WO2013045695A2 - Procédé pour distribuer un échantillon de fluide corporel dans un système d'analyse, seringue conçue pour utilisation dans celui-ci et kit comprenant une telle seringue - Google Patents

Procédé pour distribuer un échantillon de fluide corporel dans un système d'analyse, seringue conçue pour utilisation dans celui-ci et kit comprenant une telle seringue Download PDF

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Publication number
WO2013045695A2
WO2013045695A2 PCT/EP2012/069341 EP2012069341W WO2013045695A2 WO 2013045695 A2 WO2013045695 A2 WO 2013045695A2 EP 2012069341 W EP2012069341 W EP 2012069341W WO 2013045695 A2 WO2013045695 A2 WO 2013045695A2
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WO
WIPO (PCT)
Prior art keywords
syringe
blood
body fluid
barrel
serum
Prior art date
Application number
PCT/EP2012/069341
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English (en)
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WO2013045695A3 (fr
Inventor
Adam WARCHUSKI
Piotr Garstecki
Marcin Izydorzak
Pawel MICHALAK
Kamil PRUSAK
Original Assignee
Pz Cormay S.A.
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
Priority claimed from PL396492A external-priority patent/PL396492A1/pl
Application filed by Pz Cormay S.A. filed Critical Pz Cormay S.A.
Publication of WO2013045695A2 publication Critical patent/WO2013045695A2/fr
Publication of WO2013045695A3 publication Critical patent/WO2013045695A3/fr

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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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • 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
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150213—Venting means
    • 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
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150236—Pistons, i.e. cylindrical bodies that sit inside the syringe barrel, typically with an air tight seal, and slide in the barrel to create a vacuum or to expel blood
    • 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
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150259—Improved gripping, e.g. with high friction pattern or projections on the housing surface or an ergonometric shape
    • 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
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150305—Packages specially adapted for piercing devices or blood sampling devices
    • 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
    • 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
    • A61B5/150755—Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
    • 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
    • A61B5/150763—Details with identification means
    • A61B5/150786—Optical identification systems, e.g. bar codes, colour codes
    • 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
    • B01L3/5021—Test tubes specially adapted for centrifugation purposes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0803—Disc shape
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers

Definitions

  • the invention relates to a method for delivering a sample of body fluid, and in particular blood, to an analysing system.
  • the invention comprises also a syringe for drawing blood and delivering blood serum for biomedical tests, and a kit for delivering blood serum comprising such a syringe.
  • a blood sample is to be collected from a patient, followed by subsequent separation of the blood cells (hematocytes, hematocrit) from the plasma (serum), and finally appropriate biochemical tests are carried out on the serum samples.
  • Blood samples from patients are obtained using standard syringes with needles or -at present mostly - using special vacuum vessels (tubes), made of glass or plastic, with a tight stopper and a fitted element with needle.
  • the needle is inserted in a blood vessel and the tube, initially empty, is shortly filed with blood. Then, the tube is disconnected from the needle, which results in a blood containing tube tightly closed with the stopper. If necessary, another empty tube may be subsequently connected to the needle.
  • both elements described here are disposable to guarantee the necessary sterility.
  • the said tubes with needles are known, for instance, from publications: US 2010323437 Al , KR 20080025050 A, or JP 200018940 ⁇ A.
  • the tubes are a few centimetres long, and their typical volumes range from a few hundred microliters to a few mililiters. It is also possible to collect a drop of capillary blood from the finger to a capillary that is wetted by blood. In such a procedure, blood is collected to the capillary and fills a tube that is appropriately prepared and connected to the capillary; the capillary is disconnected after the blood collection is completed. Blood cells are separated from plasma mostly by centrifuging blood closed in a vessel (e.g., in a tube mentioned in the paragraph above) in a centrifuge. The centrifuging results in blood cells (hematocrit) precipitated at the bottom of the tube, with the plasma (serum) above them.
  • hematocrit blood cells precipitated at the bottom of the tube, with the plasma (serum) above them.
