracy of pulse
`
`oximetry on humans at very low haematocrit levels. Therefore,
`
`little human data is available during anaemia. Some
`
`investigations document an increasing negative bias in mildly
`
`anaemic subjects.
`
`The majority of pulse oximeters uses transmitted light to
`
`calculate the oxygen saturation. This limits the probe
`
`application tc for example finger tips,
`
`toes or ear lobes.
`
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`WO 01/17421
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`PCT/SE00/01740
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`There is therefore an increasing interest in reflection pulse
`
`oximetry.
`(Vegfors above) Further examples of pulse oximeters
`are described in the historical review “History of Blood Gas
`
`Analysis. VI. Oximetry”, J. W. Severinghaus and P.B. Astrup,
`
`Journal of Clinical Monitoring, Vol 2, No. 4, October 1986, pp
`
`270-287 (hereby incorporated by reference thereto).
`
`Since haematocrit values outside normal ranges are known
`
`to effect the accuracy of pulse oximetry a combined measurement
`
`of haemoglobin and oxygen saturation it would be desirable with
`
`a method and apparatus which makes it possible to alert for
`
`false pulse oximetry readings and perform on-line corrections.
`
`Accordingly,
`
`there is a need for new methods for
`
`detecting Spo, which takes into account blood characteristics
`
`including Hb, and accordingly also the blood cell orientation
`
`and thus give a more accurate detection value. Further,
`
`methods which do not
`
`involve an extra step of making the
`
`apparatus sterile before measuring or disposable tips are
`
`desirable. The new methods should also be less sensitive to
`
`variations in the blood pressure, e.g.
`
`the pulsative,
`
`(systolic) pressure.
`
`Summary of the invention
`
`The present invention solves the above problems by
`
`increasing the accuracy of pulse oximetry measurements by
`
`reflection and transmittance measurements:
`
`- on central arterial blood vessels better reflecting the
`
`oxygenation than peripheral vascular beds,
`
`- on-line correction for haematocrit values affecting the
`
`accuracy,
`
`- simultaneous results of oxygen saturation and blood
`
`values (such as haematocrit)
`
`improving the quality and safety
`
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`in patient monitoring.
`
`In accordance with a first aspect of the present
`
`invention there is provided a new non-invasive method for
`
`accurate determination of SpO, from a mixture of liquid and
`
`blood cells contained in a light pervious vessel comprising:
`
`a) directing light beams against the mixture;
`
`b) determining at least one blood characteristic other than
`
`Spo, including hemoglobin of thé mixture by analyzing the
`
`intensity of the light reflected from the mixture, or the
`
`intensity of the light reflected from the mixture in
`
`combination with the intensity of the light transmitted through
`
`the mixture; and
`
`c) determining oxygen saturation, SpoO,, of the mixture by
`
`analyzing the intensity of the light transmitted through the
`
`mixture.
`
`In the new method,
`
`(b) and (c) may be performed in the
`
`reverse order or even simultaneously.
`
`In accordance with the invention,
`
`the new method further
`
`comprises establishing whether the result of cc)
`
`is relevant
`
`with respect to the result of b).
`Advantageously,
`(c)
`is performed by pulse-oximetrically
`
`determining oxygen saturation.
`
`With regard to the determination of oxygen saturation,
`
`first,
`
`(a)
`
`is performed by directing at least one light beam
`
`with a wavelength in the red light range against the vessel,
`
`and directing at least one light beam with a wavelength in the
`
`infrared light range against the vessel. Then,
`
`(c)
`
`is performed
`
`by detecting the intensities of the red light and infrared
`
`light transmitted through the mixture, calculating a quotient
`
`of the detected intensities, red/infrared, of the transmitted
`
`light, and determining SpO, by analyzing the quotient.
`
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`By analyzing the quotient of the detected intensities of
`
`transmitted light the advantage is achieved that influences
`
`from pressure and flow,
`
`in particular pulsating flow, of the
`
`liquid mixture is compensated for, whereby the determined Spo,
`
`will be accurate. The quotient is analyzed by comparing it with
`
`previously obtained quotients for known values of Spo,.
