EP0805981A1 - Detecteur d'hemolyse jetable - Google Patents

Detecteur d'hemolyse jetable

Info

Publication number
EP0805981A1
EP0805981A1 EP96902156A EP96902156A EP0805981A1 EP 0805981 A1 EP0805981 A1 EP 0805981A1 EP 96902156 A EP96902156 A EP 96902156A EP 96902156 A EP96902156 A EP 96902156A EP 0805981 A1 EP0805981 A1 EP 0805981A1
Authority
EP
European Patent Office
Prior art keywords
volume
sample
sealed chamber
hemolysis
chamber
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP96902156A
Other languages
German (de)
English (en)
Inventor
Kyu H. Lee
John A. Taylor
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Therakos Inc
Original Assignee
Therakos Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Therakos Inc filed Critical Therakos Inc
Publication of EP0805981A1 publication Critical patent/EP0805981A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G01N33/491—Blood by separating the blood components

Definitions

  • the present invention relates to systems and methods for detecting hemolysis in a patient's blood, and in particular, to disposable systems that may be used to detect hemolysis in non-laboratory environments. Even more particularly, the present invention relates to systems and methods that clinicians may use in a patient's room for detecting hemolysis.
  • hemolysis is typically detected during extracorporeal therapies by first taking a sample of a patient's blood to a laboratory where the sample is placed in a rotating centrifuge for separating the red blood cells in the sample from the plasma, and then comparing the colors of the plasma before and after or during treatment.
  • Hemolysis testing systems which require the use of a centrifuge and a laboratory are unsatisfactory because it is possible that hemolysis may occur to a significant degree during the time that the tost itself is being performed.
  • another known method for separating out the plasma portion of a blood sample involves the use of a icroporous membrane device which allows only non-cellular elements of a blood sample to permeate a membrane.
  • microporous membrane devices typically require a relatively high shear rate of the blood sample at the surface of the membrane to prevent the cellular elements of the blood sample from clogging or plugging the membrane pores.
  • Membrane plasma separators therefore require complicated flow systems to maintain a shear rate at the membrane surface that is both high enough to promote a good plasma flux through the membrane without any clogging of the membrane pores and also low enough to prevent damage to blood cells that are separated from the plasma by the membrane.
  • such systems are complex, expensive, and typically require a large sample volume in order to detect hemolysis.
  • membrane plasma separators require high shear rates at the membrane surface to keep blood cells away from the membrane surface and to prevent such blood cells from clogging the membrane pores.
  • Fig. 1 is a perspective view of a hemolysis detector according to a preferred embodiment of the present invention.
  • Fig. 2 is a perspective view showing the preferred hemolysis detector of Fig. 1 in its inverted position.
  • Fig. 3 is a sectional view showing the preferred hemolysis detector of Fig. 2.
  • Fig. 4 is a perspective view of a system for collecting and channeling the plasma portion of a blood sample in accordance with a preferred embodiment of the present invention.
  • Fig. 5 is a top view of the system for collecting and channeling the plasma portion of a blood sample shown in Fig. 4.
  • Fig. 6 is a sectional view of the system for collecting and channeling the plasma portion of a blood sample shown in Fig. 5.
  • Fig. 7 is a diagram illustrating a preferred method for using the hemolysis detector of Fig. 1 to detect hemolysis in a patient's blood sample.
  • Fig. 8 is a perspective view of a hemolysis detector according to a further preferred embodiment of the present invention.
  • Fig. 9 is a perspective view showing the preferred hemolysis detector of Fig. 8 in its inverted position.
  • Fig. 10 is a sectional view showing the preferred hemolysis detector of Fig. 8.
  • Fig. 11 is a diagram illustrating a preferred method for using the hemolysis detector of Fig. 8 to detect hemolysis in a patient's blood sample.
  • Fig. 12 is a perspective view of a hemolysis detector according to a still further preferred embodiment of the present invention.
  • Fig. 13 is a perspective view showing the preferred hemolysis detector of Fig. 12 in its inverted position.
  • Fig. 14 is a sectional view showing the preferred hemolysis detector of Fig. 12.
  • Fig. 15 is a diagram illustrating a preferred method for using the hemolysis detector of Fig. 12 to detect hemolysis in a patient's blood sample.
  • Fig. 16 is a top view showing a hemolysis detector according to a still further preferred embodiment of the present invention.
  • Fig. 17 is a sectional view of the hemolysis detector of Fig. 16.
  • Fig. 18 is sectional view showing a hemolysis detector according to a still further preferred embodiment of the present invention.
  • Fig. 19 is sectional view showing a hemolysis detector according to yet a still further preferred embodiment of the present invention.
  • Fig. 20 is sectional view showing a hemolysis detector according to yet a still further preferred embodiment of the present invention.
  • the present invention is directed to a method and apparatus for detecting hemolysis from a sample of a patient's blood.
  • a sealed chamber having a fixed volume is provided for receiving the sample of blood.
  • the sealed chamber has an internal pressure resulting from a presence of a fixed quantity of air inside the chamber.
  • a volume of fluid that includes the sample of blood is received into the sealed chamber. While the sample is being received into the sealed chamber, the internal pressure of the sealed chamber is raised to an increased internal pressure by retaining the fixed quantity of air inside the sealed chamber as the fluid is received into the chamber.
  • the increased internal pressure causes the plasma portion of the blood sample in the chamber to permeate a membrane that forms at least a portion of one side of the chamber.