  • the tubes so prepared are placed essentially vertically in racks and analysed in biochemical analysers.
  • Biochemical analysers are advanced automated devices used for testing chemical composition of the blood serum. For instance, the method is used to determine the blood content of the following substances: glucose, lipids (e.g., cholesterol, triglycerides), enzymes or ions. With a set of needles and an appropriate mechanism, the analyser draws a serum sample from the tube and mixes it in a small cuvette with appropriately selected reagents, which allows - for instance by photometric analysis of products of a chemical reaction - to determine concentrations of substances of interest in the blood serum.
  • lipids e.g., cholesterol, triglycerides
  • enzymes or ions e.g., enzymes or ions.
  • the analyser draws a serum sample from the tube and mixes it in a small cuvette with appropriately selected reagents, which allows - for instance by photometric analysis of products of a chemical reaction - to determine concentrations of substances of interest in the blood serum.
  • biochemical analysers based on the above method and performing the test procedure described above are commercially available devices (e.g., ELITech Flexor XL systems), and are subject matter of numerous patent applications and patents (e.g., publications: JP 821 1072 A, JP 10132735 A, JP 201033924 A, US 20040185549 Al , US20050014274 Al , US 4808380, US 0102399, or US20070065945 Al ).
  • a separate group of analysers are systems utilising disposable discs (e.g. commercially available models Abaxis Piccolo® Xpress and Samsung IVD- A10A) containing chemical reagents that are necessary to carry out diagnostic reactions (the existing designs use freeze-dried reagents) and enabling the use of necessary biological material. These designs require that the biological material collected earlier from the patient is transferred using an external dispensing instrument (pipette). This element of the process not only increases the number of operations that are necessary to perform an analysis, but also elongates the time needed to perform the test. The number of analyses that may be performed using disc-based analysers is limited by availability of the reagents, performing correctly after the freeze-drying process.
  • the reagents are dispensed with the use of the centrifugal force to assure a uniform spreading out of biological material and solvent to places where the freeze-dried reagents are stored and the chemical reactions take place.
  • Essential limitations for the accuracy of measurements performed with the disc technology-based analysers are related to the reproducibility of producing small portions of freeze-dried reagents and the reproducibility of dispensing.
  • the purpose of the invention is to provide a method for acquiring the blood serum for biochemical assays, and subsequently delivering the serum to the analyser, with a minimum number of operations to be performed.
  • a method for delivering a sample of body fluid to an analysing system comprising the steps: a) collecting the body fluid in a reservoir of a storage element, b) centrifuging the body fluid in the reservoir of the storage element, is characterised in that subsequently c) the body fluid is pushed out from the reservoir of the storage element to the analysing system.
  • said body fluid is blood.
  • step b) the blood is separated into plasma and blood cells by centrifuging.
  • step b) the blood is separated into serum and hematocrit by centrifuging.
  • step c) the plasma or the serum are pushed out to the analysing system.
  • a microfluidic system is used as the storage element.
  • step c) the body fluid is pushed out from a chamber of the microfluidic system to the analysing system by pumping the liquid through the microfluidic system.
  • a liquid immiscible with the body fluid is used.
  • a syringe is used as the storage element.
  • step c) the body fluid is pushed out from the reservoir of the storage element to the analysing system by movement of the plunger, preferably moved by the operator's palm or by an appropriate mechanism.
  • the body fluid is pushed out from the reservoir of the syringe ⁇ o the analysing system by pumping the liquid by the syringe.
  • the invention relates also to a syringe comprising a barrel for blood, bounded by the lateral surface, having an outlet at the first end and closed with plunger at the second end, characterised in that the said lateral surface of the barrel contains a hole, whereas the distance between the hole and the second end of the barrel is less than the length of the plunger, which allows for complete covering of the hole with the plunger by pressing the plunger into the barrel.
  • the internal lateral surface of the barrel forms a capillary tube with internal diameter from 0.2 mm to 4 mm, preferably from 1 mm to 2mm.
