CA2025055A1 - Capillary tube for taking blood samples - Google Patents
Capillary tube for taking blood samplesInfo
- Publication number
- CA2025055A1 CA2025055A1 CA002025055A CA2025055A CA2025055A1 CA 2025055 A1 CA2025055 A1 CA 2025055A1 CA 002025055 A CA002025055 A CA 002025055A CA 2025055 A CA2025055 A CA 2025055A CA 2025055 A1 CA2025055 A1 CA 2025055A1
- Authority
- CA
- Canada
- Prior art keywords
- capillary tube
- cell
- capillary
- measuring
- blood
- 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.)
- Abandoned
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150015—Source of blood
- A61B5/150022—Source of blood for capillary blood or interstitial fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150343—Collection vessels for collecting blood samples from the skin surface, e.g. test tubes, cuvettes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- 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
- G01N21/03—Cuvette constructions
-
- 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
- G01N33/4905—Determining clotting time of blood
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- 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
- G01N21/03—Cuvette constructions
- G01N2021/0346—Capillary cells; Microcells
Abstract
A capillary tube for taking capillary blood samples for a system for measuring the coagulation time.
In order to reduce the risk of infection for the laboratory staff and to simplify the work of taking and processing the capillary blood samples, the capillary tube is made of plastic and a lyophilizate (14, 15, 16) is approximately uniformly distributed in its interior and along its entire length, the lyophilizate being obtained by freeze-drying a mixture containing an anti-coagulant and at least one high-molecular additive.
In order to reduce the risk of infection for the laboratory staff and to simplify the work of taking and processing the capillary blood samples, the capillary tube is made of plastic and a lyophilizate (14, 15, 16) is approximately uniformly distributed in its interior and along its entire length, the lyophilizate being obtained by freeze-drying a mixture containing an anti-coagulant and at least one high-molecular additive.
Description
2 ~ 3 The invention relate~ more particularly to a capillary tube for taking capillary blood samples and a method of manufac~uring it.
The invention also relates to a device for mea~uring the coagulation time of a capillary blood sample, the device containing a capillary tube according to the invention and a cell for photometric measurement of the coagulation time of a blood ~ample, the cell bein~ made of plastic and its top part being divided by a partition into two compartments and the partition having a ~harp edge aS
a distance from the base of the cell. A cell of this kind and an automatic method of measuring the coagulation time are described in US-PS 4 659 550.
The met~od used hitherto for taking and preparing a capillary blood sample before measuring the coagulation time by the conventional microquick method involve6 a number of stages and requires a relatively large amount of wo~k and time compared with the measurement which i6 usually made automatically. The method used hitherto for taking and ereParing the sample comprises e.g. the following steps:
. ~ .
an~anti-clotting solution, e.g. a ciltrate solution, is drawn into a capillary up to the O.OOS ml mark, - a drop of blood i8 taken from a finger by pricking with a lancet and the operator orally pipettes blood into the capillary containing the citrate solution up to the 0.050 ml mark, Ve/26.7.90 2~2)~
- the operator then immediately blows the contents of the capillary into the bottom of a glas~ or plastic tube, and - ~he ~ube is then moved in a circle in order to mix the blood sample more thocoughly with the citrate solution.
In previous methods of measurement, it has been conventional for the processed mixture of a blood sample and a citrate solution to be orally pipetted into the mea6uring cell. Oral pipetting, however, carries an appreciable risk of infecting the operator.
~n this connection it is pointed out that US-PS
4 756 884 discloses a test device in which, inter alia:
- a liquid sample i6 sucked by the capillary force exerted by a caeillary tube, - the capillary force is u~ed to mix the sucked sample with a reagent contained in the capillary tube, and - a reagent is used in the form of a soluble gel or sponge contained in the test device.
According to US-PS 4 756 884, ~he reagent used in the test device is present in only a very small region thereof. It is therefore impossible for all of the blood sample in the test device to be efficiently, i.e.
uniformly, mixed with the reagent by capillary force. The teaching in US-PS 4 756 884 is therefore unsuitable for the preparation of a blood sample before measurement of the blood coagulation time, when the blood sample first has to be mixed with an anticoagulant. During the preparation process it is very important to obtain a uniform mixture of the complete blood sample with the :: ::: - , 2 ~ 2 ~r antieoagulant. If this is not done part of the blood sample can coagulate, i.e. form a clot, befo~e b~ing introduced into the measuring cell. In this case the accuracy and even the reliability of the measurement will be veLy doubtful.
The main objec~ of the invention therefore is to construct a device for eliminating ~he aforementioned disadvantage6 of the known devices, a particular object being to considerably reduce the risk of infecting the laboratory staff and greatly to simplify the wsrk of taking and processing the blood sample6 and mea~uring the coagulation time.
According to the invention, the problem is solved mainly by a capillary tube which (a) is made of a plastic and --(b) has a lyophilizate approximately uniformly di~tributed in its interior and over its entire lenqth, the lyophilizate being obtained by freeze-drying a mixture containing an anticoagulant and at least one high--molecular additive.
By means of the capillary force produced by the capillaey tube according to the invention, the entire volume of blood ~ample sucked into the capillary tube is uniformly mixed with the anticoagulant therein. Thi~s ensures that no part of the sample can coagulate before being introduced into the cell for measucing the coagulation time.
The lyophilizate in the capillary tube increases the capillary suction force at the beginning of the ~uction process when taking the blood sample. The lyophilizate therefsre assists the capillary force generated by the capillary tube, for the purpose of uniformly mixing the blood sample with the anticoagulant and completely filling the capillary ~ube with the blood sample and the lyophilizate dissolved therein. Since the capillary tube is filled completely, the quantitative ratio of sample to anticoagulant is exactly defined. The aforementioned two effects can increase the reliability with whicb the coagulation time is measured.
The capillary tube according to the invention also greatly simplifies the process of sampling blood and preparing it before measuring the coagulation time, and in a manner which considerably reduces the risk of infecting the operator.
The invention also relates to a method of manufacturing a capillary tube according to the invention.
The method comprises (a) filling the entire interior of a plastic capillary tube with a liquid mixture containing an anti-coagulant and at least one high-molecular additive, and (b) f~eeze-drying the mixture in the interior of the capillary tube.
By means of the method of manufacture defined herein-before, the anticoagulant is uniformly distributed overthe entire length of the capillary tube. Consequently, by the action of capilla~y force alone, the entire volume of sample sucked into the capillary tube is uniformly mixed with the anticoagulant therein.
The invention also covers a device for measuring the coagulation time of a capillary blood sample, the device ~ . ~ . . . ~ ; .
containing a cell for photometric measurement of the coagulation time of a blood sample, the cell being made of plastic and its top part being divided by a partition into two compartments and the partition having a sharp edge at a di~tance from the base of the cell. According to the invention the device (a) contains a capillary tube according to the invention and a matching cover for closing one end of the capillary tube, and (b~ the top pace of the cell has a holder for receiving the capillary tube and in which the capillary tube can be so disposed parallel to the longitudinal direction of the cell that a part of the capillary tube projects from the cell.
The device according to the invention defined herein-before has all the advantages of the capillary tube ~hecein and, more particularly, greatly simplifies the taking and preparation of a blood sample for measuring the coagulation time, and in a manner which greatly reduces the risk of infecting the operator.
ln a preferred embodiment of the device defined hereinbefore, the holder is so constructed that the capillary tube can be operatively connected by the holder to the cell. This facilitates use of the device. In a preferred embodiment of the device defined hereinbefore, the cover is made of a deformable material and has a cavity which contains a volume of air even after the cover has been placed on one end of the capillary tube.