`
`With regard to the determination of the blood
`
`characteristic (i.e. at least hemoglobin),
`
`(b)
`
`is performed by:
`
`i) detecting the intensity of the light of the light beams
`
`reflected from the mixture and the intensity of the light of
`
`the light beams transmitted through the mixture;
`
`ii) calculating a quotient of the detected intensity of the
`
`transmitted light and detected intensity of the reflected light
`
`or a quotient of the detected intensity of the reflected light
`
`and detected intensity of the transmitted light; and
`
`iii) analyzing the quotient to determine the blood
`
`characteristic.
`
`By analyzing the quotient of the detected intensities of
`
`transmitted and reflected lights the advantage is achieved that
`
`in particular pulsating
`influences from pressure and flow,
`flow, of the liquid mixture is compensated for, whereby the
`
`determined blood characteristic (hemoglobin) will be accurate.
`
`The quotient is analyzed by comparing it with previously
`
`obtained quotients for known values of the blood characteristic
`
`in question.
`
`Alternatively, first,
`
`(a)
`
`is performed by directing at
`
`least two light beams with different wavelengths against the
`
`vessel,
`
`then,
`
`(b)
`
`is performed by:
`
`1) detecting the intensities of the light of the light beams
`reflected from the vessel;
`
`ii) calculating a quotient of the detected intensities of the
`
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`WO 01/17421
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`.
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`PCT/SE00/01740
`
`reflected lights; and
`
`iii) analyzing the quotient to determine the blood
`
`characteristic.
`
`In accordance with a second aspect of the present
`
`invention there is provided an apparatus for accurate
`
`determination of Spo, from a mixture of liquid and blood cells
`
`contained in a light pervious vessel comprising:
`
`- light sources for directing light beams against the
`
`vessel,
`
`- means for determining a blocd characteristic other than
`
`oxygen saturation, SpO,
`
`including hemoglobin and capable of
`
`analyzing the intensity of the light reflected from the vessel,
`
`or the intensity of the light reflected from the vessel in
`
`combination with the intensity of the light transmitted through
`
`the mixture, and
`
`- means for determining oxygen saturation, SpO,, of the
`
`mixture, preferably pulse-oximetrically, and of analyzing the
`
`intensity of the light transmitted through the mixture.
`
`In accordance with the invention,
`
`the apparatus further
`
`comprises means for establishing whether the determined value
`of Spo, is relevant with respect to the determined value of the
`
`blood characteristic.
`
`The light sources comprise a first light source for
`
`emitting a first light beam with a wavelength in the red light
`
`range against the vessel, and a second light source for
`
`emitting a second light beam with a wavelength in the infrared
`
`light range against the vessel.
`
`The apparatus may further comprise a first detector for
`
`detecting the intensity of the light of the red first light
`
`beam transmitted through the vessel, and a second detector for
`
`detecting the light of the infrared second light beam
`
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`transmitted through the vessel. The oxygen saturation
`
`determining means may comprise a processor adapted to calculate
`
`a quotient of the detected intensities of the transmitted red
`
`and infrared lights and to determine the value of the oxygen
`
`saturation by analyzing the quotient.
`
`The light sources suitably comprise a third light source
`
`for emitting a third light. beam against the vessel, and the
`apparatus may further comprise a third detector for detecting
`
`the intensity of the light of the third light beam reflected
`
`from the vessel and a fourth detector for detecting the
`
`intensity of the light of the third light beam transmitted
`
`through the vessel. The blood characteristic determining means
`
`May comprise a processor adapted to calculate a quotient of the
`
`detected intensities of the reflected and transmitted lights of
`
`the third light beam and to determine the value of the blood
`
`characteristic by analyzing the quotient.
`
`The apparatus may further comprise registration means for
`
`storing the determined blood characteristic and SpO,, and
`
`optionally means for visualization of the determined blood
`
`characteristic and Sp0,.
`In accordance with a third aspect of the present
`
`invention there is provided use of an apparatus according to
`
`the second aspect of the present invention in a dialysis
`
`device.
`
`Detailed description of the invention
`
`The term “light source” is to be understood to encompass
`
`one or more light emitting elements,
`
`such as light diodes.
