WO2005082251A1 - Collection of a specimen - Google Patents

Collection of a specimen Download PDF

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Publication number
WO2005082251A1
WO2005082251A1 PCT/SE2005/000243 SE2005000243W WO2005082251A1 WO 2005082251 A1 WO2005082251 A1 WO 2005082251A1 SE 2005000243 W SE2005000243 W SE 2005000243W WO 2005082251 A1 WO2005082251 A1 WO 2005082251A1
Authority
WO
WIPO (PCT)
Prior art keywords
specimen
solution
sample
test
taking
Prior art date
Application number
PCT/SE2005/000243
Other languages
French (fr)
Inventor
Hans-Axel Hansson
Original Assignee
Datainnovation I Lund Ab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Datainnovation I Lund Ab filed Critical Datainnovation I Lund Ab
Publication of WO2005082251A1 publication Critical patent/WO2005082251A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/155Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150015Source of blood
    • A61B5/150022Source of blood for capillary blood or interstitial fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150015Source of blood
    • A61B5/15003Source of blood for venous or arterial blood
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150053Details for enhanced collection of blood or interstitial fluid at the sample site, e.g. by applying compression, heat, vibration, ultrasound, suction or vacuum to tissue; for reduction of pain or discomfort; Skin piercing elements, e.g. blades, needles, lancets or canulas, with adjustable piercing speed
    • A61B5/150061Means for enhancing collection
    • A61B5/150099Means for enhancing collection by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150206Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150221Valves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150206Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150229Pumps for assisting the blood sampling
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150206Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150274Manufacture or production processes or steps for blood sampling devices
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150755Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150763Details with identification means
    • A61B5/150793Electrical or magnetic identification means
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150007Details
    • A61B5/150847Communication to or from blood sampling device
    • A61B5/150862Communication to or from blood sampling device intermediate range, e.g. within room or building
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/150992Blood sampling from a fluid line external to a patient, such as a catheter line, combined with an infusion line; blood sampling from indwelling needle sets, e.g. sealable ports, luer couplings, valves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/151Devices specially adapted for taking samples of capillary blood, e.g. by lancets, needles or blades
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/15Devices for taking samples of blood
    • A61B5/153Devices specially adapted for taking samples of venous or arterial blood, e.g. with syringes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00Evaluating a particular growth phase or type of persons or animals
    • A61B2503/40Animals

Definitions

  • the present invention relates generally to automatic collection of a specimen from a subject of an experiment, such as a living being. More specifically, the invention relates to automatic collection of a specimen having a minimised influence on the normal behaviour and movement of the living being.
  • sample taking systems or devices is not portable and comprises often sample taking components, such as valves, pumps and test tubes, arranged at a distance from the laboratory animal.
  • sample taking components such as valves, pumps and test tubes
  • the distance between the laboratory animal and the sample taking components requires that the tubings or the like connected between the laboratory animal and the sample taking components have to be quite long to provide free movement of the animal.
  • the long tubings often require that the volume of a taken specimen has to be quite large due to the long distance the taken sample has to be transported in the tubings.
  • the volume of the taken specimen or sample need to be very small, and especially when the specimen is taken from small laboratory animals.
  • the volume of the taken sample is usually in the range of 25 - 250 microlitres or 100 - 500 microlitres, respectively. Further, when taking a bile sample from a rat the volume is usually in the range of 100 - 500 microlitres depending on for example the time period for the sampling or the kind of study.
  • a problem to be solved is to provide sample taking on a freely moving laboratory animal in order to minimise the effect of the sample taking procedure on the animal.
  • Another problem to be solved is to provide taking of samples having a small volume.
  • a problem to be solved in embodiments of the invention is to control the rate of a supplied solution through a test site of a subj ect of an experiment. Another problem to be solved is to avoid air bubbles in the taken specimen comprised in the test tube. Yet another problem to be solved is to minimise the risk of contaminating the outer surface of the means, e.g. a hollow needle, delivering the sample to the test tube, which contamination occurs if the outer surface of the needle during the delivery of the sample is in contact with a part of the sample already delivered to the test tube. It is critical to avoid such a contamination of the outer surface of the hollow needle since in the case of taking multiple samples, which are dispensed to different test tubes, the contamination of the outer surface of the needle will also contaminate the subsequent samples.
  • the means e.g. a hollow needle
  • the overall object of the present invention is to solve among others the above mentioned problems of automatically collecting a specimen from a subject of an experiment, i.e. from a living test object, with a minimised influence on the normal behaviour and movement of the test obj ect. More specifically embodiments of the present invention provides a portable sample taking device providing taking of a sample having a small volume, and seeks to control the taking of a specimen to receive a specimen of hig quality and a specimen that is representative for the fluid or solution from which the specimen is taken, to reduce the power consumption, to avoid air bubbles in a taken specimen and/or to minimise unintentional contamination of a taken specimen.
  • a further aspect of the invention is directed to a computer program product for use in a data processing system and devised for controlling automatic specimen taking in accordance with the inventive method.
  • the computer program product comprises computer program code portions, possibly stored on a storage medium and devised to control the data processing system to control the specimen taking apparatus to perform the steps of the inventive method.
  • distal and the proximal parts of a component refer to the parts of the component that are farthest from and closest to a subject of an experiment, respectively.
  • Fig. la schematically shows an embodiment of a specimen taking system according to the present invention
  • Fig. lb schematically shows an embodiment of a specimen taking device according to the present invention attached to a laboratory animal
  • Fig. 2a schematically shows a first embodiment of a specimen taking device according to the present invention
  • Fig. 2b schematically shows a second embodiment of a specimen taking device according to the present invention
  • Fig. 2c schematically shows a third embodiment of a specimen taking device according to the present invention.
  • Fig. 2d schematically shows a fourth embodiment of a specimen taking device according to the present invention
  • Fig. 2e schematically shows a fifth embodiment of a specimen taking device according to the present invention
  • Fig. 2f schematically shows a sixth embodiment of a specimen taking device according to the present invention
  • FIG. 3 schematically shows an embodiment of a specimen taking device configured to take blood sample according to the present invention
  • Fig. 4 shows a flow chart of method steps for taking a blood sample
  • Fig. 5 shows another flow chart of method steps for taking a blood sample
  • Fig. 6a-6i schematically show the contents in a sample collector at different steps during the method described in conjunction with Fig. 5;
  • Fig. 7a schematically shows a side view of components of a specimen taking device according to the present invention
  • Fig. 7b shows schematically a perspective view of components of a specimen taking device according to the present invention
  • Fig. 7c shows schematically another side view of components of a specimen taking device according to the present invention
  • Fig. 7d shows schematically a view of components of a specimen taking device according to the present invention taken from the fraction assembler
  • Fig. 7e shows schematically a view of a housing according to the invention.
  • Fig. 8a and 8b schematically shows a perspective view and a top view, respectively, of a fraction assembler according to the invention
  • the present invention refers to automatic collection of a specimen from a subject of an experiment, such as a living being. More specifically the invention refers to automatic collection of a specimen entailing a minimised influence on the normal behaviour and movement of the living being.
  • the described embodiments of the invention are directed to collecting, sampling or taking liquid specimen from for example a vessel or a tissue structure in a subject of an experiment or from some other kind of structure containing a fluid or a liquid substance.
  • embodiments of the invention are used for taking samples of urine, bile, or blood.
  • the apparatus according to the invention may be adapted to collect solid material samples from a test object.
  • the subject of an experiment is in most cases a living being, such as a laboratory animal.
  • different laboratory animals are used, but rats, mice, dogs and pigs are among the most frequently used laboratory animals.
  • Exemplifying embodiments of the invention will be described below with reference to the accompanying drawings in which the laboratory animal is a pig or a dog, but it should be understood that the laboratory animal can be another kind of animal and that a described embodiment is not restricted to apply only to the animal shown in the figure referred to in the description text.
  • the subject of an experiment can also refer to another subject or test object that is exposed to repetitive taking of samples, such as a container comprising a liquid, consistent or solid test material.
  • a container comprising a liquid, consistent or solid test material.
  • the specimen taking system 10 comprises one or several specimen taking apparatuses or sample taking devices 100 each, of which is portable and removably attached to a subject of an experiment, for example a laboratory animal.
  • the sample taking device 100 can be removably attached around the neck of the laboratory animal 1 by means of a necklace 101 having a Velcro ® fastening or snap locking.
  • the sample taking device 100 can of course be removably attached to another body part or in another way, but the sample taking device 100 is preferably attached to the subject of the experiment in such a way that the normal behaviour or movement of the living being is not disturbed.
  • the sample taking system 10 comprises further one or several computerised units
  • the sample taking device comprises means for taking and storing one or several specimens, a communication interface, a micro processor, a storing means and electronics.
  • Embodiments of the sample taking device can further comprise a solution source and means for supplying a solution from the solution source to a test object.
  • the sample taking device can comprise a gas source and means for supplying gas from the gas source. Further, the sample taking device comprises a power source, such as a battery, arranged to provide power to components of the sample taking device.