An embodiment of the invention will now be described with re~erence to the accompanying drawings, in which:
~ 3~''3 Figs. 1-3 show cross-sections of three capillary tubes 11, 12, 13 according to the invention. in each -case in closs-section along the longitudinal axis of the capillaLy tube and in cro6s ~ection along line I-I;
Fig. 4 i6 a ~lan view of a mea~uring cell 41 containing a capillary tube 81 accordinq to the invention: ' Fig. 5 is a cro6s-section through the arrangement in Fig. 4 along line V-V in Fig. 4;
15 Fig. 6 is a cross-~ection through the arrangement in Fig. 4 along line VI-VI in Fig. 4;
Fig. 7 shows vithdrawal of a blood sample 49 using the capillary tube 81 in the arrangement in Figs. 4-6:
Fig. 8 is a cross-section of the measuring .
arrangement in Figs. 4-6, the end of the capillary tube 81 which project6 after sample-taking as in Fig. 7 being closed by a cover 82 ~: i Fiq. 9 i6 a diagram of the measuring cell and the elctro-optical arrangement of a known device 30~ for measuring the coagulatio~ time: ~ ~
Fig. 10 is a cros6-section of the cell 1 in Fig. 9 and an associated arrangement 21 foc eroducing a variable air pres~ure in the cell;
Fig. 11 is a diagrammatic representation of steps (1)-(4) carried out when using the device in Fig. 9 for measuring the coagulation time .
' _ 7 _ 202~0~
Figs. 12-14 show use of the cell 41 in Figs. 4-6 in a measuring device a~ pec Figs. 9 and 10;
Fig. 15 is a diagrammatic cross-section of a preferred embodiment of the arrangement shown in Fig. 10 for producing a variable air prçssure;
Fig. 16 is a diagram of a typical curve of the air pressure obtainable by the arrangement in Fig. 15:
~ig. 17 6hows the cocrelation between results obtained by a conventional microquick method and cesults obtained by a plasmaquick method, and ' ~:
Fig. 18 shows the correlation between results obtained by a microquick method according to the invention and results obtained by a `~ 20 plasmaquick method.
Figs. 1-3 show cross-sections of three capillary tube6 ~ 11, 12, 13 according to the invention for taking blood `~ samples for a system for measuring the coagulation time.
Figs. 1-3 each show a cross-section along the longitudinal axis of one of the capillary tubes and a cross-section in a plane at right angles to the longitudinal axis of the capillary tube (shown by line I-I).
~mpty capillary tubes 11. 12, 13 are available commercially and are called end-to-end capillaries. The capillarie~ are preferably made of polyethylene ~PE) or another suitable plastic. e.g. eolypropylene (PP).
polyvinyl chloride (PVC) or polycarbonate (PC).
Depending on the desired volume. the capillary tube6 11. 12, 13 have the following dimensions:
- ~
2 ~
VolumeLengthOuter diameterInner diameter rmicrolitres] [mml rmm~ ~mml 3~ 1.78-1.805 1.05-1.08 1.785-l.B2 1.10-1.11 ~0 30 2.10-2.14 1.25-1.30 2.38-2.43 1.41-1.43 A lyophilizate 14, 15, 16 i8 distributed approximately uniformly over the entire length of the interior of each capillary tube 11, 12, 13, the lyophilizate being obtained by lyophilization. i.e. freeze-drying of a liquid mixture containing an anticoagulant, i.e. an anti-clotting substance, and at least one high-molecular additive used as an excipient for the anticoagulant.
A capillary tube according to the invention is made by filling its entire interior with a liquid mixture containing an anticoagulant and at least one high--molecular additive as an excipient. The mixture is then freeze-dried in the interior of the capillary tube. A
lyophilizate 14. 15, 16 is f ormed by f reeze-drying in each capillary tube. In the process, empty spaces 17, 18, 19 are produced in the capillary tubes.
The method of producing the lyophilizate in the capillary tubes compcises the following step6:
1. The solution for filling the capillary tube is pLepared. Its composition is e.g. as follows:
- 0.011 molJl Trisodium eitrate - 3.000 g/l Gelatine 2. A number of capillary tubes are completely filled with solution by immersion therein.
2 ~ 3 3. The capillary tubes filled with solution are placed hori20ntally in a pre-cooled elate of a lyophilizer and left there for at lea~t 15 minutes, thus rapidly freezing the solution in the capillary tubes. The tempe~ature of the pre-cooled plate must be lower than _35C.
The invention also relates to a device for mea~uring the coagulation time of a capillary blood sample, the device containing a capillary tube according to the invention and a cell for photometric measurement of the coagulation time of a blood ~ample, the cell bein~ made of plastic and its top part being divided by a partition into two compartments and the partition having a ~harp edge aS
a distance from the base of the cell. A cell of this kind and an automatic method of measuring the coagulation time are described in US-PS 4 659 550.
The met~od used hitherto for taking and preparing a capillary blood sample before measuring the coagulation time by the conventional microquick method involve6 a number of stages and requires a relatively large amount of wo~k and time compared with the measurement which i6 usually made automatically. The method used hitherto for taking and ereParing the sample comprises e.g. the following steps:
. ~ .
an~anti-clotting solution, e.g. a ciltrate solution, is drawn into a capillary up to the O.OOS ml mark, - a drop of blood i8 taken from a finger by pricking with a lancet and the operator orally pipettes blood into the capillary containing the citrate solution up to the 0.050 ml mark, Ve/26.7.90 2~2)~
- the operator then immediately blows the contents of the capillary into the bottom of a glas~ or plastic tube, and - ~he ~ube is then moved in a circle in order to mix the blood sample more thocoughly with the citrate solution.
In previous methods of measurement, it has been conventional for the processed mixture of a blood sample and a citrate solution to be orally pipetted into the mea6uring cell. Oral pipetting, however, carries an appreciable risk of infecting the operator.
~n this connection it is pointed out that US-PS
4 756 884 discloses a test device in which, inter alia:
- a liquid sample i6 sucked by the capillary force exerted by a caeillary tube, - the capillary force is u~ed to mix the sucked sample with a reagent contained in the capillary tube, and - a reagent is used in the form of a soluble gel or sponge contained in the test device.
According to US-PS 4 756 884, ~he reagent used in the test device is present in only a very small region thereof. It is therefore impossible for all of the blood sample in the test device to be efficiently, i.e.
uniformly, mixed with the reagent by capillary force. The teaching in US-PS 4 756 884 is therefore unsuitable for the preparation of a blood sample before measurement of the blood coagulation time, when the blood sample first has to be mixed with an anticoagulant. During the preparation process it is very important to obtain a uniform mixture of the complete blood sample with the :: ::: - , 2 ~ 2 ~r antieoagulant. If this is not done part of the blood sample can coagulate, i.e. form a clot, befo~e b~ing introduced into the measuring cell. In this case the accuracy and even the reliability of the measurement will be veLy doubtful.
The main objec~ of the invention therefore is to construct a device for eliminating ~he aforementioned disadvantage6 of the known devices, a particular object being to considerably reduce the risk of infecting the laboratory staff and greatly to simplify the wsrk of taking and processing the blood sample6 and mea~uring the coagulation time.