`
`With the expression “blood characteristics” is meant in
`
`the present application characteristics of blood such as
`
`concentration of blood components, e.g. hemoglobin,
`
`total
`
`8
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`hemoglobin,
`
`red blood cells, white blood cells, platelets,
`
`cholesterol, albumin,
`
`thrombocytes,
`
`lymphocytes, drugs and
`
`other substances, viscosity, blood pressure, blood flow, blood
`
`volume, blood cell illnesses, abnormal blioced cell appearances,
`
`anemia,
`
`leukemia,
`
`lymphoma.
`
`With the expression “hemoglobin” is meant in the present
`
`application oxyhemoglobin,. reduced hemoglobin, carboxy
`hemoglobin, methemoglobin and sulphhemoglobin.
`
`With the expression “red blood cells”, also known as
`
`erythrocytes,
`
`is meant in the present application whole or
`
`partly lysed red blood cells which contain hemoglobin.
`
`With the expression “light pervious vessel” is meant in
`
`the present application a blood vessel
`
`in an animal, a pipe, a
`
`tube or a tubing which is light pervious. The pipe,
`
`tube or
`
`tubing may be manufactured from acrylonitrile butadiene styrene
`
`(ABS), polycarbonate or acrylic glass (polymethylmethacrylate;
`
`PMMA) which gives a non-flexible material or from polyvinyl
`
`chloride (PVC) or silicon rubber, plasticized PVC, e.g. PVC
`
`plasticized with dioctylphtalate, diethylhexyiphtalate or
`
`trioctyltrimellitate, which gives a flexible material.
`PMMA is
`the most preferred non-flexible material. The light pervious
`vessel may further be used when performing liquid transfusions
`
`or blood transfusions. The elasticity of the material may be
`
`varied in a wide range. The animal containing a blood vessel is
`
`preferably a mammal, most preferred a human being.
`
`As used herein, “light” refers generally to
`
`electromagnetic radiation at any wavelength, which includes the
`
`infrared, visible and ultraviolet portions of the spectrum. A
`
`particularly preferred portion of the spectrum is that portion
`
`where there is relative transparency of the tissue, such as in
`
`the visible and near-infrared wavelengths. It is to be
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`understood that for the present invention,
`
`light may be
`
`nonpolarized or polarized light, coherent light or incoherent
`
`light and illumination may be steady pulses of light, amplitude
`
`modulated light or continuos light.
`
`Light sources which may be used in the method and the
`
`apparatus according to the invention are e.g.
`
`light emitting
`
`diodes (LEDs) or laser diodes or combinations therecf such as
`
`VCSEL (vertical cavity surface emitting laser)
`
`. Preferably
`
`less expensive LEDs are used. Today there are also new strong
`
`light emitting diodes which may be used in the method and the
`
`apparatus according to the invention. Flash lamp light sources
`
`are also conceivable for use in the present invention. The
`
`light source may further be capable of emitting monochromatic
`
`Light, i.e. a monochromator. Quartz halogen lamps or tungsten
`
`lamps may also be used as light sources. Optical light fibres,
`
`for guiding the light to and from the measured spot, and or
`
`direct illumination on the measured spot may also be used.
`
`Detectors which may be suitable for use when performing
`
`the method according to the present invention, are
`
`phototransistors, photodicdes, photomultipliers, photocells,
`photodetectors, optical power meters, amplifiers, CCD arrays
`and so on.
`
`In the present application the expression “means for
`
`determining blood characteristics including hemoglobin” refers
`
`to any non-invasive apparatus for determining blood
`
`characteristics including hemoglobin in a liquid comprising
`
`blood cells. Preferred examples of such non-invasive
`
`apparatuses are given below and in the appended claims.
`
`In the present application the expression “means for
`
`determination of Spo,” refers to any apparatus for measuring
`
`oxygen saturation non-invasively in a liquid comprising blood
`
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`10
`
`cells. Preferably pulse-oximetrically measuring apparatuses are
`
`preferred as e.g. are dislosed in Vegfors above and in
`
`Severinghaus et al above, disclosing e.g.
`
`the Minolta pulse
`
`oximeter. The Minolta pulse oximeter uses 650 nm and 805 nm.
`
`The apparatus in Vegfors above is the most preferred, as is
`
`diclosed below.