  • the internal surfaces of the barrel, the hole or the ferrule are coated with a substance accelerating blood clotting, selected from the group comprising: silica, colloidal silica, kaolin, glass particles, diatomaceous earth, thrombin based-agents, or ellagic acid.
  • a substance accelerating blood clotting selected from the group comprising: silica, colloidal silica, kaolin, glass particles, diatomaceous earth, thrombin based-agents, or ellagic acid.
  • the internal surfaces of the barrel, the hole or the ferrule are coated with a substance preventing blood clotting, selected from the group comprising: EDTA (salt of the ethylenediaminetetraacetic acid), trisodium citrate, heparinates (sodium, lithium, ammonium salt of heparin), hirudin, potassium oxalate, sodium fluoride, iodoacetate or thrombin inhibitors (e.g., PPACK or agratroban).
  • EDTA salt of the ethylenediaminetetraacetic acid
  • trisodium citrate trisodium citrate
  • heparinates sodium, lithium, ammonium salt of heparin
  • hirudin potassium oxalate
  • sodium fluoride iodoacetate or thrombin inhibitors (e.g., PPACK or agratroban).
  • the capillary terminal (4) is non-wettable by serum.
  • the invention relates also to a kit for delivering blood serum, comprising such a syringe, a microfluidic nozzle fitted to the outlet of the syringe barrel, and a centrifuge rotor, having a well used for placing the syringe therein together with installed nozzle, said well being adapted to the size and the form of the syringe with the nozzle.
  • a centrifuge rotor has a hole, through which the syringe plunger can be pushed in while the syringe is placed in the rotor well.
  • the centrifuge rotor has a hole at the place the syringe outlet is located, to allow for transferring serum from the syringe to the analyser.
  • the syringe comprising a barrel for blood, bounded by the lateral surface, having an outlet at the first end and closed with plunger at the second end, is characterised in that the said lateral surface contains a hole, whereas the distance between the hole and the second end of the barrel is less than the length of the plunger, which allows for complete covering of the hole with the plunger by pressing the plunger into the barrel.
  • the length of the plunger is such that after pressing the plunger entirely into the barrel the end of the plunger faces the end of the syringe.
  • the outlet is fitted with a capillary terminal.
  • the internal lateral surface of the barrel forms a capillary tube with internal diameter from 0.2 mm to 4 mm, preferably from 1 mm to 2 mm.
  • the length of the barrel is from 10 mm to 200 mm, more preferably from 30 mm do 70 mm.
  • the hole is round, with diameter from 0.2 mm do 4 mm, preferably from 1 mm do 2 mm.
  • the hole has a ferrule in the form of a funnel for easy blood drawing.
  • the capacity of the syringe barrel is from 20 to 1000 mm 3 , more preferably from 25 to 250 mm 3 , and most preferably from 50 to 150 mm 3 .
  • internal surfaces of the barrel, the hole or the ferrule are coated with a substance accelerating blood clotting, selected from the group comprising: silica, colloidal silica, kaolin, glass particles, diatomaceous earth, thrombin based-agents, or ellagic acid.
  • a substance accelerating blood clotting selected from the group comprising: silica, colloidal silica, kaolin, glass particles, diatomaceous earth, thrombin based-agents, or ellagic acid.
  • internal surfaces of the barrel, the hole or the ferrule are coated with a substance preventing blood clotting, selected from the group comprising : EDTA (sa lt of the ethylenediaminetetraacetic acid), trisodium citrate, heparinates (sodium, lithium, ammonium salt of heparin), hirudin, potassium oxalate, sodium fluoride, iodoacetate or thrombin inhibitors (e.g., PPACK or agratroban).
  • EDTA sa lt of the ethylenediaminetetraacetic acid
  • trisodium citrate trisodium citrate
  • heparinates sodium, lithium, ammonium salt of heparin
  • hirudin potassium oxalate
  • sodium fluoride iodoacetate or thrombin inhibitors
  • the capillary terminal is non-wettable by serum.