According to the invention, the problem is solved mainly by a capillary tube which (a) is made of a plastic and --(b) has a lyophilizate approximately uniformly di~tributed in its interior and over its entire lenqth, the lyophilizate being obtained by freeze-drying a mixture containing an anticoagulant and at least one high--molecular additive.
By means of the capillary force produced by the capillaey tube according to the invention, the entire volume of blood ~ample sucked into the capillary tube is uniformly mixed with the anticoagulant therein. Thi~s ensures that no part of the sample can coagulate before being introduced into the cell for measucing the coagulation time.
The lyophilizate in the capillary tube increases the capillary suction force at the beginning of the ~uction process when taking the blood sample. The lyophilizate therefsre assists the capillary force generated by the capillary tube, for the purpose of uniformly mixing the blood sample with the anticoagulant and completely filling the capillary ~ube with the blood sample and the lyophilizate dissolved therein. Since the capillary tube is filled completely, the quantitative ratio of sample to anticoagulant is exactly defined. The aforementioned two effects can increase the reliability with whicb the coagulation time is measured.
The capillary tube according to the invention also greatly simplifies the process of sampling blood and preparing it before measuring the coagulation time, and in a manner which considerably reduces the risk of infecting the operator.
The invention also relates to a method of manufacturing a capillary tube according to the invention.
The method comprises (a) filling the entire interior of a plastic capillary tube with a liquid mixture containing an anti-coagulant and at least one high-molecular additive, and (b) f~eeze-drying the mixture in the interior of the capillary tube.
By means of the method of manufacture defined herein-before, the anticoagulant is uniformly distributed overthe entire length of the capillary tube. Consequently, by the action of capilla~y force alone, the entire volume of sample sucked into the capillary tube is uniformly mixed with the anticoagulant therein.
The invention also covers a device for measuring the coagulation time of a capillary blood sample, the device ~ . ~ . . . ~ ; .
containing a cell for photometric measurement of the coagulation time of a blood sample, the cell being made of plastic and its top part being divided by a partition into two compartments and the partition having a sharp edge at a di~tance from the base of the cell. According to the invention the device (a) contains a capillary tube according to the invention and a matching cover for closing one end of the capillary tube, and (b~ the top pace of the cell has a holder for receiving the capillary tube and in which the capillary tube can be so disposed parallel to the longitudinal direction of the cell that a part of the capillary tube projects from the cell.
The device according to the invention defined herein-before has all the advantages of the capillary tube ~hecein and, more particularly, greatly simplifies the taking and preparation of a blood sample for measuring the coagulation time, and in a manner which greatly reduces the risk of infecting the operator.
ln a preferred embodiment of the device defined hereinbefore, the holder is so constructed that the capillary tube can be operatively connected by the holder to the cell. This facilitates use of the device. In a preferred embodiment of the device defined hereinbefore, the cover is made of a deformable material and has a cavity which contains a volume of air even after the cover has been placed on one end of the capillary tube.
An embodiment of the invention will now be described with re~erence to the accompanying drawings, in which:
~ 3~''3 Figs. 1-3 show cross-sections of three capillary tubes 11, 12, 13 according to the invention. in each -case in closs-section along the longitudinal axis of the capillaLy tube and in cro6s ~ection along line I-I;
Fig. 4 i6 a ~lan view of a mea~uring cell 41 containing a capillary tube 81 accordinq to the invention: ' Fig. 5 is a cro6s-section through the arrangement in Fig. 4 along line V-V in Fig. 4;
15 Fig. 6 is a cross-~ection through the arrangement in Fig. 4 along line VI-VI in Fig. 4;
Fig. 7 shows vithdrawal of a blood sample 49 using the capillary tube 81 in the arrangement in Figs. 4-6:
Fig. 8 is a cross-section of the measuring .
arrangement in Figs. 4-6, the end of the capillary tube 81 which project6 after sample-taking as in Fig. 7 being closed by a cover 82 ~: i Fiq. 9 i6 a diagram of the measuring cell and the elctro-optical arrangement of a known device 30~ for measuring the coagulatio~ time: ~ ~
Fig. 10 is a cros6-section of the cell 1 in Fig. 9 and an associated arrangement 21 foc eroducing a variable air pres~ure in the cell;
Fig. 11 is a diagrammatic representation of steps (1)-(4) carried out when using the device in Fig. 9 for measuring the coagulation time .
' _ 7 _ 202~0~
Figs. 12-14 show use of the cell 41 in Figs. 4-6 in a measuring device a~ pec Figs. 9 and 10;
Fig. 15 is a diagrammatic cross-section of a preferred embodiment of the arrangement shown in Fig. 10 for producing a variable air prçssure;
Fig. 16 is a diagram of a typical curve of the air pressure obtainable by the arrangement in Fig. 15:
~ig. 17 6hows the cocrelation between results obtained by a conventional microquick method and cesults obtained by a plasmaquick method, and ' ~:
Fig. 18 shows the correlation between results obtained by a microquick method according to the invention and results obtained by a `~ 20 plasmaquick method.
Figs. 1-3 show cross-sections of three capillary tube6 ~ 11, 12, 13 according to the invention for taking blood `~ samples for a system for measuring the coagulation time.
Figs. 1-3 each show a cross-section along the longitudinal axis of one of the capillary tubes and a cross-section in a plane at right angles to the longitudinal axis of the capillary tube (shown by line I-I).
~mpty capillary tubes 11. 12, 13 are available commercially and are called end-to-end capillaries. The capillarie~ are preferably made of polyethylene ~PE) or another suitable plastic. e.g. eolypropylene (PP).
polyvinyl chloride (PVC) or polycarbonate (PC).
Depending on the desired volume. the capillary tube6 11. 12, 13 have the following dimensions:
- ~
2 ~
VolumeLengthOuter diameterInner diameter rmicrolitres] [mml rmm~ ~mml 3~ 1.78-1.805 1.05-1.08 1.785-l.B2 1.10-1.11 ~0 30 2.10-2.14 1.25-1.30 2.38-2.43 1.41-1.43 A lyophilizate 14, 15, 16 i8 distributed approximately uniformly over the entire length of the interior of each capillary tube 11, 12, 13, the lyophilizate being obtained by lyophilization. i.e. freeze-drying of a liquid mixture containing an anticoagulant, i.e. an anti-clotting substance, and at least one high-molecular additive used as an excipient for the anticoagulant.
A capillary tube according to the invention is made by filling its entire interior with a liquid mixture containing an anticoagulant and at least one high--molecular additive as an excipient. The mixture is then freeze-dried in the interior of the capillary tube. A
lyophilizate 14. 15, 16 is f ormed by f reeze-drying in each capillary tube. In the process, empty spaces 17, 18, 19 are produced in the capillary tubes.
The method of producing the lyophilizate in the capillary tubes compcises the following step6:
1. The solution for filling the capillary tube is pLepared. Its composition is e.g. as follows:
- 0.011 molJl Trisodium eitrate - 3.000 g/l Gelatine 2. A number of capillary tubes are completely filled with solution by immersion therein.
2 ~ 3 3. The capillary tubes filled with solution are placed hori20ntally in a pre-cooled elate of a lyophilizer and left there for at lea~t 15 minutes, thus rapidly freezing the solution in the capillary tubes. The tempe~ature of the pre-cooled plate must be lower than _35C.