  • a test volume of the plasma portion of the sample is received by a hemolysis detection means after the test volume of the plasma portion has permeated the membrane, and a hemolysis condition is detected in accordance with a hue associated with the test volume received into the hemolysis detection means.
  • a hemolysis detector for detecting hemolysis from a sample of blood includes a sealable chamber having means for receiving a volume of fluid that includes a sample of blood into the chamber. Means for transforming the sealable chamber into a sealed chamber having an internal pressure resulting from a presence of a fixed quantity of air inside the sealed chamber are also provided.
  • the means for receiving the volume of fluid into the chamber includes means for raising the internal pressure to an increased internal pressure as the fluid is received into the chamber by retaining the fixed quantity of air in the sealed chamber as the volume of fluid is received into the chamber.
  • the means for transforming the sealable chamber into a sealed chamber is formed of a membrane which is permeable to a plasma portion of the sample in the sealed chamber when the internal pressure in the chamber is equivalent to the increased internal pressure.
  • Hemolysis detection means positioned outside of the chamber for receiving a test volume of the plasma portion of the sample after it has permeated the membrane is also provided.
  • the hemolysis detection means detects a hemolysis condition in accordance with a hue associated with the test volume of the plasma portion of the sample.
  • a system for detecting a blood constituent of interest from a sample of whole blood comprises a membrane for separating a plasma portion of the sample from a cellular portion of the sample.
  • the membrane has a first side for receiving the sample of whole blood and a second side for passing only a plasma portion of the whole blood sample.
  • a blood barrier is coupled to and positioned against the first side of the membrane such that the blood barrier defines a perimeter enclosing the first side of said membrane.
  • An indicator paper that is responsive to the blood constituent of interest is also provided. The indicator paper is coupled to the membrane and positioned against the second side of the membrane.
  • a system for detecting a blood constituent of interest from a sample of whole blood comprises a membrane for separating a plasma portion of the sample from a cellular portion of the sample of blood.
  • the membrane has a first side for receiving the sample of whole blood and a second side for passing only the plasma portion of the sample of whole blood.
  • a blood barrier is coupled to and positioned against the first side of the membrane such that the blood barrier defines a perimeter enclosing the first side of the membrane.
  • An indicator paper is coupled to the membrane by a plasma channelling means that is positioned against the second side of the membrane. The indicator paper is responsive to the blood constituent of interest.
  • the sample of whole blood is placed inside the perimeter and in contact witn the first side of the membrane.
  • the plasma portion of the sample is collected as it permeates the membrane and then channelled with the channelling means to the indicator paper.
  • a determination of whether the constituent of interest is present in the whole blood sample is then made by observing the hue of the indicator paper.
  • Hemolysis detector 100 is formed of a sealable chamber 110 having a sample injection port 120 for receiving a sample of blood into the sealed chamber.
  • Sealable chamber 110 is preferably formed of a clear rigid plastic and has a fixed internal volume. Suitable plastics for forming sealable chamber 110 include acrylic, PVC, polycarbonate or polysulfone.
  • Sample injection port 120 is preferably formed of latex rubber or other elastic material.
  • Sealable chamber 110 is mounted on a chamber base 130 which is also preferably formed of a clear rigid plastic.
  • a microporous membrane disk 140 (not shown in Fig. 1, but shown in Fig.
  • Microporous membrane disk 140 preferably has a pore size in the range of 0.2 to 1.2 microns, and still more preferably between 0.45 - 0.80 microns. In the preferred embodiment, membrane disk 140 is only permeable to the plasma portion of a whole blood sample and non-permeable to the cellular portion of the sample.
  • a channelling means 150 is positioned immediately below microporous membrane disk 140. The channelling means 150 collects the plasma portion of a whole blood sample as that plasma portion permeates through the membrane disk 140 and then channels that plasma portion to a clear capillary tube 160.
  • Hemolysis detector 100 is preferably assembled by positioning the channelling means 150 within the chamber base 130, and then ultrasonically welding sealable chamber 110 to chamber base 130 with membrane disk 140 located in-between.
  • Fig. 7 there is shown a diagram illustrating a preferred method for using hemolysis detector 100 to detect hemolysis in a patient's blood sample.
  • the process begins in step 1 by injecting a wetting solution such as saline into sealable chamber 110.
  • the wetting solution is preferably injected into sealable chamber 110 with a syringe that has been inserted through the sample injection port 120.
  • hemolysis detector 100 is inverted thereby causing the wetting solution injected during step 1 to wet the membrane disk 140 positioned at the bottom of sealable chamber 110.
  • This wetting step causes the membrane disk 140 (which was previously dry and therefore permeable to air) to become impervious to air, thereby transforming sealable chamber 110 into a sealed chamber having a fixed volume of air inside.
  • a sample of a patient's whole blood is injected into sealed chamber 110 through sample injection port 120. Since sample injection port 120 is made of latex or rubber, no air escapes from sealed chamber 110 during injection of the whole blood sample into the chamber.