  • the battery can be rechargeable.
  • Embodiments of the personal computer 102 can comprise means for inputting data or information, user interface, communication interface, means for storing information concerning for example information relating to a laboratory animal and test schemes, i.e. information relating to the laboratory animal, when to take a specimen, the time interval between consecutive specimens, the volume of the specimen to be taken, the number of specimen to be taken, etc.
  • the information can for example be stored in a database 103 communicatively connected to the computerised unit 102.
  • the computerised unit 102, 104 can be arranged to control the taking of one or several specimens.
  • the computerised unit 102, 104 can be arranged to start, stop or pause the taking of specimen.
  • the computerised unit 102, 104 can be arranged to read information relating to the study from the sample taking device.
  • the information stored in the computerised unit 102, 104 which relates to a study of a specific laboratory animal can be transmitted from the computerised unit 102, 104 to a sample taking device 100 of the specific laboratory animal.
  • the sample taking device 100 comprises means for receiving and storing the information, e.g. test schemes, means for taking and storing specimens, and means for controlling the taking of the samples according to a test scheme.
  • the sample taking device 100 can be arranged to store information relating to the taken sample, e.g. the point of time when the sample was taken and the volume of the sample, in a storage means which can be comprised in the sample taking device.
  • the sample taking system 10 further comprises another computerised unit 105, which in this description text is called an office computer 105.
  • the office computer 105 is communicatively connected to the computerised unit 102, also called the laboratory computer 102, by means of a communication link 107.
  • the communication link 107 can for example be realised as a wired communication link, such as a network connection, or a wireless communication link using for example IR technique or bluetooth technique.
  • the office computer 105 is arranged to access information about a study, e.g. an ongoing study or a completed study, via the laboratory computer 102.
  • Each of the sample taking devices 100 has preferably a unique identity, e.g. an identification number or name, whereby an experimenter by means of the coinputerised unit 102 or a PDA 104 can establish a communication link with a specific sample taking device 100 and thus retrieve status information about the experiment.
  • the experimenter can for example retrieve information about how many samples that have been taken, when they have been taken, the volume of each of the taken samples and how many samples that are left to be taken.
  • the specimen taking system 10 and its functions are automatically controlled by means of computer program software being executed on a control data processing system.
  • the control data processing system may be a dedicated control data processor, a computerised unit 102, 104 or a sample taking device 100 set up with a suitable control program.
  • the user can through a user interface define the specimen taking procedure and different specimen taking parameters, for example by defining a selectable number of specimens to be taken with a selectable time interval or at specific points in time.
  • the computer program product comprises program code portions adapted to direct a data processing system to perform the steps of the inventive method or control the movements of the system components as described in this description.
  • the computer program product preferably comprises a carrier in the shape of a storage medium, such as a diskette or CD or the like, for storing the inventive computer program portions.
  • the components of the specimen talcing device and the laboratory animal are for the sake of clarity drawn apart from each other, but as mentioned above, the components of the specimen taking device is preferably arranged as an integrated unit which is portable, i.e. the integrated unit can easily be carrie by the test object, and removably attached to the test object.
  • a schematic first embodiment of a specimen taking device or sample taking device will now be described with reference to Fig.2a.
  • the embodiment of the specimen taking apparatus in accordance with the invention comprises a hollow specimen collector 120 comprising a proximal end 122 with an inlet and configured to be connectable to an outlet 132 of a test site or a test location 130 of a test object 1 and a distal end 124 having an outlet, whereby a taken sample from the test site 130 can be transported from the inlet of the proximal end 122 to the outlet of the distal end 124 through the specimen collector 120.
  • a sample can then by means of the natural flow rate at the outlet of the test site 130 be transported from the outlet 132 of the test site 130 through the specimen collector 120 and discharged to a test tube 140.
  • the proximal end of the specimen collector is preferably introduced into the urethra or the bile duct of the test object, respectively.
  • the samples can be taken at predetermined time points at an outlet from the test site using the natural rate of the outflow.
  • the samples can be taken at time points defined by a constant time interval, which can entail that the volume of the taken samples fluctuates between the samples.
  • a pressure sensor can be arranged at the outlet of the test site and arranged to measure the pressure at the outlet. The sensor can be connected to a control unit arranged to control the sample taking.
  • the senor can be used to determined the time period during which the sample is taken in order to achieve a desired sample volume. Furthermore, if it desirable to take samples having the same volume during a constant time period and at a constant time interval, the sensor can be connected to a pumping means.
  • the pumping means can be arranged at the specimen collector between the test site and the test tube. This pumping means is preferably controlled or regulated by means of the sensor.
  • the measured pressure can be used to determined the flow rate at the outlet, which information can be used as an input to the pumping means.
  • the pumping means can be arranged to change the flow rate to a desired flow rate in order to take the desired sample volume at a desired time point and during a desired time period.
  • FIG. 2b A schematic second embodiment of a specimen taking device or sample taking device will now be described with reference to Fig. 2b.
  • This embodiment of the specimen taking apparatus in accordance with the invention comprises in addition to the hollow specimen collector 120 and the test tube 140 as described above with reference to Fig.
  • a test solution source 150 comprising a test solution 152 which can be supplied to an inlet 134 of the test site 130 via a hollow solution supplier 160.
  • the test solution source 150 can for example be realised as an air-proof container or a receptacle having an air-tight sealing.
  • the solution supplier 160 comprises a proximal end 162 with an outlet, which proximal end 162 is connectable to an inlet 134 of the test site 130 of the test object 1, and a distal end 164 having an inlet, which distal end 164 is connectable to the solution source 150.
  • a test solution 152 can be transported from the inlet of the distal end 164 to the outlet of the proximal end 162 through the solution supplier 160 by means of for example a pumping means 166 such as a peristaltic pump.
  • the pumping means 160 is able to provide a desired flow rate of the supplied test solution needed for the experiment or study.
  • a dialysis membrane e.g. a tubing having an inlet, an outlet in and a permeable wall, can be percutaneously arranged under the skin of a test object.
  • a test solution e.g.
  • a dialysate can be supplied to the inlet of the tubing and can further be arranged to flow to the outlet of the tubing, whereby the test solution will penetrate the permeable wall and mix with the body fluid surrounding the tubing when it is arranged at the test site. Further, the body fluid surrounding the tubing will penetrate the permeable wall and mix with the test solution flowing inside of the tubing.
  • a sample i.e. a mixture of test solution and body fluid
  • the desired flow rate of the supplied test solution should be low enough for the supplied test solution to penetrate the permeable wall of the tubing and thus the desired flow rate should be low enough to provide samples that are representative for the concentration of the test solution in the test site, i.e. to provide samples that have a concentration of the test solution that corresponds to the concentration of the test solution in the test site.
  • a suitable flow rate can be in the range of 1 microlitre per minute. Thus it will take approximately 20 minutes to get a total sample volume in a test tube of approximately 20 microlitres. However, if the flow rate of the supplied test solution is too high the concentration of the test solution in the taken samples will be lesser than the concentration in the cells and thus a non- representative sample is taken. In Fig.
  • the flow rate of the supplied test solution 152 is controlled by means of an overpressure in the solution source 150, i.e. the pressure in the solution source 150 is higher than the pressure on the outside of the solution source 150.
  • the over pressure is achieved by supplying a preselected or predetermined volume of a gas or a gas mixture 172 to the solution source 150 by means of a gas supplier 170.
  • the gas supplier 170 can for example be realised as a syringe or a container comprising the gas or gas mixture.
  • a gas volume of 1 millilitres is supplied to a solution source having a total volume of 1 millilitre and comprising 200 microlitres of a test solution
  • the pressure in the solution source will increase with 20 %. This increased pressure will result in a variation of the achieved flow rate of 20 % which in some cases is too high and a not acceptable flow rate variation.
  • a gas volume of 5 millilitres is supplied to the solution source having a total volume of 1 millilitre and comprising 200 microlitres of a test solution, the pressure will increase with 4 % and a flow rate variation of 4 % is achieved.
  • an acceptable flow rate variation e.g.
  • test solution source 150 is configured as a tube or a tubing and comprises a proximal end 154 having an outlet and a distal end 156 having an inlet. Further, the proximal end 154 of the solution source 150 is connectable to the distal end 164 of the solution supplier 160. Furthermore, in the cavity defined by the inner walls of the solution source 150 between the proximal end 154 and the distal end 156 the test solution 152 is comprised.
  • the distal end 156 of the solution source 150 is configured to be connected to the outlet of a gas supplier 170 comprising a gas or a gas mixture 172 having an over pressure, i.e. the pressure in the gas source 170 is higher than the pressure on the outside of the gas source 170.
  • the gas supplier 170 can be realised as an air-proof container or reservoir having an air-tight sealing.
  • the solution source 150 is configured as a tube or tubing, which can be manufactured of Teflon ® or another suitable plastic or plastic-like material that does not or minimally affect the test solution negatively.