`
`The mixture of liquid and blood cells in the method of the
`
`present application is preferably flowing, but it may as well
`
`be standing such as is the case for a fluid medium in a blood
`
`bag. The mixture of liquid and blood cells may comprise plasma
`
`or any other liquid as e.g. water or dialysis liquids. The
`
`plasma is preferably in or from a mammal. The liquid may as
`
`well be any other fluid comprising blood cells which may be
`
`obtained during or after the processing of blood.
`
`Further,
`
`the method according to the present application
`
`is also characterized by that it may be performed on a mammal
`
`such as domestic animals or human beings, preferably on a human
`
`being.
`
`The method according to the invention may be performed on
`
`any part of the human body or the body as a whole comprising a
`greater blood vessel, preferably a vein, an arteriole or
`
`artery, most preferred a blood vessel with a diameter >0.1 mm.
`
`The detection is, according to a preferred embodiment of the
`
`present invention, performed on an arm, a toe or a finger. The
`
`detection is most preferably performed on a wrist or on a
`
`finger on the third phalanx.
`
`The present invention, especially the Spo, measuring part
`
`thereof,
`is based upon the principle that individual
`wavelengths of light are absorbed differentlyby various
`components of arterial blood. One application of this principle
`
`is used to measure oxygen saturation of arterial blood.
`
`In
`
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`11
`
`pulse oximetry two wavelengths of light emitted from suitable
`
`light sources are used, one with a wavelength within the red
`
`light range and one within the infrared range. The oximeter
`
`passes light through a monitoring site and measures the
`
`relative absorption of red light preferably at 660 nanometers
`
`(by reduced haemoglobin, Hb) and infrared light preferably at
`
`940 nanometers (by oxyhaemoglobin, HbO,). Because HbO, and Hb
`
`absorb different amounts of. light at each of these two
`
`wavelengths,
`
`the oximeter can compare the ratio of each
`
`absorbance and convert it into an SpO, value. More specific it
`
`may preferably be expressed (AC,.,/DCyeq) / (ACyay/DCo4,) OF ACgep/ACyao
`
`at constant DC levels. Pulse oximetry reduces the effect of
`
`other absorbers by looking only on the pulsative absorbances.
`
`The oximeter considers only the absorbers in the arterial
`
`blood. This is thus in analogy with the measuring global
`
`principle of the present innovation for haemoglobin especially,
`
`and can thus be attained by including preferably 940 nanometers
`
`and preferably 660 nanometers light sources and suitable
`
`detectors.
`
`In one preferred embodiment of the method according to the
`present invention, one or more of the detected intensity of the
`
`light of said light beam(s) reflected from the vessel and the
`
`detected intensity of the light cf said light beam(s)
`transmitted through the vessel,
`is transmitted over a wireless
`connection to a unit for performing step a), e) and/or f),
`
`preferably using a module for wireless communication. The
`
`wireless communication is preferably performed using a
`
`Bluetooth™ standard based communication path.
`
`In the method according to the invention preferably light
`
`beam(s) are directed essentially perpendicular to a measuring
`
`area of the vessel.
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`12
`
`In the method according to the invention preferably the
`
`wavelength of the light in (a), when transmitted light also is
`
`detected,
`
`is from 200 nm to 2000 nm, preferably from 770 nm to
`
`950 nm, most preferred approximately 770, 800, 850, 940 or 950
`nm.
`
`In one preferred embodiment of the method according to the
`
`invention preferably at least two light beams with different
`wavelengths in (a) are directed against the mixture and
`
`selected such that the light absorbance of the red blood cells,
`
`as the first light beam passes theerethrough,
`
`is relatively
`
`insignificant, whereas the wavelength in the second light beam
`
`is selected such that the light absorbance of the red blood
`
`cells, as the second light beam passes therethrough,
`
`is
`
`relatively significant.
`
`In one preferred embodiment of the method according to the
`
`invention preferably at least two light beams with different
`
`wavelengths in (a) are directed against the vessel, preferably
`essentially in parallel with each other, wherein one with a
`wavelength of from 770 to 950 nm and the other with a
`
`wavelength of from 480 to 590 nm.