  • the syringe has a holder placed along the side wall of the barrel and connected therewith.
  • the syringe has tabs for finger support near the second end of the barrel.
  • the invention comprises also a kit for delivering blood serum, comprising the above syringe, a microfluidic nozzle fitted to the outlet of the syringe barrel, and a centrifuge rotor, having a well used for placing the syringe therein together with installed nozzle, said well being adapted to the size and the form of the syringe with the nozzle.
  • the centrifuge rotor has a hole, through which the syringe plunger can be pushed in while the syringe is placed in the rotor well.
  • the centrifuge rotor has a hole at the place the syringe outlet is located, to allow for transferring serum from the syringe to the analyser.
  • microfluidic system comprises any system containing a cha nnel with at least one characteristic dimension (e .g ., dia meter) not greater tha n 2 m m .
  • the microfluidic system may be preferably fabricated from a polymer, e.g., polycarbonate, polypropylene, polyethylene, polystyrene or another polymer suitable for injection moulding. Layered systems are particularly preferable here, especially those having holes in the u pper layer, a nd microfluidic channel or channels in the lower layer.
  • Fig. 1 shows schematically an empty syringe according to the invention in a preferred embodiment, connected to a nozzle
  • Fig. 2 shows schematically a fragment of a blood-filled syringe from Fig.
  • Fig. 3 shows schematically a blood-filled syringe from Fig. 1 , placed in a centrifuge rotor according to the invention
  • Fig. 4 illustrates schematically delivering the serum to the analyser from the syringe according to the invention through a nozzle
  • Fig. 5 presents schematically a microfluidic system (chip) according to the invention in a preferred embodiment
  • Fig. 6 presents schematically the microfluidic system from Fig. 5, filled with a blood sample in a preferred embodiment
  • Fig. 7 presents schematically the microfluidic system from Fig. 6, placed in a centrifuge rotor according to the invention, and
  • Fig. 8 illustrates schematically the microfluidic system from Fig. 6 after completed centrifugation and separation of morphotic blood elements from the serum.
  • the following labelling is used in the drawings: 1 - barrel 2 - hole, 3 - plunger, 4 - capillary terminal, 5 - microfluidic nozzle, 6 - tube delivering the serum to the junction, 7 - sensor, 8 - outlet port, 9 - microfluidic nozzle socket, 10 - blood, 1 1 - axis of rotation, 12 - well, 13 - hole, 14 - rod, 15 - serum, 1 6 - droplet, 1 7 - hematocrit, 21 - venting hole/hole used for delivering the fluid pushing the serum (or plasma) out from the barrel, 22 - venting hole/hole used for delivering the serum (or plasma) to the analyser, 23 - hole for blood drawing, 24 - barrel, 25, 26, 27 - channels connecting respective holes with the barrel.
  • Example 1 delivering the sample using a syringe - the syringe 1
  • a syringe is fabricated, wherein the barrel 1 for blood is made of a polystyrene tube (external diameter 3 mm, internal diameter 2 mm, length 70 mm) .
  • the barrel 1 for blood is made of a polystyrene tube (external diameter 3 mm, internal diameter 2 mm, length 70 mm) .
  • the hole 2 In the side wall of the tube there is a hole 2 with a diameter of 2 mm, whereas the centre of the hole 2 is located 4 mm from the end of the tube, which is used to insert the plunger 3.
  • the hole 2 may have a ferrule in the form of a funnel for easy blood drawing into the syringe.
  • the syringe is fitted with a plunger 3 with the following dimensions: external diameter (at the place the connection with the tubing is sealed) - 2.05 mm, external diameter (on the remaining length) - 1 .98 mm, length - 8 mm.
  • the plunger 3 is made of Dyneon (it is possible to fabricate the plunger 3 from other polymers, for example and non-limiting, polyvinyl chloride PVC, polypropylene PP, Teflon, Dyneon, rubbers consisting of natural, isoprene or nitrile rubbers, or possibly of a hard core-soft shell composite - sealing; besides, most typical polymers may be used.