  • the solution source 150 is preferably manufacture of a flexible material, i.e. of a material that can be bent or rotated easily without breaking.
  • the inner diameter of the solution source 150 is in the range of 0,5 - 3 millimetres, preferably approximately 1 millimetre. However, it should be understood that the inner diameter of the solution source 150 can be varied dependent on inter alia the desired volume and flow rate of the test solution to be supplied. Usually, it is desirable to provide an inner diameter of the solution source 150 that is much larger than the inner
  • the inner diameter of the solution supplier 160 is in the range of 0,1 millimetre or less, a suitable inner diameter of the solution source 150 is approximately 1 millimetre.
  • the solution source 150 is further configured in such a way that the test solution 152 is provided as a liquid column in the flexible solution source 150.
  • the solution source 150 can be helical or provided with a helical-like shape.
  • the solution supplier 160 and solution source 150 can be bent or turned without risking that the gas supplied to the solution source 150 from the gas supplier 170 passes by parts of the test solution 152 in the solution source 150.
  • the laboratory animal can move freely and the risk of gas
  • Fig. 2d shows a schematic fifth embodiment of the inventive sample taking device.
  • an outlet of a second gas source 180 comprising a gas or gas mixture 182 is connected to an inlet of a first gas source 170 by means of a tube or a tubing 192.
  • the gas pressure p2 in the second gas reservoir 180 is larger than the gas pressure pi in the first gas reservoir 170, i.e. p2 > pi , entailing a gas flow from the second gas reservoir 180 to the first gas reservoir 170.
  • gas flow control means 190 is arranged at the tubing 190, which gas flow control means 190 is configured to control or regulate the gas flow from the second gas source 180 to the first gas source 170.
  • the gas flow control means 190 can for example comprise or be realised as a valve having an open position, which enables a gas flow between the gas sources 170, 180, and a closed position, which prevents the gas flow.
  • the gas flow control means 190 can also be arranged to have one or several intermediate positions, whereby the flow rate of the gas can be varied.
  • a clip or a pliers e.g. a forceps, is realising the gas flow control means 190, whereby the gas flow can be regulated by means of the clip or the pliers.
  • a sensor 174 can be arranged at the first gas reservoir 170.
  • the sensor 174 is arranged to detect or register the pressure in the first gas reservoir 170. Further, information about the pressure in the first gas source 170 can then be used as an input to the gas flow control means 190, whereby the gas flow control means 190 can be configured to control the gas flow from the second gas source 180 to the first gas source 170 dependent on the pressure in the first gas source 170. This can be an essential feature of the gas flow control means 190 since the pressure in the first gas source 170 determines the flow rate of the test solution 152 comprised in the test solution source 150.
  • a higher pressure in the first gas source 170 entails a higher flow of the test solution. Further, the flow rate of the test solution can be determined if one knows the pressure in and the volume of the first gas source 170.
  • a schematic sixth embodiment of the inventive sample taking device will be described with reference to Fig.2f.
  • a pumping means 166 is arranged at the solution supplier 160 between a solution source 150 and a test site 130 of the laboratory animal.
  • the pumping means 166 is further arranged to control the flow rate of a test solution 152 from the solution source 150 to the test site 130, and can be realised as a liquid pump, a diaphragm pump or a membrane pump.
  • a first gas source 170 comprising a sensor 174 is, by means of a tubing 176 and for example a T-connection, connected to the solution supplier 160 between the pumping means 166 and the test site 130.
  • the sensor 174 is arranged to detect or measure the pressure in the gas source 170.
  • the sensor 174 is communicatively connected or coupled to the pumping means 166, whereby the functioning of the pumping means 166 can be controlled dependent on the measured pressure in the first gas source 170.
  • the pumping means 166 is arranged to pump a test solution 152 from the test solution source 150 through the solution supplier 160 and towards the test site 130.
  • the test solution 152 will also flow into the tubing 176 towards the first gas source 170.
  • the tubing 176 is able to comprise a sufficient volume.
  • the volume of the tubing 176 is for example equal to or almost equal to the volume of the gas source 170.
  • the volume of the tubing 176 is such that when the sensor 174 registers a maximum pressure in the gas source 170, the test solution 152 in the tubing 176 has not reached the gas source 170. Then, the pumping means 166 is turned off and the overpressure in the gas source 170 will cause the test solution comprised in the tubing 176 to flow towards the test site 130.
  • the solution source 150 can according to an embodiment of the invention be connected to or integrated with a reservoir 150', which can comprise a test solution 152' or be refillable with a test solution 152' .
  • the solution source and the tubing is preferably manufactured of a flexible material and configured to be helical or to have a helical-like shape.
  • the solution supplier 160, the solution source 150 and the tubing 176 can be bent or turned without risking that the supplied gas passes by parts of the test solution and is supplied to the test site.
  • the laboratory animal can move freely and the risk of supplying gas bubbles to the test site is avoided.
  • a specimen taking device 300 for taking of e.g. blood samples is schematically shown in Fig. 3.
  • an proximal end 322 of a first part 320a of a sample collector 320 having a lumen is inserted into a test site, e.g.
  • a distal end 324 of the first part 320a of the sample collector 320 is connected to a flow control means 330, for example realised as a valve.
  • the flow control means 330 is configured to have at least two positions, a first position providing a fluid flow between the distal end 324 of the first part 320a and a proximal end 325 of a second part 320b of the sample collector 320, while the fluid flow between the distal end 324 and a proximal end 327 of a third part 320c of the sample collector 320 is blocked.
  • the second position of the valve 330 provides a fluid flow between the distal end 324 of the first part 320a and the proximal end 327 of the third part 320c of the sample collector 320, while blocking fluid flow between the distal end 324 and the proximal end 325 of the second part 320b of the sample collector 320.
  • the second part 320b of the sample collector 320 is connected to a solution source 350 via a pumping means 360, e.g. realised as a peristaltic pump or the like.
  • the second part 320b is configured to have a distal opening or inlet in a distal end 326, whereby a rinsing solution 352, e.g.
  • the pumping means 360 is arranged to provide a flow of a fluid, e.g.
  • the valve 330 can be in its first position, blood can be transported in a lumen of the sample collector 320 to the second part 320b.
  • the valve 330 can be switched to be in its second position.
  • the volume of the blood comprised in the second part 320b constitutes the blood sample and can be transported to the third part 320c by means of the pumping means 360.
  • the taken blood sample can be supplied to a test tube 340, via a distal opening or outlet in a distal end 328 of the third part 320c, by means of the pumping means 360.
  • the method of taking a blood sample comprised the steps of (cf. Fig. 4):
  • a rinsing solution which is not harmful to the laboratory animal, e.g. a solution comprising sodium chloride;
  • test site e.g. a blood vessel, of the laboratory animal
  • 402 setting the flow control means 330 in a first position, in which position the connection between the first part 320a and the second part 320b is open; 403 extracting blood from the laboratory animal 301 to the second part 320b of the sample collector 320 via the inlet of the proximal end 322 of the first part 320a, whereby the volume blood comprised in the second part 320b constitutes the blood sample; 404 setting the flow control means 330 in a second position, in which position the connection between the second part 320b and the third part 320c is open;
  • a rinsing solution not harmful to the laboratory animal 301 is supplied to the lumens of the sample collector 320.
  • the rinsing solution can for example comprise a sterile sodium chloride solution or a Ringer's acetate solution.
  • the proximal end 322 of the first part 320a is introduced into a blood vessel of the laboratory animal.
  • the flow control means 330 is in step 402 set in a first position enabling fluid flow between the first part 320a and the second part 320b of the sample collector 320, while prohibiting fluid flow between the first part 320a and the third part 320c.
  • Blood is then in step 403 extracted from the laboratory animal 301 to the second part 320b of the sample collector 320 via the inlet of the proximal end 322 of the first part 320a, whereby the volume blood comprised in the second part 320b constitutes the blood sample.
  • the flow control means 330 is in step 404 set in a second position enabling fluid flow between the second part 320b and the third part 320c of the sample collector 320, while prohibiting fluid flow between the first part 320a and the second part 320b.
  • step 405 the distal end 328 of the third part 320c is moved to a location at a waste container (not shown).
  • the blood sample comprised in the second part 320b is then in step 406 transported to an outlet in a distal end 328 of the third part 320c of the sample collector 320, whereby the rinsing solution comprised in the lumen of the third part 320c is supplied to the waste container.
  • the taken sample is comprised in the third part 320c from the opening in the distal end 328 of the third part 320c towards the flow control means 330.
  • the distal end 328 of the third part 320c is in step 407 moved to be located at a test tube 340 in such a way that the blood sample can be supplied to the test tube 340 in step 408.
  • the distal end 328 of the third part 320c is then in step 409 moved to a location at the waste container in such a way that a volume of the rinsing solution 352 in step 410 can be transported from the solution source 350 to the waste container via the second 320b and third 320c parts of the sample collector 320.
  • the flow control means 330 is set in the first position, whereby the blood comprised in the first part 320a and a volume of the rinsing solution 352 in step 412 can be supplied to the laboratory animal 301.