  • the volume of the whole blood sample injected into sealed chamber 110 in step 3 preferably corresponds to 1-10% of the fixed internal volume of sealed chamber 110. Since fluid is added to sealed chamber 110 in step 3 but no air is allowed to escape from the chamber, the internal pressure in sealable chamber rises by approximately 8-80mm Hg as a result of the injection of the whole blood sample into the sealed chamber during this step.
  • the volume of whole blood injected during step 3 is measured precisely such that the internal pressure in sealable chamber 110 is raised by 28-30 mm Hg when the whole blood sample is injected into the sealed chamber 110.
  • the change in pressure that results from the injection of a whole blood sample into the sealed chamber 110 can be easily determined by solving equation (1) below for the quantity P 2 :
  • V represents the volume of air in sealed chamber 110 prior to the injection of the whole blood sample into the chamber
  • P represents the pressure of the air in sealed chamber 110 prior to the injection of the whole blood sample into the chamber (this will typically be the ambient air pressure)
  • V 2 represents V, minus the volume of the whole blood sample injected into sealed chamber 110 during step 3
  • P 2 represents the air pressure within sealed chamber 110 after the whole blood sample has been injected into the chamber.
  • the membrane disk 140 is itself used as the means for transforming sealable chamber 110 into a sealed chamber because the membrane disk 110 (which originally was in a dry state and pervious to air) becomes impervious to air when it is wetted.
  • other means such as a sealable valve or opening (not shown) positioned between the interior of chamber 110 and the cutside may be used to transform chamber 110 into a sealed state.
  • hemolysis detector 100 is shaken to mix the whole blood sample injected into the sealed chamber 110 during step 3 with any wetting solution remaining in the sealed chamber 110 from step 1.
  • step 5 hemolysis detector 100 is inverted, and the plasma portion of the whole blood sample previously injected into the chamber then permeates through membrane disk 140.
  • the increased internal pressure generated by the injection of the whole blood sample into sealed chamber 110 in step 3 functions during step 5 as an urging force to push the plasma portion of the whole blood sample through the membrane disk 140.
  • the increased internal pressure generated by the injection of the whole blood sample into sealed chamber 110 should be great enough to urge the plasma portion of the blood sample through the membrane disk 140, but not so great as to cause damage to the blood sample.
  • the surface area of membrane disk 140 may be on the order of 3.14 square centimeters and, in step 5 of the process of Fig. 7, 0.1 to 0.15 ml of plasma will permeate membrane disk 140.
  • the ratio of plasma volume permeating the membrane to the membrane surface area is 0.318 ml/sq. cm. of membrane surface area.
  • the ratio of plasma volume to membrane surface area may range from 0.1 to 1.0 ml/sq. cm. of membrane surface area.
  • the sample injection port 120 functions to raise t.-.e internal pressure inside chamber 110 as the sample is injected into the sealed chamber by retaining a fixed quantity of air inside the chamber as the sample is received into the chamber
  • other means such as a manual pressure pump (not shown) may also be used to increase the internal pressure inside the sealed chamber 110.
  • step 5 As the plasma portion of the whole blood sample permeates membrane disk 140 in step 5, this plasma portion is collected by channelling means 150 and then channeled into clear capillary tube 160.
  • hemolysis detector 100 is inverted again and the hue or tint of the plasma in capillary tube 160 is observed either with the naked eye or with a column magnifier (not shown) . If the hue of the plasma is amber, this indicates that the whole blood sample was normal. Alternatively, if the hue of the plasma is pink, this indicates that hemolysis has occurred.
  • the clear capillary tube 160 may be used alone to detect whether hemolysis has occurred in the sample simply by observing the hue or tint of plasma in the tube, in alternate embodiments an indicator paper such as guaiac paper (described below in conjunction with detector 400) may be used to detect hemolysis from the plasma after it has permeated through the membrane disk 140.
  • an indicator paper such as guaiac paper (described below in conjunction with detector 400) may be used to detect hemolysis from the plasma after it has permeated through the membrane disk 140.
  • Channelling means 150 is formed of a plurality of interconnected v-shaped channels 152. Each adjacent pair of channels 152 is joined at a ridge 154. Ridges 154 are positioned against membrane disk 140 when hemolysis detector 100 is in its assembled state.
  • a collection channel 156 is coupled to each of the channels 152 and to clear capillary tube 160.
  • channels 152 are v-shaped, in alternate embodiments such channels may be u-shaped. In addition, in alternate embodiments, channels 152 may be coupled to capillary tube 160 through multiple collection channels. Finally, in a still further alternate embodiment (not shown) , a channelling means 150 may be formed of a bowl- shaped container with capillary tube 160 coupled to the lower-most portion of the bowl, such that the bowl catches plasma as it permeates through membrane disk 140 and then channels that plasma by gravity to the capillary tube 160.
  • hemolysis detector 200 is substantially equivalent to hemolysis detector 100, except, as explained more fully below, hemolysis detector 200 is shaped slightly differently and has its sample injection port 220 located on the lengthwise portion of sealable chamber 210.
  • hemolysis detector 200 is formed of a sealable chamber 210 having a sample injection port 220 for receiving a sample of blood into the sealed chamber.
  • sealable chamber 220 is preferably formed of a clear rigid plastic and has a fixed internal volume.
  • Sealable chamber 210 is mounted to a chamber base 230 which is also preferably formed of a clear rigid plastic.