4. Freeze-drying i6 carried out in a conventional lyophilize~, which can preferably be automatically con~rolled. In the lyophilizer, lyophilization occurs -in two steps, i.e. primary drying (sublimation) followed by secondary drying. Primary drying is carried out at a pressure of 400 microbars for 12 hour~, during which the temperature of the product is below -20C for at least 6 hours. Secondary drying is carried out at a pressure of 50 microbars for at least 4 hour6, during which the temperature of the product i~ +350C.
The anticoagulant is preferably trisodium citrate at a concentration of 0.011 mol/l. Other suitable anti-coagulants are ethylene diamine tetraacetic acid di60dium salt (EDTA) or sodium fluoride. The substance used as an anticoagulant is placed in an aqueous ~olution, the 25 concentration being one-tenth of the corresponding concentration of venous blood 6ampling.
The excipients for the anticoagulant are preferably high~molecular additive6 such as fibrinogen`of bovines or 30 aqueous gelatine. Alternatively the excipient can e.g. by human fibrinogen, bovine albumin, polyethylene glycol PEG 8000 or polyvinyl pyrolidone 20 or 30. The excipients are used in the form of aqueous solutions, preferably at a concentration of 0.1 to 3.0%.
A capillary tube according to the invention as per Figs. 1-3 is preferably used in combination with a ., ..... : . : ........... .- : ... .~ : .... :, : . :: - :-, : :: ...... ::: .,: . " ., .. ~ .... . .
:, , - 2 ~ F~
matching test cell in a device for measuring the coagulation time of a blood sample. A measuring cell suitable for the purpose will now be described with reference ~o Figs. 4-6.
Fig. 4 is a plan view of a measuring cell 41 containing a capillary tube 81 according to the invention.
Fig. 5 shows a cross-section of the arrangement in Fig. 4 through line V-V in Fig. 4. Fig. 6 ~hows a cros6-section 10 of the aIransement in Fig. 4 through line VI-VI in Fig. 4.
The measuring cell 41 is made of material, e.g. a suitable plastic, for making optical, preferably photo-metric, measurements. Cell 41 need not necessarily have the shape shown in Figs. 4-6, but it is important for it to have a partition 44 having a sharp edge 43 at a distance from the bottom. ~he partition divides the top part of the cell into two compartments 7 and 8. As Fig. 6 shows, the top part of cell 41 has a holder 91 for 20 receiving a caeillary tube 81 according to the invention.
The capillary tube 81 i8 disposed in holder 91, preferably parallel to the longitudinal direction of cell 41, 60 that a part of the capillary tube projects from the cell.
Holder 91 is preferably constructed 60 that it can non-25 -positively connect the caeillary tube 81 to the cell 41.
Fig. 7 shows a blood sample 49 taken by a capillary tube al according to the invention and disposed in a measuring cell 41 as described. A patient's finger-tip i~
30 punctured with a lancet and a drop of blood flows out and is used for testing. The preset quantity of blood (10 to 50 microlitres) is drawn up through a capillary tube according to the invention, by holding the tube horizontal and keeping the tip in the droplet of ou~flowing blood.
~5 When sampled in this way, the blood is drawn into the capillary tube according to the invention, exclusively by the capillary force produced in the tube.
," . . ~ : , . - , . ' ' ' ~ . . ! : , ' . ' : . : ' ; . , ' , . ' ' , . . ' ': ' , , 202~ '3 As shown in Fig. 8, immediately after sampling the blood the end of the capillary 81 projecting from the cell 41 is closed by a cover 82. The cove~ is preferably made of a soft defo~mable material, e.g. bromobutyl rubber, and has a cavity 83 which contains a volume of air even after the cover has b2en placed on one end of the capillary tube.
The sample in the capillary tube 81 i6 transferred to the measuring cell 41 by a pressure surge produced by placing the cover on one end of the capillary tube. The sample is transfe~red mainly by gravity if the capillary tube is moved from the horizontal sampling position into a vertical position, when the sample flows from the capillary tube 81 and is received in the bottom part of the measu~ing cell 41. In orde~ to deliver all the sample from the capillary tube into the mea~uring cell 41, the ~op part of the cover 82 containing the cavity 83 is 20 pressed by the fingers. The resulting pressure surge ~.
ensures that the complete sample i8 transferred to the measuring cell. This is important for reproducing the measurements.
After the sample has been transferred to the measuring cell as aforementioned, the empty capillary tube. with or without a cover. can be le~t in the cell or removed theref~om, The measuring cell is then placed in a device for measuring the coagulation time. The construction and operation o$~this device will now be described with reference to Figs. 9 to 18. These drawings do not show the capillary tube according to the invention, because it is not necessary for the actual photometric measurement of the coagulation time.
Fig. 9 shows a measuring cell 1 inserted into the measuring device, and diagrammatically shows the electro--: ? ~
-optical arrangement of the measucing device. Cell 1 does not have the ame shape as cell 41 in Figs. 4-6, but basically has a very similar 6~ructure. Cell 1, like the cell 41 in Figs. 4-6, has a partition 2 which divides the top part of the cell into two compartments 7 and 8, and a sharp edge 3 at a distance from the base of the cell.
Fig. 9 shows an electro-optical arrangement comprising a light ~ource 5, e.g. a light-emitting diode, and a light receiver 6, e.g. a photodiode, in the arrangement shown.
These components produce and receive a light beam 4 which travels through the cell, ea6sing near and below the edge 3 in order to measure the extinction of the contents of the cell detected by light beam 4. The path of beam 4 is chosen so that the beam detects a clot 39 formed at edge 3.
The electro-optical arrangement also contains a light --source 62, e.g. a light-emitting diode 62, and a light receiver 63, e.g. a photodiode 63, in the arrangsment shown. These component produ~e and receive a light beam 61 which travels through the cell, passing above edge 3, in order to measure the extinction of the contents of the sell detected by light beam 61. The path of beam 61 is chosen so that it does not detect the maximum preset amount of sa~ple inteoduced into the cell, but so that after a reagent for measuring the coagulation has been added, the light beam 61 detect~ the mixture of sample and reagent, even at the minimum preset volume.
~ ' In order to reduce the influence of environmental light on the extinction measurements by light beams 4 and 61, the light receivers 6 and 63 are preferably photo-diodes with built-in infrared filter~ having a pass band of about 900 to about 100 nm and a minimum attenuation of about 9940 nm. By this means the sensitivity of the measurements to environmental incande~cent lamp illumination is reduced e.g. by about a factor of 5.
'.' ~" , : ' 2 ~ 2 ~j O ~ ~3 As Fig. 10 shows. the compartment 7 in the top part of cell 1 is connected through an opening 9 to an arrangement 21 for generating a variable air pres6ure acting on the contents of the cell. The pressure moves the mixture of sample and reagent in the device according to the invention in a manner described hereinafter with reference to Fig. ll ~3). As described hereinafter with reference to Figs. 15 and 16, the arrangement 21 can contain a pump element in the form e.g. of a vibrating diaphragm 22. The resulting air pressure travel~ through a duct 23 and opening 19 into cell 1. The cell has an opening 10 which remains open during operation.
lS As shown in Fig. 11, the following step6 are carried out when the cell according to the invention is u6ed to measure the coagulation time of a blood sample.