  • the volume of the rinsing solution supplied to the animal is preferably approximately equal to the volume of the taken blood sample in order to restore the fluid balance of the laboratory animal.
  • step 413 if a further sample is to be taken the steps are repeated from step 403 after a preset time period otherwise the sample taking procedure is ended in step 414.
  • an air bubble can be used to separate the extracted sample from the rinsing solution comprised in the sample collector 320.
  • Such a method can comprise the steps of (cf. Fig. 5):
  • a rinsing solution which is not harmful to the laboratory animal 301, e.g. a solution comprising sodium chloride;
  • 501 introducing the proximal end 322 of the first part 320a into a test site, e.g. a blood vessel 310, of the laboratory animal;
  • 504 setting the flow control means 330 in the first position, in which position the connection between the first part 320a and the second part 320b is open; 505 extracting blood from the laboratory animal 301, via the opening in the proximal end 322 of the first part 320a, to a distal end 324 of the first part 320a adjacent to the flow control means 330;
  • a rinsing solution not harmful to the laboratory animal 301 is supplied to the lumens of the sample collector 320.
  • the rinsmg solution can for example comprise a sodium chloride solution or a Ringer's acetate solution.
  • Confer Fig. 6a showing the contents of the three parts 320a - 320c after step 500.
  • the proximal end 322 of the first part 320a is introduced into a test site, e.g. a blood vessel, of the laboratory animal.
  • the flow control means 330 is in step 503 set in the second position, i.e.
  • the pumping means 360 is in step 502 actuated in such a way that a first air bubble is sucked into the proximal end 325 of the second part 320b via the opening in the distal end 328 of the third part 320c.
  • This first air bubble can be detected by a sensor means (not shown) arranged at the pumping means 360 whereby the pumping means 360 can be controlled to stop pumping fluid in the direction towards the solution source 350.
  • step 504 the flow control means 330 is set in the first position enabling a fluid flow between the first part 320a and the second part 320b, while preventing a fluid flow between the first part 320a and the third part 320c.
  • Blood is then in step 505 extracted from the laboratory animal 301 to a distal end 324 of the first part 320a via the opening in the proximal end 322 of the first part 320a.
  • the volume of the extracted blood is such that the distal end 324 of the first part 320a, which distal end 324 is adjacent to the flow control means 330, comprises blood.
  • Confer Fig. 6c showing the contents of the three parts 320a - 320c after step 505.
  • blood can be extracted into the second part 320b, but the blood will then be mixed with the rinsing solution comprised in the second part 320b.
  • Such a mixture of blood and rinsing solution is sometimes called waste solution.
  • step 506 the flow control means 330 is set in the second position and in step 507 the pumping means 360 is actuated in such a way that a second air bubble is sucked into the proximal end 325 of the second part 320b via the third part 320c.
  • Confer Fig. 6d showing the contents of the three parts 320a- 320c after step 507.
  • the flow control means 330 is then in step 508 set in the first position and the blood comprised in the first part 320a is in step 509 transported to the second part 320b of the sample collector 320.
  • the volume blood comprised in the second part 320b constitutes the blood sample.
  • Confer Fig. 6e showing the contents of the three parts 320a - 320c after step 509.
  • step 510 the flow control means 330 is set in the second position and in step 511 the blood sample is transported to an outlet in the distal end 328 of the third part 320c of the sample collector 320.
  • the blood sample is located in the third part 320c from the outlet in the distal end 328 of the third part 320c towards the flow control means 330.
  • Confer Fig. 6f showing the contents of the three parts 320a - 320c after step 511.
  • the distal end 328 of the third part 320c is in step 512 moved to a test tube 340, whereby the blood sample in step 513 can be supplied to the test tube 340 by means of the pumping means 360.
  • Confer Fig. 6g showing the contents of the three parts 320a- 320c after step 513.
  • the distal end 328 of the third part 320c is in step 514 moved to a waste container and in step 515 rinsing solution 352 is supplied from the solution source 350 to the waste container via the second 320b and third 320c parts.
  • the length of the second part 320b between the flow control means 330 and the pumping means 360 is long enough to comprise a volume corresponding to the sum of volume of a solution comprised in the first part 320a, the volume of a the waste solution i.e. a the solution between the first and second air bubble, the volume of the air bubbles and the volume of the fluid sample. It should be understood that the some of the steps described above with reference to the Figs. 4 and 5 can be performed in a different order and that the flow rate can be different in different parts of the sample collector.
  • an embodiment of the sample taking device comprises further a test solution source having a test solution which can be supplied to the laboratory animal via the second 320b and first 320a parts of the sample collector 320 as described above.
  • the second part 320b can comprise two branches in its distal part, whereby rinsing solution can be supplied via a first branch and test solution via a second branch.
  • the test solution comprising e.g.
  • sample taking device for pharmacokinetic studies is configured as a combination of the sample taking device as described with reference to Fig. 3 and one of the sample taking devices as described with reference to Figs. 2b - 2f.
  • the test solution is supplied to the laboratory animal via the solution supplier by means of a pumping means as described above with reference to Figs. 2b - 2f.
  • the sample taking procedure is performed using components of the sample taking device according to Fig. 3 and the method according to Fig. 4 or 5.
  • the sample taking device 100, 300 can further comprise a support plate 710 having a first side 711 and an opposite second side 712.
  • the support plate 710 has a rectangular shape and the first and second sides 711, 712 have surfaces that are approximately parallel.
  • a nut 713 e.g. a ball nut
  • a bearing 714 such as a ball bearing
  • a first cog wheel or tooth wheel 715 is arranged at the ball nut 713.
  • the first tooth wheel 715 is pressed on to the ball nut 713.
  • the ball nut 713 when the first tooth wheel 715 is rotated, the ball nut 713 will rotate.
  • the ball nut 713 is further arranged at a screwed rod or bar 716, such as a ball nut screw, which will be moved along its longitudinal axis when the ball nut 713 is rotated. Since the ball nut 713 is mounted in the bearing 714, the ball nut 713 will not be moved along its longitudinal axis but only rotated around its longitudinal axis, implying that the ball nut screw 716 will be moved along its longitudinal axis and not rotated. The direction of the movement depends on the direction of the rotation.
  • a second cog wheel or tooth wheel At the first side 711 of the support plate 710 is a second cog wheel or tooth wheel
  • First ends of the ball nut screw 716 and the linear axle 719 are rigidly attached to a first fixing plate 721 and arranged approximately parallel to each other.
  • the movement control means when the second tooth wheel 717 is rotated by means of the stepping motor 720, the first tooth wheel 715 is rotated and the ball nut screw 716 is moved along its longitudinal axis. Further the linear axle 719 is correspondingly moved along its longitudinal axis due to the fixing plate 721. According to the embodiment shown in Figs. 7a-7d, the movement control means
  • the 720 is arranged at the second side 712 of the support plate 710, at which second side 712 a housing 730 is arranged.
  • the housing 730 is arranged turnable around its longitudinal axis and configured to uphold a fraction assembler 740.
  • the fraction assembler 740 is configured to be removably attached to the housing 730 of the support plate 710 of the sample taking device.
  • the fraction assembler 740 is further configured to comprise one or several test tubes (not shown) for storing samples and waste solution. It should be understood that the waste container mentioned above can be realised as one of the test tubes comprised in the fraction assembler.
  • the first fixing plate 721 comprises a delivery means 750, having a lumen, a proximal and a distal end openings.
  • the delivery means is according to an embodiment stiff or rigid and is for example realised as a hollow needle.
  • the delivery means 750 is further movable along its longitudinal axis through a hole 709 in the support plate 710.
  • the distal end 124, 328 of the specimen collector 120, 320 is further connectable to the proximal end 752 of the delivery means 750.
  • the distal end 754 of the delivery means 750 is devised to deliver a taken specimen or a waste solution to a test tube 140, 340 or a waste container, respectively, comprised in the fraction assembler 740.
  • a sample or a waste solution comprised in the lumen of the sample collector 120, 320 can be supplied to a test tube 140, 340 or a waste container via the lumen and the distal end opening of the delivery means 750.
  • the delivery means is configured as a guiding means for the specimen collector, such as an introducer sheath.
  • the distal end of the sample collector is inserted through the delivery means such that a distal tip of the sample collector is positioned distally of the distal end opening of the delivery means.
  • the delivery means 750 is fixedly arranged at the first fixing plate 721 which is fixedly attached to the linear axle 719 and to the ball nut screw 716.
  • the linear axle 719 and the ball nut screw 716 are movably arranged at the support plate 710 such that they can be moved along their longitudinal axis through holes in the support plate 710.
  • the delivery means 750 is arranged to be movable along its longitudinal axis and the control means 720 is arranged to control the movement of the delivery means 750 and to control the position of the delivery means 750.
  • the control means 720 is realised as a stepping motor 720 and a power source (not shown) is arranged to supply electrical pulses to the stepping motor 720.