  • the capacity of the syringe in the embodiment presented here is 200 ⁇ _.
  • a holder (not shown in the drawing) - the holder (e.g., in the form of a rectangle) may be located along the tube that is the body of the syringe and be connected with the body. It may also be created in the form of a flat 'fin' attached to the syringe body. Such a holder may be also used for labelling the sample to be collected (e.g., with a bar code label).
  • the tube 1 , the hole 2 and the ferrule (not shown in the drawing) may contain on their internal surfaces substances deposited by evaporation that are desirable with regard to the final result of the blood separation.
  • EDTA salt of the ethylenediaminetetraacetic acid
  • trisodium citrate trisodium citrate
  • heparinates sodium, lithium, ammonium salt of heparin
  • hirudin potassium oxalate
  • sodium fluoride iodoacetate
  • thrombin inhibitors e.g., PPACK or agratroban
  • silica silica, kaolin, glass particles, diatomaceous earth, thrombin based-agents, or ellagic acid.
  • the syringe according to the invention may have a finger support at the plunger 3.
  • the syringe according to the invention may have in the barrel 1 an additional inlet at the place the blood 10 is located, and preferably at the place the serum (plasma) 15 is located after centrifuging and separation.
  • an inlet is not shown in the drawing. This inlet allows for delivering (after centrifuging and separation) a fluid immiscible with the serum (plasma) 15 (e.g., oil) and pushing out a desired serum (plasma) 15 portion from the barrel 1 using an applied flow of this immiscible fluid.
  • the syringe - according to the invention - is used as follows:
  • the blood 10 is aspired to the syringe spontaneously, due to capillary forces.
  • an adult fills it within about 30 seconds, whereas the amount of blood collected and sufficient for blood testing is only 0.2 ml, i.e., about ten times less than for traditional syringes or blood collection tubes mentioned in the introduction.
  • the plunger 3 is pressed in to the depth of 8 mm (so that it entirely fits in the tube) - resulting in the hole 2 in the side wall being closed by the plunger 3.
  • the plunger 3 is designed so as to be able to be pushed to the end of the barrel 1 with no risk to be pushed in too deeply.
  • the syringe has a capillary terminal 4, allowing to connect the syringe outlet with a microfluidic nozzle 5, fitted with a serum sensor 7 (optical or electrical) and terminated with the outlet 8.
  • the nozzle 5 contains a socket 9, allowing to insert the terminal 4.
  • the syringe is placed in the centrifuge rotor so that the outlet 8 of the microfluidic nozzle 5 points towards the axis of rotation 1 1 , and the plunger 3 points outwards from the axis of rotation 1 1 , and during centrifuging prevents the collected material 10 from flowing out.
  • the centrifuge rotor has a well 12 adapted to the size and the form of the syringe.
  • the rotor is made of aluminium (or other suitable material - for instance ABS, polyacetal (POM), polystyrene or polyamide 66 with a fiber glass filler).
  • the blood 10 is separated into the serum 15 and the hematocrit 17, whereas the serum 15 is positioned closer to the axis of rotation 1 1 and the syringe outlet, and the hematocrit 17 - further from the axis of rotation 1 1 and the syringe outlet.
  • the rotor has holes 13, allowing to insert from outside a rod 14 pressing the plunger 3, in order to initiate the flow of the separated serum 15 and deliver it for further processing, e.g., to an analysing system (not shown in the drawing).
  • the serum 15 flows out through additional holes in the rotor (positioned closer to its centre).
  • the rotor contains additionally a hole at the place the end of the syringe is located (closer to the axis of rotation 1 1 ).
  • centrifuging must be carried out by setting appropriate time and rotational speed.
  • the parameters of centrifugation - time and rotational speed e.g., 15 minutes at 3000 rpm, or 2 minutes at 8000 rpm - are known to those skilled in the diagnostic testing.
  • the plunger 3 may be pressed into the tube 1 , which results in pushing out the serum 15 from the syringe and transferring it through the microfluidic nozzle 4 to the analysing system (not shown in the drawing).