(1) The preset 6tarting volume of prepaced blood or plasma ~ample 31 is delivered from a capillary tube such as 81 in Fig. 8 and received in the bottom part of cell 1, where it is incubated. ~s shown in Fig. 11, the chosen amount of sample is preferably too small to reach the edge 3. 80 that air can flow freely between edge 3 and the surface of the sample. In this manner the air pressure generated by arrangement 21 cannot move the sample, and the sample remains motionless until the preset quantity of reagent has been introduced into the cell.
(2) The preset starting volume of reagent is introduced into the cell. The mixture of sample and reagent is chosen so that the surface thereof always lies above the edqe 3 and the light beam 61. The effects. as soon as the reagent has been introduced into the cell, are as follows:
: ::
202~r . .
(3) The mixeure 32 of sample and reagent is detected by the light beam 61. This time marks the beginning of the measurement of the coagulation time. This time i~
registered by known electronic 6ignal-proce~sing means. As a result of the air pre~cure produced by the aforementioned means shown in Fig. 10, the sample--reagent mixture now flow~ and moves in reciprocation between po6itions (a) and (b) shown in Fig. 11 (3). As a re6ult the sample is thoroughly mixed with the reagent and the mixture flows ~ound the sharp edge 3 of the cell.
(4) As a result of the movement of the liquid relative to -edge 3 as shown in (3), a clot 33 form~ at edge 3 at the instant of coagulation. Since this clot is detected by light beam 4, there i8 a sudden, marked change in the extinction measured by the beam. The time when coagulation occurs, i.e. the coagulation ~; 20 time, is unambiguously and accurately measured by de~ermining this chanqe. The determination i8 made and the values are displayed by known electronic signal- -erocessing and data display means.
As a variant of the last-described method, and provided the measurement is not adversely affected, the ; ~-sample can be made big enough for its surface to lie above ~-edge 3 even when the cell contains the sample only. In this case, before the reagent i~ added, the sample i8 30 ~ detect,ed by the lightl beam 4 and moved by the afore-mentioned air pressure, in the manner shown for the sample-reagent mixture in Fig. 11 (3).
Figs. 12 to 14 illustrate use of the cell 41 in Figs.
4-6 in a measuring device as per Figs. 9 and 10.
-~.
2 0 2 ~
As shown in Fig. 12, the cell 41 is supplied with a variable air pressure through a side opening 42, which is connected by a line 77 to the aic-pre6surizing arrangement.
Fig. 13 shows cell 41 where it contains the ~ample only. Fig. 14 shows 41 when it contain~ the mixture of sample and reagent. In Fig6. 13 and 14 the positions of light beam 4 and 61 are marked by small circles.
In Figs. 13 and 14, the cell 41 is used in the same manner as described with reference to Fig. 11.
Fig. 15 is a diagrammatic cross-section through a preferred embodiment of the arrangement 21 (in Fig. 10) for producing the variable air pres6ure. The arrangement is contained in a casing 71, in which a diaphragm 72 is disposed and has a laminated icon core 73. The diaphragm 72 is vibrated by an electromagnetic drive device containing a magnetic corA 74 and a magnetic coil 75 and supelied with a suitable a.c. As a result a variable air eressure is eroduced in casing 71 and is supplied through lines 77 and 78 to the two cells in the device accordinq to the invention.
~ '', Fig. 16 is a diagram of a typical time curve of the air pre~sure obtainable by the device shown in Fig. lS.
The air eressure varies between ~2 and -2 millibars, and varies approximately in the form of a sine curve 06cillatinq a frequency of 40 Hz.
On the basis of the measured results presented in Figs. 17 and 18 it will be demonstrated hereinafter that when the blood sample is taken and processed by a capillary tube according to the invention in a microquick 35 erocess for measuring the coagulation time, the correlation achieved with correseonding results from a ::
- ~21~3~
plasmaquick method, such results being recognized as accurate and reliable, i5 better than when the blood sample is taken and processed by the conventional method described in the opening part of this description.
It will be appreciated at this point that in the aforementioned processes there are considerable differences in the method of taking and processing the samQle for determining the coagulation time. This will be evident from the following description of these processes.
The Pla6maquick Process The plasmaquick process is a method of determining the lS thromboplastin time, using venous citrate plasma. In the conventional plasmaquick process, plasma is obtained by the following procedure:
U6ing a sterile plastic 2 ml throwaway syringe 20 containing exactly 2 ml of sterile 0.1 mol/l sodium citrate solution, blood is drawn from a vein puncture up ~ to the 2.0 ml mark, the plunger is retracted and the ; contents i8 quickly and completely mixed by repeatedly inclining the syringe. The citrate blood is centrifuged at 25 3000 rpm (about 1600 g) for 15 minutes.
: - :
The coagulation measurements should be made immediately if possible, but always within two hours after sampling the blood. The resulting plasma is kept in 30 throwaway plastic tubes at 15-25C.
The coagulation time is measured e.g. with the <COBA5>
Fibro device, the ba6ic construction and operation of which have already been described with reference to Figs.
35 9-16. A <COBAS> Fibro measuring cell, automatic micro- ~ -pipettes for volumes of 100 and 200 microlitres and a ' ' ' ' ' '' ~ : . .' . ~ : ., :. '~:: '. .: . . :'.: :, : . : :: , - `` 2 ~ 2 '3 ~
stop-watch ace also required ~or the meaæurement with <COBAS~ Fibco. Befoire making the measurement, a volume of 0.1 ml of the plasma obtained by the aforegoing procedure is pre-heated at 37C for 2 minute~, uæing a preheated cell and the <COBAS> Fibro unit heater. 0.2 ml of reagent solution is then added, after which the measurement iæ
made in the manner desccibed with reference to Figæ. 9-16.
The conventional microquick Proce6s The conventional microquick process is a method of determining the thromboplastin time using capillairy citrate blood. In the conventional microquick process, the blood æample is taken and prepared as follows before measuring the coagulation time:
:: :
1. Draw citrate solution into a capillary up to the 0.005 ml mark.
2. Clean finger (preferably middle or ring finger of left hand) with alcohol and prick with a lancet. Wash off the firæt dropæ of blood.
25 3 Pour blood up to the 0.050 ml mark into the capillary y~ containing citrate solution. Blow out immediately into a glaæs oc plastic tube or directly into the bottom of the mea~uring cell of a coagulation-time measuring device (avoid foaming) and mix by moving it in a circle. ~ , i~
4. Measure the coagulation within lO minutes if possible, but never later than 60 minutes after sampling the ;~ blood, and the citrate blood must never be left in the `~ 35 capillary, '~ ' ' : .
, ~:
The coagulation time is measured e.g. with a <COBAS~ -Fibro measuring device, the basic construction and operation of which have already been described with reference to Figs. 9-16. A <COBAS> Fibro measuring cell, an automatic micropipette for a volume of e.g. 50 microlitres and a stop-watch are required for making measurement6 with <COBAS> Fib~o. Before making the measurement, a volume of 0.050 ml of the capillary citrate blood obtained by the aforementioned procedure i~ pre--heated at 37C for 2 minutes u~ing the <COBAS> Fibro unit heateI. 0.050 ml of reagent solution is then added, after which the mea~ucement i8 made in the manner described with reference to Figs. 9-16.
ComParison between the results with the conventional miccoquick and Plasmaquick Pcocesses ln Fig. 17, the points indicate cesults obtained from a group of samples, on the one hand with a conventional ~`~ microquick process and on the other hand with a plasma-quick ecoces6. The Xl ~ measurements were obtained by the conventional microquick method, whereas the Yl %
mea6urements were obtained by the plasmaquick method.