`In one preferred embodiment of the method according to the
`invention,
`in (a)
`light is emitted from at least four light
`
`sources, preferably six light sources, wherein the light
`
`sources being adapted to appear on either side of the
`
`detector(s), preferably the light sources are arranged in
`
`groups of two, most preferred in groups of three when six light
`
`sources are present, most preferred the light sources form an
`
`“y” with one detector in the centre. Preferably the “H” above is
`
`tilted approximately 30° during the measurement on preferably a
`
`wrist when looking from the direction of the arm or the blood
`
`vessel. The measurement is further preferably performed on the
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`inside of the wrist.
`
`In one preferred embodiment of the method according to the
`
`invention,
`
`in (a)
`
`light is emitted from two light sources,
`
`which are positioned and thus appearing on two different
`
`opposite sides of a vessel containing the mixture, and
`
`detection of reflected light from and transmitted light through
`
`the vessel is performed by. at least two detectors, preferably
`by only two detectors.
`|
`In one preferred embodiment of the methed according to the
`
`invention (b) comprises the following steps:
`
`I)
`
`sweeping a window over a curve with detected values from
`
`transmission and/or reflection, wherein the size of said window
`
`preferably is approximately 60 % of the period time, divided
`
`equally to the right and to the left;
`
`II)
`
`if no value within said window is higher than the middle
`
`value, designating the value a maximum point whereupon moving
`
`the window by leap half of the window length, or if a value
`
`exceeds the middle value moving the window only one step;
`
`III) designating the minimum points in the same manner as in
`
`II) but with regards to minimum values instead of maximum
`values;
`°
`IV) obtaining the height of the AC-signal by subtracting from
`
`a value on a connection line involving two maximum points,
`
`the
`
`vertically laying value of an in between laying minimum point;
`
`V) xvepeating step IV) at least 8 times, and summarizing the
`
`values from IV) and dividing the sum with the number of
`
`observations,
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`thus obtaining a median AC-value; and
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`VI) optionally obtaining the DC-signal by adding the total
`
`height of the minimum point in IV)
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`to the median AC-signal of
`
`step V);
`
`whereby preferably using a computer program for obtaining said
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`AC-signal and optionally said DC-signal.
`
`In one preferred embodiment of the method according to the
`
`present invention the wavelength of the red light is
`
`approximately 660 nm and the wavelength of the infrared light
`
`is approximately 940 nm.
`
`In the method according to the invention, preferably the
`
`determined SpO, and determined blood characteristics including
`hemoglobin are presented simultaneously.
`
`In the method according to the invention, preferably the
`
`determined SpO, is corrected by using the determined blood
`
`characteristics including hemoglobin.
`
`The method according to the present invention may,
`
`according to a preferred embodiment, be used for determination
`
`of blood characteristics including hemoglobin in extracorporeal
`
`equipments including e.g. dialysis apparatuses (dialysers),
`
`cell savers, dialysis monitors, or on a blood bag device (which
`
`includes assemblies), or on a slaughter house device, or on a
`
`blood fractionation device. The light pervious vessel,
`
`preferably a tube or pipe, may in this embodiment of the
`
`present invention have a diameter >0.1 mm.
`In dialysis
`apparatuses it may be desirable to see how much hemogiobin and
`
`the SpO, value which is present in a fluid which is subjected
`
`to any form of dialysis, preferably hemodialysis. During
`
`dialysis it may further be desirable to measure the hemoglobin
`
`concentration in order to follow changes in blood volume of the
`
`patient and Spo, in said patient. Regarding blood bag
`
`constructions and blood bag assemblies,
`
`the method according to
`
`the invention may be applied to tubings, bags, filters or any
`
`other component that may be used in association with blood bags
`
`which may contain whole blood or buffy coat i.e. concentrate of
`
`white blood cells (leukocytes). The method may alsc be used
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`during blood transfusions on tubings, or during blood donations
`
`as well.
`
`In slaughter houses,
`
`the method according to the
`
`present application may be useful when recovering blood from
`
`slaughter animals and when further processing that blood to
`
`give whole blood for use directly in food or fractionate it to
`
`obtain the blocd components albumin,
`
`immunoglobulins and so on.