  • Example 2 delivering the sample using a syringe with conventional plunger
  • the centrifuging is carried out according to parameters given below.
  • serum or plasma located closer to the syringe outlet
  • hematocrit located closer to the plunger
  • Example 3 delivering the sample using a microfluidic system (chip)
  • a two-layered microfluidic chip has been fabricated, wherein the lower layer consists of channels and a chamber for the blood sample.
  • the upper plate has three holes including the hole 23 allowing to apply the blood sample directly from the patient' s finger.
  • the hole 23 can be adapted for installation of capillaries or a funnel for easy blood collection.
  • the hole 22 used for delivering serum (or plasma) to an analyser can be optionally adapted for installation of capillaries for easy transfer of the fluid.
  • each hole (21 , 22, or 23) may be used for blood sample collection, and additionally each hole can be placed both in the upper and in the lower plate, and on the external edge resulting from joining the plates.
  • the hole 21 with the channel 25 are used after the centrifugation is completed, to push out the serum (or plasma) obtained, and that the hole 22 with the channel 26 are used for delivering the serum to the analyser - during this operation the hole 23 must be closed.
  • the inlet of the channel 25 to the chamber 24 should take into account the biological variability of the material being collected so that after separation the blood cells are below that inlet. Both layers of the system have been durably joined so as to maintain the necessary tightness of the entire microfluidic system.
  • the capacity of the entire microfluidic system in the embodiment discussed here is about 150 ⁇ _, and the width of the channels inside the chip (25, 20, and 27) is 1 mm.
  • the chip's internal channels may contain on their surfaces substances deposited by evaporation that are desirable with regard to the final result of the blood separation. These substa nces may be used to prevent blood coagulation, for exa m ple a nd non-limiting including: EDTA (salt of the ethylenediaminetetraacetic acid), trisodium citrate, heparinates (sodium, lithium, ammonium salt of heparin), hirudin, potassium oxalate, sodium fluoride, iodoacefafe or thrombin inhibitors (e.g., PPACK or agratroban). These substances may also be used to activate blood coagulation, for example and non-limiting including: silica, kaolin, glass particles, diatomaceous earth, thrombin based-agents, or ellagic acid.
  • EDTA salt of the ethylenediaminetetraacetic acid
  • trisodium citrate trisodium citrate
  • microfluidic system - according to the invention - is used as follows:
  • the patient puts pricked finger to the hole on the chip surface.
  • the blood is aspired to the system spontaneously, due to capillary forces.
  • an adult fills it within about 30 seconds, whereas the amount of blood collected with this method and sufficient for blood testing is only 0.15 cm 3 , i.e., about ten times less than for traditional syringes or blood collection tubes mentioned in the introduction.
  • After filling the chip with blood it is placed in a specially prepared rotor (Fig. 3).
  • the centrifuge rotor has a well adapted to the size and the form of the system.
  • the rotor is made of aluminium (or other suitable material - for example ABS, polyacetal (POM), polystyrene or polyamide 66 with a fiber glass filler) .
  • the blood is separated into the plasma (or serum) and the hematocrit, whereas the plasma is positioned closer to the axis of rotation in the microfluidic chamber, and the hematocrit - further from the axis of rotation.
  • the rotor and the chip have holes, allowing to deliver oil through a hydraulic system, whereas said oil is used to dispense the plasma in portions to an analysing system (not shown in the drawing) .
  • By pumping oil to the microfluidic system a portion of plasma is pushed out from the system. The plasma flows out through a hole in the rotor.
  • centrifugation must be carried out by setting appropriate time and rotational speed.
  • the parameters of centrifugation - time and rotational speed, e.g., 3 minutes at 8000 rpm - are known to those skilled in the diagnostic testing.