  • the power source can be realised as a battery, e.g. a rechargeable battery.
  • the stepping motor 720 is arranged to provide a step-by-step movement of the delivery means 750 and in some studies a step length of approximately 1 millimetre is suitable.
  • a sensor 722 is further communicatively connected to the stepping motor 720, which sensor 722 detects the position of the delivery means 750.
  • the sensor 722 can for example be realised as a micro switch.
  • the delivery means 750 can be moved between a first position and a second position. In the first position, the delivery means 750 is retracted and in the second position the delivery means 750 is extended. If a test tube or a waste container comprised in the fraction assembler 740 is arranged at a location suitable for delivery of a solution, i.e.
  • the longitudinal axis of the test tube or waste container approximately coincide with the longitudinal axis of the delivery means 750, and the delivery means 750 is in the first position, the distal tip of the delivery means 750 is located outside of the test tube 140, 340 or waste container.
  • the distal tip of the delivery means 750 is inserted into the test tube 140, 340 or waste container and located close to the inner bottom thereof.
  • the delivery means 750 is moved stepwise during the delivery of the solution from the second position towards the first position. This stepwise movement of the delivery means 750 continues until the total volume of the solution has been delivered.
  • the delivery means 750 When the delivery of the sample is completed the delivery means 750 is retracted to its first position. In some studies it is desirable to avoid air bubbles in the sample comprised in the test tube. To avoid or minimise the risk air bubbles, the movement of the delivery means is preferably controlled in such a way that the distance between the tip of the delivery means and the surface of the delivered sample is shorter than the distance between the outer surface of the delivery means and the inner wall of the test tube. Further, second ends of the ball nut screw 716 and the linear axle 719, located on the second side 712 of the support plate 710, are rigidly attached to a second fixing plate 723, cf. Fig. 7d.
  • the second fixing plate 723 When the delivery means 750 is moved from its second position towards the first position, the second fixing plate 723 is moved towards the second side 712 of the support plate 710 and the sensor 722 will detect the second fixing plate 723. Thus the sensor 722 will indicate that the delivery means 750 is in its first position and the movement of the delivery means 750 will stop. Further, when the delivery means 750 is moved from its second position to its first position, the second fixing plate 723 is moved towards the housing 730 of the support plate 710. According to an embodiment, the housing 730 has a saw-toothed shape and the fixing plate 730 comprises a pin 724, cf. Figs. 7a and 7d.
  • the pin 724 and the saw-toothed shape of the housing 730 is further configured in such a way that the pin 724, when moved towards the support plate 710, will engage the housing 730 resulting in a rotation of the housing 730.
  • the fraction assembler 740 is arrangeable in the housing 730 in such a way that it will rotate around its longitudinal axis together with the housing 730.
  • the rotation of the fraction assembler 740 corresponds to the rotation of the housing 730.
  • the distance between the teeth corresponds approximately to the distance between two test tubes comprised in the fraction assembler 740, implying that after the rotation a new test tube will be located in a position suitable for delivery of a sample.
  • the fraction assembler 740 can be rotated when the delivery means 750 is in the first position after the delivery of a first sample to a first test tube, whereby a second test tube is moved to a position in which the deliver means 750 is capable of delivering a second sample to the second test tube.
  • magnets can for example be arranged to rotate the housing in place.
  • the housing 730 comprises a set of magnets 731, which are evenly distributed such that each magnet 731 corresponds to a position of a test tube comprised in an attached fraction assembler.
  • a magnet 726 is further arranged at the second side 712 of the support plate 710 and outside the housing 730, cf. Fig. 7c and 7d.
  • the magnets 731 are preferably permanent magnets having a magnetic pole outwards that is opposite of an inwards magnetic pole of the magnet 726 arranged at the support plate 710. If the housing 730, by means of the stepping motor 720 and the pin 724 of the second fixing plate 723, is rotated, the magnet 731 closest to the magnet 726 and the magnet 726 will rotate the housing 730 to a position in which the magnet 731 and the magnet 726 of the support plate 710 are facing each other.
  • the control means 720 can further comprise a second sensor 725 configured to operate as a revolution counter.
  • the sensor 725 is realised as a micro switch.
  • the outer surface of housing 730 can comprise a small cavity or a protrusion, or the like, which is arranged to be detected once per revolution by the sensor 725.
  • Figs 8a - 8d show schematically a fraction assembler 740 having an approximately cylindrical shape.
  • a number of openings 741 for test tubes and a centrally located recess or depression 742 for mounting at a projection or protrusion 732 of a housing 730 are provided, cf. also Fig 7e. That is the recess 742 is functioning as a female connector and the protrusion 732 as a male connector.
  • the friction between the surface of the recess and the surface of the protrusion is not sufficient to hold the fraction assembler.
  • the fraction assembler 740 can held in position at the housing 730 by means of a magnet 743 at the recess 742 and a magnet 733 at the protrusion 732. Further, in order to correctly position the fraction assembler 740 in the housing, the fraction assembler can be provided with a set of through holes 744 having a configuration corresponding to a configuration of a set of through holes 734 in the housing 730 and the support plate, whereby rods or the like can be inserted through the holes.
  • the holes can have different configuration entailing that only a fraction assembler having a special configuration of holes can be attached to a certain housing.
  • a part of the fraction assembler 740 can be provided with a slot or a slit 745 in an outer surface thereof, as shown in Fig. 8d.
  • the slot 745 is arranged along the circumference of the outer surface of the fraction assembler 740.
  • a set of through holes 746 are provided in the slit 745, which holes 746 are evenly distributed in the slit 745 and the position of each of the holes 746 corresponds to the position of a hole 741 for a test tube.
  • An O-ring or an elastic band (not shown) can be arranged in the slit 745 to fasten the test tubes when positioned in the fraction assembler.
  • a hole (not shown) can be arranged in each opening 741 for a test tube.
  • the hole has a diameter that is smaller than the diameter of the opening 741.
  • the fraction assembler can be loaded with test tubes which are cooled down to a desired temperature in order to better preserve the taken samples.
  • the fraction assembler can be filled with an internal medium, such a water, and cooled to for example approximately -1 degree Celsius before the start of the sample taking procedure, whereby the water freezes. The melting heat can then be used to cool the test tube and thus to preserve the taken samples.
  • the fraction assembler is according to an embodiment comprised in an insulating covering or housing, such as a Frigolit ® housing, during the sample taking procedure in order to maintain the temperature of the fraction assembler.
  • the sample taking device has diametrical dimensions of approximately 45x35x80 millimetres (width, depth, height). However, it should be understood that the dimensions can be varied dependent on for example the size of the test object or the kind of study to perform.
  • the components of the sample taking device is conveniently arranged to minimise the size of the sample taking device . Further the components are manufactured of suitable materials having a low- weight. Furthermore, the components of the sample taking device is conveniently arranged in such a way that disposables, e.g. a solution source or a gas source, easily can be inserted, removed or replaced, and such that necessary tubings easily can be connected to for example the solution or gas source. Disposables Some of the components described above, for example the specimen collector, the tubings, the solution source or the gas source, are conveniently realised as disposable articles made in suitable materials.
  • the specimen collector 120, 320 and the solution supplier 160, 320 can be realised as one or several catheters, tubes or tubings and the proximal end thereof can for example be introduced into the test site by means of a non-invasive technique using e.g. an introducer or by surgical cut-down.
  • the part or parts of the specimen collector 120, 320 and the solution supplier 160, 320 introduced into the test object are manufactured of a biocompatible material or another suitable material that do not or minimally affect the test object or the taken samples adversely, e.g. a material having a low or non-adhesive, low or non-reactive and low or non-contaminating characteristics.
  • the lumen of the specimen collector is preferably treated or coated with a substance comprising an anticoagulant minimising the risk of blood clotting in the sample collector.
  • the solution source can for example comprise a sodium chloride solution, a Ringer's solution or a test solution.

Abstract

The present invention relates generally to automatic collection of a specimen from a subject of an experiment, such as a living being. More specifically, the invention relates to automatic collection of a specimen having a minimised influence on the normal behaviour and movement of the living being. (Fig 1a and 1b)

Description

COLLECTION OF A SPECIMEN
Technical field The present invention relates generally to automatic collection of a specimen from a subject of an experiment, such as a living being. More specifically, the invention relates to automatic collection of a specimen having a minimised influence on the normal behaviour and movement of the living being.