In ocder to obtain comparable result6, the same reagent, e.g. CRB thromboplastin <ROCHE>, was used in both the conventional microquick method and in the plasmaquick method. In both methods the coagulation time was measured by the <COBAS> Fibro <ROCHE> device.
Fig. 17 shows the number n of samples tested, the regression equation in the form y = a ~ bx, and the ~-correlation coefficient r.
~ .
~': : : - :'.:; : : ~ ` . :: .:. :: :,-.:: : ~::: ::.:: :: : : : ': ,,: : : - ... . . : - :
2~2~
The microquick method acco~dinq to the invention In this method the blood sample is taken and processed as described with refe~ence to Pigs. 7 and 8. The coagulation time is measured with the <COBAS> Fibro device, in the same manner as described hereinbefore in the case of the conventional microquick process.
Comparison of results obtained accordinq to the invention with the microquick and the Plasmaquick Process In Fig. 18, point6 indicate results obtained from a group of samples, on the one hand by the microquick process according to the invention and on the other hand by a plasmaquick proces~. The X2 % measurements were obtained by the microquick process according to the invention, whereas the Y2 ~ measurements were obtained by the plasmaquick erocess. Two of the points measured in ~ -Fiq. 18 have identical X~ and Y2 values, and ~`~ consequently only eight points are shown for nine tested ~ samples in Fig. 18.
;~` To obtain comparable results, the same reagent, e.g.
, CR~ thromboplastin <ROCHE>, was used in both the micro-quick process according to the invention and in the plasmaquick erocess. In both methods the coagulation time was measured by the ~COBAS> Fibro <ROCHE> device.
Pig. 18 shows the number n of samples tested, the regression equation in the form y = a ~ bx and the correlation coefficient r.
As a compacison between Figs. 17 and 18 shows, the measurements obtained with the capillary tube according to ~- the invention or by the microquick process according to the invention are more closely correlated with the results obtained by the plasmaquick process, even in the region of relatively high values.
~ ' ' ' ` ` " ' i
The anticoagulant is preferably trisodium citrate at a concentration of 0.011 mol/l. Other suitable anti-coagulants are ethylene diamine tetraacetic acid di60dium salt (EDTA) or sodium fluoride. The substance used as an anticoagulant is placed in an aqueous ~olution, the 25 concentration being one-tenth of the corresponding concentration of venous blood 6ampling.
The excipients for the anticoagulant are preferably high~molecular additive6 such as fibrinogen`of bovines or 30 aqueous gelatine. Alternatively the excipient can e.g. by human fibrinogen, bovine albumin, polyethylene glycol PEG 8000 or polyvinyl pyrolidone 20 or 30. The excipients are used in the form of aqueous solutions, preferably at a concentration of 0.1 to 3.0%.
A capillary tube according to the invention as per Figs. 1-3 is preferably used in combination with a ., ..... : . : ........... .- : ... .~ : .... :, : . :: - :-, : :: ...... ::: .,: . " ., .. ~ .... . .
:, , - 2 ~ F~
matching test cell in a device for measuring the coagulation time of a blood sample. A measuring cell suitable for the purpose will now be described with reference ~o Figs. 4-6.
Fig. 4 is a plan view of a measuring cell 41 containing a capillary tube 81 according to the invention.
Fig. 5 shows a cross-section of the arrangement in Fig. 4 through line V-V in Fig. 4. Fig. 6 ~hows a cros6-section 10 of the aIransement in Fig. 4 through line VI-VI in Fig. 4.
The measuring cell 41 is made of material, e.g. a suitable plastic, for making optical, preferably photo-metric, measurements. Cell 41 need not necessarily have the shape shown in Figs. 4-6, but it is important for it to have a partition 44 having a sharp edge 43 at a distance from the bottom. ~he partition divides the top part of the cell into two compartments 7 and 8. As Fig. 6 shows, the top part of cell 41 has a holder 91 for 20 receiving a caeillary tube 81 according to the invention.
The capillary tube 81 i8 disposed in holder 91, preferably parallel to the longitudinal direction of cell 41, 60 that a part of the capillary tube projects from the cell.
Holder 91 is preferably constructed 60 that it can non-25 -positively connect the caeillary tube 81 to the cell 41.
Fig. 7 shows a blood sample 49 taken by a capillary tube al according to the invention and disposed in a measuring cell 41 as described. A patient's finger-tip i~
30 punctured with a lancet and a drop of blood flows out and is used for testing. The preset quantity of blood (10 to 50 microlitres) is drawn up through a capillary tube according to the invention, by holding the tube horizontal and keeping the tip in the droplet of ou~flowing blood.
~5 When sampled in this way, the blood is drawn into the capillary tube according to the invention, exclusively by the capillary force produced in the tube.
," . . ~ : , . - , . ' ' ' ~ . . ! : , ' . ' : . : ' ; . , ' , . ' ' , . . ' ': ' , , 202~ '3 As shown in Fig. 8, immediately after sampling the blood the end of the capillary 81 projecting from the cell 41 is closed by a cover 82. The cove~ is preferably made of a soft defo~mable material, e.g. bromobutyl rubber, and has a cavity 83 which contains a volume of air even after the cover has b2en placed on one end of the capillary tube.
The sample in the capillary tube 81 i6 transferred to the measuring cell 41 by a pressure surge produced by placing the cover on one end of the capillary tube. The sample is transfe~red mainly by gravity if the capillary tube is moved from the horizontal sampling position into a vertical position, when the sample flows from the capillary tube 81 and is received in the bottom part of the measu~ing cell 41. In orde~ to deliver all the sample from the capillary tube into the mea~uring cell 41, the ~op part of the cover 82 containing the cavity 83 is 20 pressed by the fingers. The resulting pressure surge ~.
ensures that the complete sample i8 transferred to the measuring cell. This is important for reproducing the measurements.
After the sample has been transferred to the measuring cell as aforementioned, the empty capillary tube. with or without a cover. can be le~t in the cell or removed theref~om, The measuring cell is then placed in a device for measuring the coagulation time. The construction and operation o$~this device will now be described with reference to Figs. 9 to 18. These drawings do not show the capillary tube according to the invention, because it is not necessary for the actual photometric measurement of the coagulation time.
Fig. 9 shows a measuring cell 1 inserted into the measuring device, and diagrammatically shows the electro--: ? ~
-optical arrangement of the measucing device. Cell 1 does not have the ame shape as cell 41 in Figs. 4-6, but basically has a very similar 6~ructure. Cell 1, like the cell 41 in Figs. 4-6, has a partition 2 which divides the top part of the cell into two compartments 7 and 8, and a sharp edge 3 at a distance from the base of the cell.
Fig. 9 shows an electro-optical arrangement comprising a light ~ource 5, e.g. a light-emitting diode, and a light receiver 6, e.g. a photodiode, in the arrangement shown.
These components produce and receive a light beam 4 which travels through the cell, ea6sing near and below the edge 3 in order to measure the extinction of the contents of the cell detected by light beam 4. The path of beam 4 is chosen so that the beam detects a clot 39 formed at edge 3.