`
`The method according to the present application may also be
`used when counting blood cells i.e. a process when you count
`
`red and white blood cells. This may be done in an apparatus
`such as a blood cell counter e.g. a Coulter counter
`
`manufactured by Coulter Diagnostics of Miami Florida. The
`
`method according to the invention may also be used in
`
`association with blood analysing, blood typing and other blood
`
`gas analyses,
`
`in addition to SpO,. The method according to the
`
`invention may also be used when fractionating human blood in a
`
`blood fractionating unit. It may be desirable to use the method
`
`according to the present application when plasma is obtained
`
`from donors. The method may also be useful when obtaining buffy
`
`coats from a donor or when these buffy coats are further
`
`processed for producing e.g. cytokines such as interferon
`alpha. The method may be useful to determine how the lysis of
`the RBC:s are performing during the purification of white blood
`
`cells which subsequently after one or more steps involving RBC
`
`lysis with e.g. ammonium chloride, are exposed to virus e.g.
`
`Sendai virus during incubation in a suitable medium e.g. Eagles
`
`Minimal Essential Medium, EMEM.
`
`The method, according to the present application,
`
`is
`
`preferably performed on a blood vessel,
`
`tube or pipe.
`
`According to a preferred embodiment of the present
`
`invention the light beams are preferably directed essentially
`
`perpendicular to a measuring area of a vessel containing the
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`mixture.
`
`According to a preferred embodiment of the present
`
`invention, at least two light beams are directed against the
`
`vessel from two light sources and detection of the intensity of
`
`the reflected light from the vessel is performed by at least
`
`one detector, preferably by only one detector.
`
`According to yet another preferred embodiment of the
`method according to the present invention,
`in step a) at least
`
`two light beams, preferably with two different wavelengths, are
`
`directed against the vessel,
`
`from two light sources,
`
`(which may
`
`be incorporated in the same shell, e.g. a chip), which are
`
`positioned and thus appearing on one common side of the
`
`measuring object. These light sources may when used together in
`
`a chip be lightened alternately. One of the light beams may
`
`have a wavelength of from 770 nm to 950 nm, preferably 770,
`
`800, 850, 940 or 950 nm, and the other may have a wavelength of
`
`from 480 nm to 590 nm, preferably 500 nm.
`
`An apparatus according to one preferred embodiment of the
`
`present invention may comprise at least four light sources and
`at least two detectors for reflected light, wherein two light
`sources have different wavelengths for directing two light
`
`beams appearing on the same side of the vessel, wherein
`
`preferably one light source is having a wavelength of from 770
`
`to 950 nm and the cther a wavelength of from 480 to 590 nm.
`
`In an apparatus according to one preferred embodiment of
`
`the present invention at least two components of the apparatus
`
`May communicate with each other over a wireless connection,
`
`preferably over a module for wireless communication. The module
`
`for wireless communication may comprise at least one
`
`transmitter and one receiver.
`
`In an apparatus according to a preferred embodiment cf the
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`present invention there may be one module for wireless
`
`communication between at least three components, i.e.
`
`light
`
`sources,
`
`light detectors, and
`
`the processor and/or one module
`
`for wireless communication between the processor and the
`
`registration means.
`
`In an apparatus according to a preferred embodiment of the
`
`present invention the wireless communication may be performed
`using a Bluetooth™ standard based communication path.
`
`In an apparatus according to a preferred embodiment of the
`
`present invention the light sources may be positioned.
`
`essentially perpendicular to a measuring area of the vessel.
`
`In an apparatus according to a preferred embodiment of the
`
`present invention the wavelength of at least one of the light
`
`is from 200 nm to 2000 nm, preferably from 770 nm to 950 nm,
`
`most preferred approximately 770, 800, 850, 940 or 950 nm.
`
`An apparatus according to a preferred embodiment of the
`
`present invention may have two light sources for directing two
`
`light beams with different wavelengths on the same side of the
`
`vessel, whereby one of the light beams having a wavelength of
`
`from 770 nm to 950 nm, preferably 770, 800, 850, 940 or $50 nm,
`and the other light beam having a wavelength of from 480 to 590
`
`nm, preferably 500 nm.
`
`An apparatus according to a preferred embodiment of the
`
`present invention may comprise at least four light sources on
`
`one common side, preferably at least six light sources, wherein
`
`the light sources being adapted to appear on either side of the
`
`detector(s), preferably the light sources are arranged in
`
`groups of two , preferably groups of three, wherein the light
`
`sources preferably form an “H” with one detector in the centre.
`
`An apparatus according to a preferred embodiment