Background of the invention In medical science and pharmaceutical industry there is often a need for testing the reaction of drugs or treatments in living beings, for example test objects in the shape of laboratory animals such as rats, dogs or pigs used for experimental purposes. In such cases it is common to take a plurality of samples or specimens from the test object as well as injecting substances into the test object during the course of hours or days, in order to allow observation of gradual responses in the test object. In order to minimise time and cost consuming manual handling of taking specimen as well as the stress impact of such a manual handling on the laboratory animal, attempts have been made to automate the sample taking procedure. There is also an application in monitoring animals or human beings during medical treatment. Today's sample taking systems or devices is not portable and comprises often sample taking components, such as valves, pumps and test tubes, arranged at a distance from the laboratory animal. The distance between the laboratory animal and the sample taking components requires that the tubings or the like connected between the laboratory animal and the sample taking components have to be quite long to provide free movement of the animal. Further, the long tubings often require that the volume of a taken specimen has to be quite large due to the long distance the taken sample has to be transported in the tubings. However in many cases, the volume of the taken specimen or sample need to be very small, and especially when the specimen is taken from small laboratory animals. When for example taking a blood sample from a rat or a dog the volume of the taken sample is usually in the range of 25 - 250 microlitres or 100 - 500 microlitres, respectively. Further, when taking a bile sample from a rat the volume is usually in the range of 100 - 500 microlitres depending on for example the time period for the sampling or the kind of study. When taking or collecting a specimen having a small volume from a subject of an experiment to a test tube there are several problems to be solved. A problem to be solved is to provide sample taking on a freely moving laboratory animal in order to minimise the effect of the sample taking procedure on the animal. Another problem to be solved is to provide taking of samples having a small volume. Yet another problem to be solved when providing a portable sample taking device is to minimise the need of power supply. A problem to be solved in embodiments of the invention is to control the rate of a supplied solution through a test site of a subj ect of an experiment. Another problem to be solved is to avoid air bubbles in the taken specimen comprised in the test tube. Yet another problem to be solved is to minimise the risk of contaminating the outer surface of the means, e.g. a hollow needle, delivering the sample to the test tube, which contamination occurs if the outer surface of the needle during the delivery of the sample is in contact with a part of the sample already delivered to the test tube. It is critical to avoid such a contamination of the outer surface of the hollow needle since in the case of taking multiple samples, which are dispensed to different test tubes, the contamination of the outer surface of the needle will also contaminate the subsequent samples.
Object of the invention The overall object of the present invention is to solve among others the above mentioned problems of automatically collecting a specimen from a subject of an experiment, i.e. from a living test object, with a minimised influence on the normal behaviour and movement of the test obj ect. More specifically embodiments of the present invention provides a portable sample taking device providing taking of a sample having a small volume, and seeks to control the taking of a specimen to receive a specimen of hig quality and a specimen that is representative for the fluid or solution from which the specimen is taken, to reduce the power consumption, to avoid air bubbles in a taken specimen and/or to minimise unintentional contamination of a taken specimen. Summary of the invention The stated problems, among others, are solved by embodiments of the present invention by providing i.a. an automatic specimen taking system and a portable specimen taking device according to the independent claims. Further embodiments of the invention are defined in the dependent claims. A further aspect of the invention is directed to a computer program product for use in a data processing system and devised for controlling automatic specimen taking in accordance with the inventive method. The computer program product comprises computer program code portions, possibly stored on a storage medium and devised to control the data processing system to control the specimen taking apparatus to perform the steps of the inventive method.
Definitions In the description text, the following definitions will be used. The distal and the proximal parts of a component refer to the parts of the component that are farthest from and closest to a subject of an experiment, respectively.
Brief description of drawings Embodiments of the invention will be described with reference to the following drawings, in which:
Fig. la schematically shows an embodiment of a specimen taking system according to the present invention;
Fig. lb schematically shows an embodiment of a specimen taking device according to the present invention attached to a laboratory animal; Fig. 2a schematically shows a first embodiment of a specimen taking device according to the present invention;
Fig. 2b schematically shows a second embodiment of a specimen taking device according to the present invention;
Fig. 2c schematically shows a third embodiment of a specimen taking device according to the present invention;
Fig. 2d schematically shows a fourth embodiment of a specimen taking device according to the present invention;
Fig. 2e schematically shows a fifth embodiment of a specimen taking device according to the present invention; Fig. 2f schematically shows a sixth embodiment of a specimen taking device according to the present invention;
Fig. 3 schematically shows an embodiment of a specimen taking device configured to take blood sample according to the present invention; Fig. 4 shows a flow chart of method steps for taking a blood sample;
Fig. 5 shows another flow chart of method steps for taking a blood sample;
Fig. 6a-6i schematically show the contents in a sample collector at different steps during the method described in conjunction with Fig. 5;
Fig. 7a schematically shows a side view of components of a specimen taking device according to the present invention;
Fig. 7b shows schematically a perspective view of components of a specimen taking device according to the present invention;
Fig. 7c shows schematically another side view of components of a specimen taking device according to the present invention; Fig. 7d shows schematically a view of components of a specimen taking device according to the present invention taken from the fraction assembler;
Fig. 7e shows schematically a view of a housing according to the invention; and
Fig. 8a and 8b schematically shows a perspective view and a top view, respectively, of a fraction assembler according to the invention;
Detailed description of embodiments The present invention refers to automatic collection of a specimen from a subject of an experiment, such as a living being. More specifically the invention refers to automatic collection of a specimen entailing a minimised influence on the normal behaviour and movement of the living being. The described embodiments of the invention are directed to collecting, sampling or taking liquid specimen from for example a vessel or a tissue structure in a subject of an experiment or from some other kind of structure containing a fluid or a liquid substance.
For example, embodiments of the invention are used for taking samples of urine, bile, or blood. However, with a modification the apparatus according to the invention may be adapted to collect solid material samples from a test object. The subject of an experiment is in most cases a living being, such as a laboratory animal. Dependent on the kind of experiment to be performed, different laboratory animals are used, but rats, mice, dogs and pigs are among the most frequently used laboratory animals. Exemplifying embodiments of the invention will be described below with reference to the accompanying drawings in which the laboratory animal is a pig or a dog, but it should be understood that the laboratory animal can be another kind of animal and that a described embodiment is not restricted to apply only to the animal shown in the figure referred to in the description text. Further, the subject of an experiment can also refer to another subject or test object that is exposed to repetitive taking of samples, such as a container comprising a liquid, consistent or solid test material. Embodiments of the present invention will be described below with reference to the accompanying drawings, in which drawings the same reference numerals are used for components or functions that are identical or correspond to each other. It should also be emphasised that the term "comprising/comprises" when used in this description text is taken to specify the presence of stated features, steps or components but does not preclude the presence of one or more other features, integers, steps, components or groups thereof.
Specimen taking system With reference to Fig. la, a general embodiment of a specimen taking system according to the invention will be described. The specimen taking system 10 comprises one or several specimen taking apparatuses or sample taking devices 100 each, of which is portable and removably attached to a subject of an experiment, for example a laboratory animal. As schematically illustrated in Fig. lb, the sample taking device 100 can be removably attached around the neck of the laboratory animal 1 by means of a necklace 101 having a Velcro® fastening or snap locking. However, the sample taking device 100 can of course be removably attached to another body part or in another way, but the sample taking device 100 is preferably attached to the subject of the experiment in such a way that the normal behaviour or movement of the living being is not disturbed. The sample taking system 10 comprises further one or several computerised units
102, 104 which are communicatively connected, e.g. by means of a wired or a wireless communication link 106, to a sample taking device 100. The wireless communication link 106 can for example be based on radio wave, infrared (IR) or bluetooth technique. The computerised unit 102, 104 can for example be a personal computer (PC) 102, a portable computer 104, such as handheld computer or a personal digital assistant (PDA), a laptop or a palmtop. The sample taking device comprises means for taking and storing one or several specimens, a communication interface, a micro processor, a storing means and electronics. Embodiments of the sample taking device can further comprise a solution source and means for supplying a solution from the solution source to a test object. Some embodiments of the sample taking device can comprise a gas source and means for supplying gas from the gas source. Further, the sample taking device comprises a power source, such as a battery, arranged to provide power to components of the sample taking device. The battery can be rechargeable. Embodiments of the personal computer 102 can comprise means for inputting data or information, user interface, communication interface, means for storing information concerning for example information relating to a laboratory animal and test schemes, i.e. information relating to the laboratory animal, when to take a specimen, the time interval between consecutive specimens, the volume of the specimen to be taken, the number of specimen to be taken, etc. The information can for example be stored in a database 103 communicatively connected to the computerised unit 102. Further, the computerised unit 102, 104 can be arranged to control the taking of one or several specimens. Thus the computerised unit 102, 104 can be arranged to start, stop or pause the taking of specimen. Furthermore, the computerised unit 102, 104 can be arranged to read information relating to the study from the sample taking device. In an embodiment of the invention, the information stored in the computerised unit 102, 104 which relates to a study of a specific laboratory animal can be transmitted from the computerised unit 102, 104 to a sample taking device 100 of the specific laboratory animal. Thus, the sample taking device 100 comprises means for receiving and storing the information, e.g. test schemes, means for taking and storing specimens, and means for controlling the taking of the samples according to a test scheme. Furthermore, the sample taking device 100 can be arranged to store information relating to the taken sample, e.g. the point of time when the sample was taken and the volume of the sample, in a storage means which can be comprised in the sample taking device. According to an embodiment of the invention, the sample taking system 10 further comprises another computerised unit 105, which in this description text is called an office computer 105. The office computer 105 is communicatively connected to the computerised unit 102, also called the laboratory computer 102, by means of a communication link 107. The communication link 107 can for example be realised as a wired communication link, such as a network connection, or a wireless communication link using for example IR technique or bluetooth technique. The office computer 105 is arranged to access information about a study, e.g. an ongoing study or a completed study, via the laboratory computer 102. Each of the sample taking devices 100 has preferably a unique identity, e.g. an identification number or name, whereby an experimenter by means of the coinputerised unit 102 or a PDA 104 can establish a communication link with a specific sample taking device 100 and thus retrieve status information about the experiment. The experimenter can for example retrieve information about how many samples that have been taken, when they have been taken, the volume of each of the taken samples and how many samples that are left to be taken. According to an embodiment of the invention, the specimen taking system 10 and its functions are automatically controlled by means of computer program software being executed on a control data processing system. Specific test schemes are also controlled by such a computer program product, for example specimen taking dependent on a time schedule for collecting samples or specimen from the test object. The control data processing system may be a dedicated control data processor, a computerised unit 102, 104 or a sample taking device 100 set up with a suitable control program. The user can through a user interface define the specimen taking procedure and different specimen taking parameters, for example by defining a selectable number of specimens to be taken with a selectable time interval or at specific points in time. As mentioned above, there is also functional means configured for storing information on taken specimens, such as time and specimen identity. The computer program product comprises program code portions adapted to direct a data processing system to perform the steps of the inventive method or control the movements of the system components as described in this description. The computer program product preferably comprises a carrier in the shape of a storage medium, such as a diskette or CD or the like, for storing the inventive computer program portions.