The electro-optical arrangement also contains a light --source 62, e.g. a light-emitting diode 62, and a light receiver 63, e.g. a photodiode 63, in the arrangsment shown. These component produ~e and receive a light beam 61 which travels through the cell, passing above edge 3, in order to measure the extinction of the contents of the sell detected by light beam 61. The path of beam 61 is chosen so that it does not detect the maximum preset amount of sa~ple inteoduced into the cell, but so that after a reagent for measuring the coagulation has been added, the light beam 61 detect~ the mixture of sample and reagent, even at the minimum preset volume.
~ ' In order to reduce the influence of environmental light on the extinction measurements by light beams 4 and 61, the light receivers 6 and 63 are preferably photo-diodes with built-in infrared filter~ having a pass band of about 900 to about 100 nm and a minimum attenuation of about 9940 nm. By this means the sensitivity of the measurements to environmental incande~cent lamp illumination is reduced e.g. by about a factor of 5.
'.' ~" , : ' 2 ~ 2 ~j O ~ ~3 As Fig. 10 shows. the compartment 7 in the top part of cell 1 is connected through an opening 9 to an arrangement 21 for generating a variable air pres6ure acting on the contents of the cell. The pressure moves the mixture of sample and reagent in the device according to the invention in a manner described hereinafter with reference to Fig. ll ~3). As described hereinafter with reference to Figs. 15 and 16, the arrangement 21 can contain a pump element in the form e.g. of a vibrating diaphragm 22. The resulting air pressure travel~ through a duct 23 and opening 19 into cell 1. The cell has an opening 10 which remains open during operation.
lS As shown in Fig. 11, the following step6 are carried out when the cell according to the invention is u6ed to measure the coagulation time of a blood sample.
(1) The preset 6tarting volume of prepaced blood or plasma ~ample 31 is delivered from a capillary tube such as 81 in Fig. 8 and received in the bottom part of cell 1, where it is incubated. ~s shown in Fig. 11, the chosen amount of sample is preferably too small to reach the edge 3. 80 that air can flow freely between edge 3 and the surface of the sample. In this manner the air pressure generated by arrangement 21 cannot move the sample, and the sample remains motionless until the preset quantity of reagent has been introduced into the cell.
(2) The preset starting volume of reagent is introduced into the cell. The mixture of sample and reagent is chosen so that the surface thereof always lies above the edqe 3 and the light beam 61. The effects. as soon as the reagent has been introduced into the cell, are as follows:
: ::
202~r . .
(3) The mixeure 32 of sample and reagent is detected by the light beam 61. This time marks the beginning of the measurement of the coagulation time. This time i~
registered by known electronic 6ignal-proce~sing means. As a result of the air pre~cure produced by the aforementioned means shown in Fig. 10, the sample--reagent mixture now flow~ and moves in reciprocation between po6itions (a) and (b) shown in Fig. 11 (3). As a re6ult the sample is thoroughly mixed with the reagent and the mixture flows ~ound the sharp edge 3 of the cell.
(4) As a result of the movement of the liquid relative to -edge 3 as shown in (3), a clot 33 form~ at edge 3 at the instant of coagulation. Since this clot is detected by light beam 4, there i8 a sudden, marked change in the extinction measured by the beam. The time when coagulation occurs, i.e. the coagulation ~; 20 time, is unambiguously and accurately measured by de~ermining this chanqe. The determination i8 made and the values are displayed by known electronic signal- -erocessing and data display means.
As a variant of the last-described method, and provided the measurement is not adversely affected, the ; ~-sample can be made big enough for its surface to lie above ~-edge 3 even when the cell contains the sample only. In this case, before the reagent i~ added, the sample i8 30 ~ detect,ed by the lightl beam 4 and moved by the afore-mentioned air pressure, in the manner shown for the sample-reagent mixture in Fig. 11 (3).
Figs. 12 to 14 illustrate use of the cell 41 in Figs.
4-6 in a measuring device as per Figs. 9 and 10.
-~.
2 0 2 ~
As shown in Fig. 12, the cell 41 is supplied with a variable air pressure through a side opening 42, which is connected by a line 77 to the aic-pre6surizing arrangement.
Fig. 13 shows cell 41 where it contains the ~ample only. Fig. 14 shows 41 when it contain~ the mixture of sample and reagent. In Fig6. 13 and 14 the positions of light beam 4 and 61 are marked by small circles.
In Figs. 13 and 14, the cell 41 is used in the same manner as described with reference to Fig. 11.
Fig. 15 is a diagrammatic cross-section through a preferred embodiment of the arrangement 21 (in Fig. 10) for producing the variable air pres6ure. The arrangement is contained in a casing 71, in which a diaphragm 72 is disposed and has a laminated icon core 73. The diaphragm 72 is vibrated by an electromagnetic drive device containing a magnetic corA 74 and a magnetic coil 75 and supelied with a suitable a.c. As a result a variable air eressure is eroduced in casing 71 and is supplied through lines 77 and 78 to the two cells in the device accordinq to the invention.
~ '', Fig. 16 is a diagram of a typical time curve of the air pre~sure obtainable by the device shown in Fig. lS.
The air eressure varies between ~2 and -2 millibars, and varies approximately in the form of a sine curve 06cillatinq a frequency of 40 Hz.
On the basis of the measured results presented in Figs. 17 and 18 it will be demonstrated hereinafter that when the blood sample is taken and processed by a capillary tube according to the invention in a microquick 35 erocess for measuring the coagulation time, the correlation achieved with correseonding results from a ::
- ~21~3~
plasmaquick method, such results being recognized as accurate and reliable, i5 better than when the blood sample is taken and processed by the conventional method described in the opening part of this description.
It will be appreciated at this point that in the aforementioned processes there are considerable differences in the method of taking and processing the samQle for determining the coagulation time. This will be evident from the following description of these processes.
The Pla6maquick Process The plasmaquick process is a method of determining the lS thromboplastin time, using venous citrate plasma. In the conventional plasmaquick process, plasma is obtained by the following procedure:
U6ing a sterile plastic 2 ml throwaway syringe 20 containing exactly 2 ml of sterile 0.1 mol/l sodium citrate solution, blood is drawn from a vein puncture up ~ to the 2.0 ml mark, the plunger is retracted and the ; contents i8 quickly and completely mixed by repeatedly inclining the syringe. The citrate blood is centrifuged at 25 3000 rpm (about 1600 g) for 15 minutes.
: - :
The coagulation measurements should be made immediately if possible, but always within two hours after sampling the blood. The resulting plasma is kept in 30 throwaway plastic tubes at 15-25C.
The coagulation time is measured e.g. with the <COBA5>
Fibro device, the ba6ic construction and operation of which have already been described with reference to Figs.
35 9-16. A <COBAS> Fibro measuring cell, automatic micro- ~ -pipettes for volumes of 100 and 200 microlitres and a ' ' ' ' ' '' ~ : . .' . ~ : ., :. '~:: '. .: . . :'.: :, : . : :: , - `` 2 ~ 2 '3 ~
stop-watch ace also required ~or the meaæurement with <COBAS~ Fibco. Befoire making the measurement, a volume of 0.1 ml of the plasma obtained by the aforegoing procedure is pre-heated at 37C for 2 minute~, uæing a preheated cell and the <COBAS> Fibro unit heater. 0.2 ml of reagent solution is then added, after which the measurement iæ
made in the manner desccibed with reference to Figæ. 9-16.