  • a microporous membrane disk 240 (not shown in Fig. 8, but shown in Fig. 10) is provided at and forms one end of sealable chamber 210. Microporous membrane disk 240 is substantially equivalent to membrane disk 140.
  • a channelling means 250 is positioned immediately adjacent to microporous membrane disk 240. The channelling means 250 collects the plasma portion of a whole blood sample as that plasma portion permeates through the membrane disk 240 and then channels that plasma portion to a clear capillary tube 260.
  • FIG. 11 there is shown a diagram illustrating a preferred method for using hemolysis detector 200 to detect hemolysis in a patient's blood sample.
  • hemolysis detector 200 is used in substantially the same manner as hemolysis detector 100, except that in hemolysis detector 200 the injection of the saline solution and whole blood sample in steps 1 and 3 is accomplished using a sample injection port positioned along the lengthwise portion of chamber 210.
  • Hemolysis detector 300 is formed of a sealable chamber 310 having a sample injection port 320 for receiving a sample of blood into the sealed chamber.
  • Sealable chamber 310 is preferably formed of a clear rigid plastic and has a fixed internal volume.
  • a capillary tube cover 330 is secured to sealable chamber 310.
  • Capillary tube cover 330 is also preferably formed of a clear rigid plastic.
  • a microporous membrane disk 340 (not shown in Figs. 12-13, but shown in Fig. 14) is provided at and forms a boundary defining one wall of sealable chamber 310.
  • hemolysis detector 300 is formed of a sealable chamber 310 that is essentially L-shaped.
  • the internal portion of hemolysis detector 300 occupied by sealable chamber 310 is indicated in Fig. 14 by parallel line shading.
  • the microporous membrane disk 340 in hemolysis detector 300 preferably has a pore size in the range of 0.2 to 1.2 microns, and still more preferably between 0.45 - 0.80 microns, and is only permeable to the plasma portion of a whole blood sample and non-permeable to the cellular portion of the sample.
  • a channelling means 350 is positioned immediately adjacent to microporous membrane disk 340.
  • the channelling means 350 collects the plasma portion of a whole blood sample as that plasma portion permeates through the membrane disk 340 and then channels that plasma portion to a clear capillary tube 360.
  • Hemolysis detector 300 is preferably assembled by positioning the channelling means 350 within the capillary tube cover 330, and then ultrasonically welding sealable chamber 310 to the cover 330 with membrane disk 340 located in-between.
  • Fig. 15 there is shown a diagram illustrating a preferred method for using hemolysis detector 300 to detect hemolysis in a patient's blood sample.
  • the process begins in step 1 by injecting a wetting solution such as saline into sealable chamber 310 through the sample injection port 320.
  • hemolysis detector 300 is tipped sideways and agitated, thereby causing the wetting solution injected during step 1 to wet the membrane disk 340.
  • This wetting step causes the membrane disk 340 (which was previously dry and therefore permeable to air) to become impervious to air, thereby transforming sealable chamber 310 into a sealed chamber having a fixed volume of air inside.
  • step 3 a sample of a patient's whole blood is injected into sealed chamber 310 through sample injection port 320. Since sample injection port 320 is made of latex or rubber, no air escapes from sealed chamber 310 during injection of the whole blood sample into the chamber.
  • the volume of the whole blood sample injected into sealed chamber 310 in step 3 preferably corresponds to 1-10% of the fixed internal volume of sealed chamber 310. As discussed above in connection with hemolysis detector 100, the addition of this fluid into the sealed chamber causes its internal pressure to rise by approximately 8-80mm Hg, and preferably by 28-30 mm Hg.
  • step 4 of the process hemolysis detector 300 is shaken to mix the whole blood sample injected into the sealed chamber 310 during step 3 with any wetting solution remaining in the sealed chamber 310 from step 1.
  • step 5 hemolysis detector 300 is inverted, and the plasma portion of the whole blood sample previously injected into the chamber tnen permeates through membrane disk 340.
  • the increased internal pressure generated by the injection of the whole blood sample into sealed chamber 310 in step 3 and the downward pressure created by the weight of the whcla blocd sample itself together function during step 5 as an urging force to push the plasma portion of the whole blood sample in an upward direction through the membrane disk 340.
  • this plasma portion of the whole blood sample permeates membrane disk 340 in step 5
  • this plasma portion is collected by channelling means 350 and then channeled in an upward direction into clear capillary tube 360.
  • the hue or tint of the plasma in capillary tube 360 is observed either with the naked eye or with a column magnifier (not shown) . If the hue of the plasma is amber, this indicates that the whole blood sample was normal. Alternatively, if the hue of the plasma is pink, this indicates that hemolysis has occurred.
  • Hemolysis detector 400 is formed of a microporous membrane disk 410 for separating the plasma portion of a sample of whole blood from the cellular portion of the whole blood sample.
  • Membrane disk 410 has a first side 420 for receiving the sample of whole blood to be separated.
  • the whole blood sample is preferably received onto membrane disk 410 by placing one or more drops of the whole blood sample onto the first side 420 of membrane disk 410.
  • Microporous membrane disk 410 preferably has a pore size in the range of 0.2 to 1.2 microns, and still more preferably between 0.45 - 0.80 microns. Since membrane disk 410 is only permeable to the plasma portion of a whole blood sample and non-permeable to the cellular portion of the sample, cnly plasma from the whole blood sample placed on first side 420 will pass through to the second side 430 of membrane disk 410.
  • Membrane disk 410 is preferably formed from of a hydrophilic membrane such as Thermopor 800, Verapor 800, or Supor 800 made by Gelman Science, Inc.