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  • Manufacturing & Machinery (AREA)
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  • Dispersion Chemistry (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention concerne un procédé pour distribuer un échantillon de fluide corporel dans un système d'analyse, comprenant les étapes consistant à : a) collecter le fluide corporel dans un réservoir d'un élément de stockage, b) centrifuger le fluide corporel dans le réservoir de l'élément de stockage, caractérisé en ce qu'ensuite c) le fluide corporel est poussé depuis le réservoir (4, 24) de l'élément de stockage vers le système d'analyse. L'invention comprend en outre une seringue prévue pour utilisation dans un tel procédé pour distribuer un échantillon de fluide corporel vers un système d'analyse et un kit pour distribuer du sérum sanguin comprenant une telle seringue.
PCT/EP2012/069341 2011-09-30 2012-10-01 Procédé pour distribuer un échantillon de fluide corporel dans un système d'analyse, seringue conçue pour utilisation dans celui-ci et kit comprenant une telle seringue WO2013045695A2 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
PL396492A PL396492A1 (pl) 2011-09-30 2011-09-30 Strzykawka, zestaw do dostarczania surowicy krwi zawierajacy taka strzykawke oraz sposób dostarczania surowicy krw, wykorzystujacy taka strzykawke
PLP-396492 2011-09-30
PL399243A PL399243A1 (pl) 2011-09-30 2012-05-18 Sposób dostarczania próbki plynu ustrojowego do ukladu analizujacego
PLP-399242 2012-05-18
PL399242A PL399242A1 (pl) 2011-09-30 2012-05-18 Sposób dostarczania próbki plynu ustrojowego do ukladu analizujacego
PLP-399243 2012-05-18

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WO2013045695A3 WO2013045695A3 (fr) 2013-08-22

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WO2014049116A1 (fr) 2012-09-27 2014-04-03 Pz Cormay S.A. Système microfluidique et procédé pour la distribution d'un échantillon d'un fluide corporel à un système d'analyse en utilisant le système microfluidique
WO2015140740A1 (fr) * 2014-03-21 2015-09-24 Dbs System Sàrl Dispositif et méthode de séparation d'un fluide complexe comme le sang
WO2018178895A1 (fr) * 2017-03-31 2018-10-04 Pz Cormay S.A. Système microfluidique
US10335784B2 (en) 2012-03-31 2019-07-02 Dbs System Sa Device and method for dried fluid spot analysis
WO2019146734A1 (fr) * 2018-01-25 2019-08-01 国立大学法人山梨大学 Appareil de séparation , procédé de séparation, dispositif de séparation, appareil d'inspection et procédé d'inspection

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JPH10132735A (ja) 1996-10-28 1998-05-22 Hitachi Ltd 自動分析装置
US6162399A (en) 1997-07-30 2000-12-19 Grupo Grifols, S.A. Universal apparatus for clinical analysis
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10335784B2 (en) 2012-03-31 2019-07-02 Dbs System Sa Device and method for dried fluid spot analysis
WO2014049116A1 (fr) 2012-09-27 2014-04-03 Pz Cormay S.A. Système microfluidique et procédé pour la distribution d'un échantillon d'un fluide corporel à un système d'analyse en utilisant le système microfluidique
WO2015140740A1 (fr) * 2014-03-21 2015-09-24 Dbs System Sàrl Dispositif et méthode de séparation d'un fluide complexe comme le sang
US10670579B2 (en) 2014-03-21 2020-06-02 Dbs System Sa Device and method for separating a fluid mixture such as blood
WO2018178895A1 (fr) * 2017-03-31 2018-10-04 Pz Cormay S.A. Système microfluidique
WO2019146734A1 (fr) * 2018-01-25 2019-08-01 国立大学法人山梨大学 Appareil de séparation , procédé de séparation, dispositif de séparation, appareil d'inspection et procédé d'inspection
JPWO2019146734A1 (ja) * 2018-01-25 2021-02-25 国立大学法人山梨大学 分離装置及び分離方法、分離デバイス、並びに検査装置及び検査方法
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JP7163558B2 (ja) 2018-01-25 2022-11-01 国立大学法人山梨大学 分離装置及び分離方法、分離デバイス、並びに検査装置及び検査方法

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