Taking of samples Embodiments of an inventive specimen taking device will be described below with reference to the Figs. 2a-2f. In the figures, the components of the specimen talcing device and the laboratory animal are for the sake of clarity drawn apart from each other, but as mentioned above, the components of the specimen taking device is preferably arranged as an integrated unit which is portable, i.e. the integrated unit can easily be carrie by the test object, and removably attached to the test object. A schematic first embodiment of a specimen taking device or sample taking device will now be described with reference to Fig.2a. The embodiment of the specimen taking apparatus in accordance with the invention comprises a hollow specimen collector 120 comprising a proximal end 122 with an inlet and configured to be connectable to an outlet 132 of a test site or a test location 130 of a test object 1 and a distal end 124 having an outlet, whereby a taken sample from the test site 130 can be transported from the inlet of the proximal end 122 to the outlet of the distal end 124 through the specimen collector 120. A sample can then by means of the natural flow rate at the outlet of the test site 130 be transported from the outlet 132 of the test site 130 through the specimen collector 120 and discharged to a test tube 140. In for example the case of talcing urine or bile samples, the proximal end of the specimen collector is preferably introduced into the urethra or the bile duct of the test object, respectively. In such cases, the samples can be taken at predetermined time points at an outlet from the test site using the natural rate of the outflow. For example, the samples can be taken at time points defined by a constant time interval, which can entail that the volume of the taken samples fluctuates between the samples. Further, if it is desirable to take samples having the same volume, a pressure sensor can be arranged at the outlet of the test site and arranged to measure the pressure at the outlet. The sensor can be connected to a control unit arranged to control the sample taking. Thus the sensor can be used to determined the time period during which the sample is taken in order to achieve a desired sample volume. Furthermore, if it desirable to take samples having the same volume during a constant time period and at a constant time interval, the sensor can be connected to a pumping means. The pumping means can be arranged at the specimen collector between the test site and the test tube. This pumping means is preferably controlled or regulated by means of the sensor. The measured pressure can be used to determined the flow rate at the outlet, which information can be used as an input to the pumping means. Then the pumping means can be arranged to change the flow rate to a desired flow rate in order to take the desired sample volume at a desired time point and during a desired time period. In many cases it is desirable to study the interaction between a specific test solution and a test site, e.g. for example the interaction between a pharmaceutical and an organ or a tissue structure. It can for example be desirable to study the ability of an organ to take up or break down a substance comprised in a supplied test solution or the rate of the uptake or breakdown. In such cases it is often desirable to have a controllable flow rate into and out from the test site. A schematic second embodiment of a specimen taking device or sample taking device will now be described with reference to Fig. 2b. This embodiment of the specimen taking apparatus in accordance with the invention comprises in addition to the hollow specimen collector 120 and the test tube 140 as described above with reference to Fig. 2a, a test solution source 150 comprising a test solution 152 which can be supplied to an inlet 134 of the test site 130 via a hollow solution supplier 160. The test solution source 150 can for example be realised as an air-proof container or a receptacle having an air-tight sealing. The solution supplier 160 comprises a proximal end 162 with an outlet, which proximal end 162 is connectable to an inlet 134 of the test site 130 of the test object 1, and a distal end 164 having an inlet, which distal end 164 is connectable to the solution source 150. Thus, a test solution 152 can be transported from the inlet of the distal end 164 to the outlet of the proximal end 162 through the solution supplier 160 by means of for example a pumping means 166 such as a peristaltic pump. According to this embodiment of the invention, the pumping means 160 is able to provide a desired flow rate of the supplied test solution needed for the experiment or study. In the case of for example dermatological studies, a dialysis membrane, e.g. a tubing having an inlet, an outlet in and a permeable wall, can be percutaneously arranged under the skin of a test object. A test solution, e.g. a dialysate, can be supplied to the inlet of the tubing and can further be arranged to flow to the outlet of the tubing, whereby the test solution will penetrate the permeable wall and mix with the body fluid surrounding the tubing when it is arranged at the test site. Further, the body fluid surrounding the tubing will penetrate the permeable wall and mix with the test solution flowing inside of the tubing. Thus at the outlet of the tubing a sample, i.e. a mixture of test solution and body fluid, can be collected. In case of dermatological studies, the desired flow rate of the supplied test solution should be low enough for the supplied test solution to penetrate the permeable wall of the tubing and thus the desired flow rate should be low enough to provide samples that are representative for the concentration of the test solution in the test site, i.e. to provide samples that have a concentration of the test solution that corresponds to the concentration of the test solution in the test site. For example, a suitable flow rate can be in the range of 1 microlitre per minute. Thus it will take approximately 20 minutes to get a total sample volume in a test tube of approximately 20 microlitres. However, if the flow rate of the supplied test solution is too high the concentration of the test solution in the taken samples will be lesser than the concentration in the cells and thus a non- representative sample is taken. In Fig. 2c a schematic third embodiment of the inventive sample taking device is shown. In this embodiment, the flow rate of the supplied test solution 152 is controlled by means of an overpressure in the solution source 150, i.e. the pressure in the solution source 150 is higher than the pressure on the outside of the solution source 150. The over pressure is achieved by supplying a preselected or predetermined volume of a gas or a gas mixture 172 to the solution source 150 by means of a gas supplier 170. The gas supplier 170 can for example be realised as a syringe or a container comprising the gas or gas mixture. If for example a gas volume of 1 millilitres is supplied to a solution source having a total volume of 1 millilitre and comprising 200 microlitres of a test solution, the pressure in the solution source will increase with 20 %. This increased pressure will result in a variation of the achieved flow rate of 20 % which in some cases is too high and a not acceptable flow rate variation. If on the other hand a gas volume of 5 millilitres is supplied to the solution source having a total volume of 1 millilitre and comprising 200 microlitres of a test solution, the pressure will increase with 4 % and a flow rate variation of 4 % is achieved. Thus to achieve an acceptable flow rate variation, e.g. in the range of 4 - 5 %, a relatively large volume of gas, as compared to the volume of the solution, has to be supplied to the solution source. A schematic fourth embodiment of the inventive sample taking device is shown in Fig.2d. In this embodiment the test solution source 150 is configured as a tube or a tubing and comprises a proximal end 154 having an outlet and a distal end 156 having an inlet. Further, the proximal end 154 of the solution source 150 is connectable to the distal end 164 of the solution supplier 160. Furthermore, in the cavity defined by the inner walls of the solution source 150 between the proximal end 154 and the distal end 156 the test solution 152 is comprised. The distal end 156 of the solution source 150 is configured to be connected to the outlet of a gas supplier 170 comprising a gas or a gas mixture 172 having an over pressure, i.e. the pressure in the gas source 170 is higher than the pressure on the outside of the gas source 170. In this embodiment the gas supplier 170 can be realised as an air-proof container or reservoir having an air-tight sealing. As mentioned above the solution source 150 is configured as a tube or tubing, which can be manufactured of Teflon® or another suitable plastic or plastic-like material that does not or minimally affect the test solution negatively. Further, the solution source 150 is preferably manufacture of a flexible material, i.e. of a material that can be bent or rotated easily without breaking. 5 Furthermore, the inner diameter of the solution source 150 is in the range of 0,5 - 3 millimetres, preferably approximately 1 millimetre. However, it should be understood that the inner diameter of the solution source 150 can be varied dependent on inter alia the desired volume and flow rate of the test solution to be supplied. Usually, it is desirable to provide an inner diameter of the solution source 150 that is much larger than the inner
10 diameter of the solution supplier 160. If for example the inner diameter of the solution supplier 160 is in the range of 0,1 millimetre or less, a suitable inner diameter of the solution source 150 is approximately 1 millimetre. The solution source 150 is further configured in such a way that the test solution 152 is provided as a liquid column in the flexible solution source 150.According to the
15 embodiment shown in Fig. 2d, the solution source 150 can be helical or provided with a helical-like shape. By this arrangement and due to the capillary force, the solution supplier 160 and solution source 150 can be bent or turned without risking that the gas supplied to the solution source 150 from the gas supplier 170 passes by parts of the test solution 152 in the solution source 150. Thus, the laboratory animal can move freely and the risk of gas
20 bubbles in the test solution 152 is avoided or reduced. According to Fig. 2d, the solution source 150 and the gas source 170 are vertically arranged along their longitudinal axis, but it should be understood that they can be arranged in any direction. Fig. 2e shows a schematic fifth embodiment of the inventive sample taking device.