  • membrane disk 410 is 5 - 10 mm in diameter, although disks having larger or smaller diameters could also be used. It will also be understood by those skilled in the art that membranes formed in shapes other than disks could also be used in place of membrane disk 410.
  • a blood barrier 440 is coupled to and positioned against the first side 420 of membrane disk 410.
  • Blood barrier 440 is preferably circular in shape and defines a perimeter 450 enclosing the first side 420 of membrane disk 410.
  • membrane disk 410 and blood barrier 440 are glued together, although these elements could be secured to each other using other means of attachment.
  • Blood barrier 440 is preferably formed of a molded plastic material.
  • hemolysis detector 400 is further formed of an indicator paper disk 460 which is secured inside a plastic casing 470 by glue 480 or by other attachment means.
  • Indicator paper disk 460 is preferably positioned directly adjacent to and in contact with the second side 430 of membrane disk 410.
  • Indicator paper disk 460 is also preferably coupled to membrane disk 410 in a detachable manner so that indicator disk 460 and membrane disk 410 can be easily separated.
  • Indicator paper disk 460 is preferably for ⁇ r.ad of a porous paper impregnated with guaiac resin such as Hemoccult paper manufactured by S ithKline Diagnostics, Inc. Such paper displays a blue color in the presence of hemoglobin when treated with a hydrogen peroxide solution.
  • a suitable hydrogen peroxide solution for use in conjunction with this aspect of the present invention is the Hemoccult Developer manufactured by SmithKline Diagnostics, Inc.
  • Indicator paper disk 460 preferably has a larger diameter than membrane disk 410 and, in the embodiment shown, is approximately 20mm in diameter. Since in the preferred embodiment indicator paper disk 460 is larger than membrane disk 410, a portion of indicator paper disk 460 will lie outside of perimeter 450. It will, however, be understood by those skilled in the art that indicator paper formed in shapes other than disks could also be used in place of disk 460.
  • membrane disk 410 To test for the presence of free hemoglobin in a sample of whole blood using hemolysis detector 400, one or more drops of a whole blood sample is placed within perimeter 450 on the first side 420 of membrane disk 410.
  • membrane disk 410 is formed of a hydrophobic or slightly hydrophilic paper, membrane disk 410 should be pre-wetted with a wetting solution such as an aqueous solution of 5-20% isopropyl alcohol or ethyl alcohol prior to dropping the whole blood sample onto the membrane disk 410.
  • a wetting solution such as an aqueous solution of 5-20% isopropyl alcohol or ethyl alcohol
  • Other organic solvents can also be used as a wetting agent, so long as these solvents do not leave a residue in membrane disk 410 that could interfere with the blood test.
  • the purpose of this pre-wetting step is to hydrophilize the membrane disk.
  • the pre-wetting step can be accomplished by simply dropping one or more drops of the wetting solution onto the membrane disk 410. After one or more drops of a whole blood sample is placed within perimeter 450 on the first side 420 of membrane disk 410, the plasma portion of the whole blood sample will wet the membrane disk 410 as well as the indicator paper disk 460 lying beneath the membrane disk 410. If the wetting of the indicator paper disk 460 propagates beyond perimeter 450, a drop of developer solution is applied to the wetted portion of the indicator paper disk 460 lying outside of perimeter 450. If blue color appears in the wetted area after approximately one minute, this is an indication of free hemoglobin in the plasma and hemolysis is therefore detected as being present.
  • membrane disk 410 should be removed from its position above the indicator paper disk 460 and a drop of developer solution should then be applied to the wetted portion of the indicator paper disk 460 previously lying below membrane disk 410. Again, if blue color appears in the wetted area after approximately one minute, this is an indication of free hemoglobin in the plasma and hemolysis is therefore detected as being present.
  • detector 400 Although in the embodiment of detector 400 described immediately above, the blood constituent of interest is free hemoglobin and an indicator paper impregnated with guaiac resin is used to detect such hemoglobin, it will be understood by those skilled in the art that detector 400 of the present invention could be applied to detect other blood constituents in plasma by varying the type of indicator paper used to form disk 460.
  • Hemolysis detector 500 is formed of chamber 510 which is enclosed on all sides except its bottom-most side 520. At the top of chamber 510, a sample injection port 530 is provided for receiving a whole blood sample into chamber 510.
  • a chamber base 540 is also provided. Both chamber 510 and chamber base 540 are preferably formed from molded plastic.
  • a microporous membrane disk 550 and an indicator paper disk 560 are also provided.
  • Membrane disk 550 is preferably formed from of a hydrophilic membrane such as Thermopor 800, Verapor 800, or Supor 800 made by Gelman Science, Inc.
  • indicator paper disk 560 is preferably formed of a porous paper impregnated with guaiac resin such as Hemoccult paper manufactured by SmithKline Diagnostics, Inc.
  • membrane disk 550 and indicator paper disk 560 in detector 500 have substantially the same diameter.
  • membrane disk 550 and indicator disk 560 are positioned between the top edge 570 of chamber base 540 and the bottom-most side 520 of chamber 510, and the top edge 570 of chamber base 540 and the bottom-most side 520 of chamber 510 are secured to each other with both disks in between, preferably by ultrasonic welding.
  • the preferred application of the device begins with the injection of one or two milliliters of a wetting agent (such as 15% isopropyl alcohol in water) into the chamber 510 through the sample injection port 530.
  • the injected wetting solution wets both the membrane disk 550 and the indicator paper disk 560, and most of the injection solution permeates out of the device within a minute.