The conventional microquick Proce6s The conventional microquick process is a method of determining the thromboplastin time using capillairy citrate blood. In the conventional microquick process, the blood æample is taken and prepared as follows before measuring the coagulation time:
:: :
1. Draw citrate solution into a capillary up to the 0.005 ml mark.
2. Clean finger (preferably middle or ring finger of left hand) with alcohol and prick with a lancet. Wash off the firæt dropæ of blood.
25 3 Pour blood up to the 0.050 ml mark into the capillary y~ containing citrate solution. Blow out immediately into a glaæs oc plastic tube or directly into the bottom of the mea~uring cell of a coagulation-time measuring device (avoid foaming) and mix by moving it in a circle. ~ , i~
4. Measure the coagulation within lO minutes if possible, but never later than 60 minutes after sampling the ;~ blood, and the citrate blood must never be left in the `~ 35 capillary, '~ ' ' : .
, ~:
The coagulation time is measured e.g. with a <COBAS~ -Fibro measuring device, the basic construction and operation of which have already been described with reference to Figs. 9-16. A <COBAS> Fibro measuring cell, an automatic micropipette for a volume of e.g. 50 microlitres and a stop-watch are required for making measurement6 with <COBAS> Fib~o. Before making the measurement, a volume of 0.050 ml of the capillary citrate blood obtained by the aforementioned procedure i~ pre--heated at 37C for 2 minutes u~ing the <COBAS> Fibro unit heateI. 0.050 ml of reagent solution is then added, after which the mea~ucement i8 made in the manner described with reference to Figs. 9-16.
ComParison between the results with the conventional miccoquick and Plasmaquick Pcocesses ln Fig. 17, the points indicate cesults obtained from a group of samples, on the one hand with a conventional ~`~ microquick process and on the other hand with a plasma-quick ecoces6. The Xl ~ measurements were obtained by the conventional microquick method, whereas the Yl %
mea6urements were obtained by the plasmaquick method.
In ocder to obtain comparable result6, the same reagent, e.g. CRB thromboplastin <ROCHE>, was used in both the conventional microquick method and in the plasmaquick method. In both methods the coagulation time was measured by the <COBAS> Fibro <ROCHE> device.
Fig. 17 shows the number n of samples tested, the regression equation in the form y = a ~ bx, and the ~-correlation coefficient r.
~ .
~': : : - :'.:; : : ~ ` . :: .:. :: :,-.:: : ~::: ::.:: :: : : : ': ,,: : : - ... . . : - :
2~2~
The microquick method acco~dinq to the invention In this method the blood sample is taken and processed as described with refe~ence to Pigs. 7 and 8. The coagulation time is measured with the <COBAS> Fibro device, in the same manner as described hereinbefore in the case of the conventional microquick process.
Comparison of results obtained accordinq to the invention with the microquick and the Plasmaquick Process In Fig. 18, point6 indicate results obtained from a group of samples, on the one hand by the microquick process according to the invention and on the other hand by a plasmaquick proces~. The X2 % measurements were obtained by the microquick process according to the invention, whereas the Y2 ~ measurements were obtained by the plasmaquick erocess. Two of the points measured in ~ -Fiq. 18 have identical X~ and Y2 values, and ~`~ consequently only eight points are shown for nine tested ~ samples in Fig. 18.
;~` To obtain comparable results, the same reagent, e.g.
, CR~ thromboplastin <ROCHE>, was used in both the micro-quick process according to the invention and in the plasmaquick erocess. In both methods the coagulation time was measured by the ~COBAS> Fibro <ROCHE> device.
Pig. 18 shows the number n of samples tested, the regression equation in the form y = a ~ bx and the correlation coefficient r.
As a compacison between Figs. 17 and 18 shows, the measurements obtained with the capillary tube according to ~- the invention or by the microquick process according to the invention are more closely correlated with the results obtained by the plasmaquick process, even in the region of relatively high values.
~ ' ' ' ` ` " ' i
Claims (5)
1. A capillary tube (11, 12, 13) for taking capillary blood samples for a system for measuring the coagulation time, which (a) is made of a plastic and (b) has a lyophilizate approximately uniformly distributed in its interior and over its entire length, the lyophilizate being obtained by freeze-drying a mixture containing an anticoagulant and at least one high--molecular additive.
2. A method of manufacturing a capillary tube according to claim 1, which method comprises (a) filling the entire interior of a plastic capillary tube with a liquid mixture containing an anti-coagulant and at least one high-molecular additive, and (b) freeze-drying the mixture in the interior of the capillary tube.
3. A device for measuring the coagulation time of a capillary blood sample, the device containing a cell (41) for photometric measurement of the coagulation time of a blood sample, the cell being made of plastic and its top part being divided by a partition (44) into two compart-ments (7, 8) and the partition having a sharp edge (43) at a distance from the base of the cell, wherein (a) the device contains a capillary tube (11, 12, 13, 81) according to the invention and a matching cover (82) for closing one end of the capillary tube, and (b) the top part of the cell (41) has a holder (91) for receiving the capillary tube and in which the capillary tube can be so disposed parallel to the longitudinal direction of the cell that a part of the capillary tube projects from the cell.
4. A device according to claim 3, wherein the holder (91) is so constructed that it can operatively connect the capillary tube (81) to the cell (41).
5. A device according to claim 3, wherein the cover (82) is made of a deformable material and has a cavity (83) which contains a volume of air even after the cover has been placed on one end of the capillary tube.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH3572/89 | 1989-10-02 | ||
| CH357289 | 1989-10-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2025055A1 true CA2025055A1 (en) | 1991-04-03 |
Family
ID=4258885
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002025055A Abandoned CA2025055A1 (en) | 1989-10-02 | 1990-09-11 | Capillary tube for taking blood samples |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0421175A1 (en) |
| JP (1) | JPH03121052A (en) |
| AU (1) | AU6365390A (en) |
| CA (1) | CA2025055A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE9417612U1 (en) * | 1994-11-03 | 1995-01-05 | Kloth Bernd | Sampling device |
| CA2446328C (en) * | 2002-10-29 | 2013-12-31 | Bayer Healthcare Llc | Optical reagent format for small sample volumes |
| JP4953441B2 (en) * | 2007-05-10 | 2012-06-13 | 国立大学法人京都工芸繊維大学 | Blood collection tool |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2076366A5 (en) * | 1970-01-13 | 1971-10-15 | Chemla Gilbert | |
| US3951606A (en) * | 1974-05-17 | 1976-04-20 | Geomet, Inc. | Apparatus for prothrombin testing |
| AT382971B (en) * | 1981-06-16 | 1987-05-11 | Hoffmann La Roche | METHOD AND DEVICE FOR MEASURING THE BLOOD CLUTTING TIME |
| US4873993A (en) * | 1986-07-22 | 1989-10-17 | Personal Diagnostics, Inc. | Cuvette |
-
1990
- 1990-09-11 CA CA002025055A patent/CA2025055A1/en not_active Abandoned
- 1990-09-15 EP EP90117794A patent/EP0421175A1/en not_active Withdrawn
- 1990-09-28 JP JP2260345A patent/JPH03121052A/en active Pending
- 1990-09-28 AU AU63653/90A patent/AU6365390A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JPH03121052A (en) | 1991-05-23 |
| EP0421175A1 (en) | 1991-04-10 |
| AU6365390A (en) | 1991-04-11 |
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| Date | Code | Title | Description |
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| FZDE | Dead |