  • a predetermined volume of a whole blood sample (preferably 1-10% of the internal volume of chamber 510) is injected into chamber 510 through sample injection port 530.
  • detector 500 is next inverted 180 degrees and one or two drops of developer solution are applied to the indicator paper disk 560.
  • the bottom of chamber base 540 is preferably open or exposed to the outside so as to allow the developer to be applied directly onto the indicator paper. If blue color appears in the area of the developer solution within approximately 30 seconds, this is an indication of free hemoglobin in the plasma and hemolysis is therefore detected as being present.
  • detector 500 Although in the embodiment of detector 500 described immediately above, the blood constituent of interest is free hemoglobin and an indicator paper impregnated with guaiac resin is used to detect such hemoglobin, it will be understood by those skilled in the art that detector 500 of the present invention could be applied to detect other blood constituents in plasma by varying the type of indicator paper used to form disk 560.
  • Hemolysis detector 600 is formed of chamber 610 which is enclosed on all sides except its bottom-most side 620. At the top of chamber 610, a sample injection port 630 is provided for receiving a whole blood sample into chamber 610.
  • a chamber base 640 is also provided. Both chamber 610 and chamber base 640 are preferably formed from molded plastic.
  • a microporous membrane disk 650 is also provided. Membrane disk 650 is the substantial equivalent of membrane disk 550 described above.
  • membrane disk 650 is positioned between the top edge 660 of chamber base 640 and the bottom-most side 620 of chamber 610, and the top edge 660 of chamber base 640 and the bottom-most side 620 of chamber 610 are secured to each other with the membrane disk in between, preferably by ultrasonic welding.
  • a wetting agent such as a normal saline or 15% isopropyl alcohol in water
  • the injected wetting solution wets the membrane disk 650, and most of the injection solution permeates out of the device within a minute.
  • a predetermined volume of a whole blood sample (preferably 1-10% of the internal volume of chamber 610) is injected into chamber 610 through sample injection port 630.
  • detector 600 is next inverted 180 degrees and a strip of indicator paper (such as guaiac paper) is wetted by bringing the indicator paper (not shown) into contact with side 670 of membrane disk 650.
  • the bottom of chamber base 640 is preferably open or exposed to the outside so as to allow the indicator paper to be brought into direct contact with the membrane disk.
  • One or two drops of developer solution are next applied to the indicator paper strip. If blue color appears in the area of the developer solution within approximately 30 seconds, this is an indication of free hemo lobin in the plasma and hemolysis is therefore detected as being present.
  • detector 600 Although in the embodiment of detector 600 described immediately above, the blood constituent of interest is free hemoglobin and an indicator paper impregnated with guaiac resin is used to detect such hemoglobin, it will be understood by those skilled in the art that detector 600 of the present invention could be applied to detect other blood constituents in plasma by varying the type of indicator paper used during operation of the system.
  • Hemolysis detector 700 is formed of chamber 710. At the top of chamber 710, a sample injection port 720 is provided for receiving a whole blood sample into chamber 710. A chamber base 730 is also provided. Both chamber 710 and chamber base 730 are preferably formed from molded plastic. A microporous membrane disk 740 is also provided on the bottom-most side of chamber 710. Membrane disk 740 is the substantial equivalent of membrane disk 550 described above. A channelling means 750 is positioned immediately below microporous membrane disk 740.
  • Channelling means 750 is substantially equivalent to channeling means 150, and thus collects the plasma portion of a whole blood sample as that plasma portion permeates through the membrane disk 740 and then channels that plasma portion to a clear capillary tube 760.
  • the bottom end 770 of capillary tube 760 is open.
  • membrane disk 740 and channelling means 750 are positioned between the chamber base 730 and the chamber 710, and the chamber base 730 and the chamber 710 are secured to each other with the membrane disk and channeling means in between, preferably by ultrasonic welding.
  • the preferred application of the device begins with the injection of one or two milliliters of a wetting agent (such as a normal saline or 15% isopropyl alcohol in water) into the chamber 710 through the sample injection port 720.
  • a wetting agent such as a normal saline or 15% isopropyl alcohol in water
  • the injected wetting solution wets the membrane disk 740, and most of the injection solution permeates out of the device within a minute.
  • a predetermined volume of a whole blood sample is injected into chamber 710 through sample injection port 720.
  • a strip of indicator paper (such as guaiac paper) is wetted by dropping plasma exiting from end 770 of tube 760 onto an indicator paper strip such as guaiac paper (not shown) .
  • indicator paper strip such as guaiac paper (not shown)
  • One or two drops of developer solution are next applied to the indicator paper strip. If blue color appears in the area of the developer solution within approximately 30 seconds, this is an indication of free hemoglobin in the plasma and hemolysis is therefore detected as being present.
  • an indicator paper is applied to plasma exiting tube 760 to determine whether hemolysis is present
  • an optical sensor system formed of a light transmitting source 780 and a light sensor 790
  • a light transmitting source 780 and a light sensor 790 may alternatively be used to analyze the plasma from tube 760 in order to determine whether hemolysis has occurred.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Ecology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

Procédé et appareil de détection d'hémolyse dans un échantillon de sang d'un patient. Une chambre hermétiquement fermée ayant un volume fixe est prévue pour recevoir l'échantillon de sang. Cette chambre a une pression interne due à la présence d'une quantité fixe d'air. Un volume de fluide que représente l'échantillon de sang est réceptionné dans la chambre hermétiquement fermée. Alors que l'échantillon passe dans ladite chambre, la pression interne de la chambre monte en retenant la quantité fixe d'air à l'intérieur de celle-ci au moment où le fluide arrive dans la chambre. L'augmentation de la pression interne fait passer la partie plasma de l'échantillon de sang se trouvant dans la chambre à travers une membrane qui forme au moins une partie d'un côté de la chambre. Un volume de test de la partie plasma de l'échantillon de sang est réceptionné par un dispositif de détection d'hémolyse après avoir traversé la membrane, et un état d'hémolyse est détecté d'après une teinte associée au volume de test réceptionné dans le dispositif de détection d'hémolyse.
EP96902156A 1995-01-25 1996-01-17 Detecteur d'hemolyse jetable Withdrawn EP0805981A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US37821095A 1995-01-25 1995-01-25
US378210 1995-01-25
PCT/US1996/000631 WO1996023223A1 (fr) 1995-01-25 1996-01-17 Detecteur d'hemolyse jetable

Publications (1)

Publication Number Publication Date
EP0805981A1 true EP0805981A1 (fr) 1997-11-12

Family

ID=23492210

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96902156A Withdrawn EP0805981A1 (fr) 1995-01-25 1996-01-17 Detecteur d'hemolyse jetable

Country Status (5)

Country Link
EP (1) EP0805981A1 (fr)
JP (1) JPH10513259A (fr)
AU (1) AU4657696A (fr)
CA (1) CA2211190A1 (fr)
WO (1) WO1996023223A1 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4210783B2 (ja) 2002-09-26 2009-01-21 アークレイ株式会社 分析用具
JP4262466B2 (ja) 2002-10-28 2009-05-13 アークレイ株式会社 分析用具および分析装置
EP2264453B1 (fr) * 2009-06-17 2013-04-03 Leukocare Ag Procédé de filtrage de sang
US8846333B2 (en) * 2010-06-10 2014-09-30 Hemcheck Sweden Ab Method and device for visual detection of hemolysis
JP5659960B2 (ja) * 2011-06-09 2015-01-28 コニカミノルタ株式会社 細胞平面展開方法
SE536634C2 (sv) 2011-12-09 2014-04-15 Hemcheck Sweden Ab Anordning för detektion av hemolys
GB2504138A (en) * 2012-07-20 2014-01-22 Emco Packaging Systems Ltd A self-contained, rapid field diagnostic system for blood samples
JP6357473B2 (ja) * 2012-08-08 2018-07-11 コーニンクレッカ フィリップス エヌ ヴェＫｏｎｉｎｋｌｉｊｋｅ Ｐｈｉｌｉｐｓ Ｎ．Ｖ． 一滴の血液を使用した血漿分離
DE102013205346A1 (de) 2013-03-26 2014-10-02 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Lanthanoidkomplexbasierte spektroskopische Hämoglobinbestimmung in einem flüssigen biologischen Medium
EP4465017B1 (fr) * 2014-09-30 2026-07-15 Siemens Healthcare Diagnostics Inc. Système et procédé de détection d'hémolyse

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4486536A (en) * 1982-05-28 1984-12-04 Smithkline Diagnostics, Inc. Specimen slide for occult blood testing
US4639316A (en) * 1984-12-14 1987-01-27 Becton, Dickinson And Company Automatic liquid component separator
ES2041668T3 (es) * 1986-10-29 1993-12-01 Asahi Medical Co., Ltd. Unidad de recogida de componentes de la sangre.
US4789526A (en) * 1986-12-15 1988-12-06 Pall Corporation Vacuum diagnostic device
US4995967A (en) * 1987-11-06 1991-02-26 Akzo N.V. Separator for cell-containing liquids
SE465355B (sv) * 1989-12-07 1991-09-02 Provivo Ab Engaangsfilter och foerfarande foer filtrering av en partikelbemaengd vaetskevolym
JP3003152B2 (ja) * 1990-03-20 2000-01-24 吉富製薬株式会社 遊離ヘモグロビンの測定法及びそれに用いる遊離ヘモグロビン測定用試薬キット
US5330420A (en) * 1992-01-13 1994-07-19 Therakos, Inc. Hemolysis detector
US5416026A (en) * 1993-10-04 1995-05-16 I-Stat Corporation Method for detecting the change in an analyte due to hemolysis in a fluid sample

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9623223A1 *

Also Published As

Publication number Publication date
JPH10513259A (ja) 1998-12-15
MX9705713A (es) 1997-10-31
CA2211190A1 (fr) 1996-08-01
WO1996023223A1 (fr) 1996-08-01
AU4657696A (en) 1996-08-14

Similar Documents

Publication Publication Date Title
US6659975B2 (en) Plasma collecting device
AU606917B2 (en) Blood separation system
US5919356A (en) Fluid sampling device
EP2264453B1 (fr) Procédé de filtrage de sang
JP2729503B2 (ja) 粒子分離法及び装置
JPH0455265B2 (fr)
US8158062B2 (en) Disposable fluid sample collection device
JP4229908B2 (ja) サンプラーキャップ
EP0552014B1 (fr) Détecteur d'hémolyse
US4172448A (en) Fluid sampling device
KR20150039051A (ko) 혈액으로부터 혈장 또는 혈청을 분리하는 혈액 필터 장치 및 그의 용도
WO1996023223A1 (fr) Detecteur d'hemolyse jetable
US5820825A (en) Waste container for portable blood analyzer
JP2000189405A (ja) 血液濾過ユニット
JP2000074906A (ja) 簡易血液濾過点着器
JP2008279195A (ja) 血液分離フィルタ装置
JP7825703B2 (ja) 流体試料採取装置から液体試料分析器へ流体試料を移送するための装置および方法
JP2001321367A (ja) 血漿又は血清採取具
JP2004325412A (ja) 血液検査用容器
MXPA97005713A (en) Disposable detector of hemoli
US20260118257A1 (en) Apparatus and method for testing blood
SE2050749A1 (en) Collection device for bodily fluid samples
CA3278414C (fr) Appareil et procédé d'analyse de sang
CN117813502A (zh) 用于将流体样本从流体样本收集设备转移到液体样本分析器的设备和方法
CA3278414A1 (fr) Appareil et procédé d'analyse de sang

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19970813

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: SI PAYMENT 970813

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19990803