25 According to this embodiment, an outlet of a second gas source 180 comprising a gas or gas mixture 182 is connected to an inlet of a first gas source 170 by means of a tube or a tubing 192. Preferably, the gas pressure p2 in the second gas reservoir 180 is larger than the gas pressure pi in the first gas reservoir 170, i.e. p2 > pi , entailing a gas flow from the second gas reservoir 180 to the first gas reservoir 170. Further, a gas flow control means
30 190 is arranged at the tubing 190, which gas flow control means 190 is configured to control or regulate the gas flow from the second gas source 180 to the first gas source 170. The gas flow control means 190 can for example comprise or be realised as a valve having an open position, which enables a gas flow between the gas sources 170, 180, and a closed position, which prevents the gas flow. The gas flow control means 190 can also be arranged to have one or several intermediate positions, whereby the flow rate of the gas can be varied. In another embodiment, a clip or a pliers, e.g. a forceps, is realising the gas flow control means 190, whereby the gas flow can be regulated by means of the clip or the pliers. In this fifth embodiment of the sample taking device, a sensor 174 can be arranged at the first gas reservoir 170. The sensor 174 is arranged to detect or register the pressure in the first gas reservoir 170. Further, information about the pressure in the first gas source 170 can then be used as an input to the gas flow control means 190, whereby the gas flow control means 190 can be configured to control the gas flow from the second gas source 180 to the first gas source 170 dependent on the pressure in the first gas source 170. This can be an essential feature of the gas flow control means 190 since the pressure in the first gas source 170 determines the flow rate of the test solution 152 comprised in the test solution source 150. As a general rule, a higher pressure in the first gas source 170 entails a higher flow of the test solution. Further, the flow rate of the test solution can be determined if one knows the pressure in and the volume of the first gas source 170. A schematic sixth embodiment of the inventive sample taking device will be described with reference to Fig.2f. In this embodiment, a pumping means 166 is arranged at the solution supplier 160 between a solution source 150 and a test site 130 of the laboratory animal. The pumping means 166 is further arranged to control the flow rate of a test solution 152 from the solution source 150 to the test site 130, and can be realised as a liquid pump, a diaphragm pump or a membrane pump. Further, a first gas source 170 comprising a sensor 174 is, by means of a tubing 176 and for example a T-connection, connected to the solution supplier 160 between the pumping means 166 and the test site 130. The sensor 174 is arranged to detect or measure the pressure in the gas source 170. Furthermore, the sensor 174 is communicatively connected or coupled to the pumping means 166, whereby the functioning of the pumping means 166 can be controlled dependent on the measured pressure in the first gas source 170. In one embodiment of the invention, the pumping means 166 is arranged to pump a test solution 152 from the test solution source 150 through the solution supplier 160 and towards the test site 130. During the pumping procedure, the test solution 152 will also flow into the tubing 176 towards the first gas source 170. To avoid that the test solution 152 reaches the first gas source 170, the tubing 176 is able to comprise a sufficient volume. The volume of the tubing 176 is for example equal to or almost equal to the volume of the gas source 170. Preferably, the volume of the tubing 176 is such that when the sensor 174 registers a maximum pressure in the gas source 170, the test solution 152 in the tubing 176 has not reached the gas source 170. Then, the pumping means 166 is turned off and the overpressure in the gas source 170 will cause the test solution comprised in the tubing 176 to flow towards the test site 130. Further, the overpressure in the gas source 170 will be reduced and finally the pressure in the gas source 170 will be equal to a minimum pressure. This minimum pressure will be registered by the sensor 174, which will turn on the pumping means 166, and the procedure described above will be repeated. As shown in Fig. 2f, the solution source 150 can according to an embodiment of the invention be connected to or integrated with a reservoir 150', which can comprise a test solution 152' or be refillable with a test solution 152' . In the described embodiments, the solution source and the tubing is preferably manufactured of a flexible material and configured to be helical or to have a helical-like shape. By this configuration and due to the capillary force, the solution supplier 160, the solution source 150 and the tubing 176 can be bent or turned without risking that the supplied gas passes by parts of the test solution and is supplied to the test site. Thus, the laboratory animal can move freely and the risk of supplying gas bubbles to the test site is avoided.
Taking of blood samples Embodiments of an inventive specimen taking device which can be used for taking blood samples will be described below with reference to the Figs. 3-6. In Fig. 3, the components of the specimen taking device 300 and the laboratory animal 301 are for the sake of clarity drawn apart from each other. However as mentioned above, the components of the specimen taking device is preferably arranged as an integrated unit which is portable and removably attached to the test object. An embodiment of a specimen taking device 300 for taking of e.g. blood samples is schematically shown in Fig. 3. In the figure an proximal end 322 of a first part 320a of a sample collector 320 having a lumen is inserted into a test site, e.g. a blood vessel 310, of a laboratory animal 301 by means of a mini-invasive technique using e.g. an introducer (not shown) or by surgical cut-down. A distal end 324 of the first part 320a of the sample collector 320 is connected to a flow control means 330, for example realised as a valve. The flow control means 330 is configured to have at least two positions, a first position providing a fluid flow between the distal end 324 of the first part 320a and a proximal end 325 of a second part 320b of the sample collector 320, while the fluid flow between the distal end 324 and a proximal end 327 of a third part 320c of the sample collector 320 is blocked. The second position of the valve 330 provides a fluid flow between the distal end 324 of the first part 320a and the proximal end 327 of the third part 320c of the sample collector 320, while blocking fluid flow between the distal end 324 and the proximal end 325 of the second part 320b of the sample collector 320. Further, the second part 320b of the sample collector 320 is connected to a solution source 350 via a pumping means 360, e.g. realised as a peristaltic pump or the like. The second part 320b is configured to have a distal opening or inlet in a distal end 326, whereby a rinsing solution 352, e.g. comprising sodium chloride, comprised in the solution source 350 can be transported in the second part 320b from the inlet to a proximal opening or outlet of the proximal end 325, by means of the pumping means 360. If the valve 330 is in its first position the rinsing solution 352 can be transported and supplied to the laboratory animal 301 via the first part 320a of the sample collector. If on the other hand the valve 330 is in its second position the rinsing solution 352 can be transported to a test tube 340 or a not shown waste container, via a distal opening in the distal end 328 of the third part 320c. The pumping means 360 is arranged to provide a flow of a fluid, e.g. blood, from the laboratory animal 301 into the first part 320a of the sample collector 320 via an inlet in a proximal end 322 of the first part 320a. If the valve 330 is in its first position, blood can be transported in a lumen of the sample collector 320 to the second part 320b. When a volume of the blood has passed the valve 330 and is located in the second part 320b of the sample collector 320, the valve 330 can be switched to be in its second position. The volume of the blood comprised in the second part 320b constitutes the blood sample and can be transported to the third part 320c by means of the pumping means 360. Further, the taken blood sample can be supplied to a test tube 340, via a distal opening or outlet in a distal end 328 of the third part 320c, by means of the pumping means 360. According to an embodiment, the method of taking a blood sample comprised the steps of (cf. Fig. 4):
400 filling the lumens of the sample collector 320 with a rinsing solution which is not harmful to the laboratory animal, e.g. a solution comprising sodium chloride;
401 introducing a proximal end 322 of the first part 320a into a test site, e.g. a blood vessel, of the laboratory animal;
402 setting the flow control means 330 in a first position, in which position the connection between the first part 320a and the second part 320b is open; 403 extracting blood from the laboratory animal 301 to the second part 320b of the sample collector 320 via the inlet of the proximal end 322 of the first part 320a, whereby the volume blood comprised in the second part 320b constitutes the blood sample; 404 setting the flow control means 330 in a second position, in which position the connection between the second part 320b and the third part 320c is open;
405 moving the distal end 328 of the third part 320c to a location at a waste container;
406 transporting the blood sample to an outlet in a distal end 328 of the third part 320c of the sample collector 320, whereby the rinsing solution comprised in the lumen of the third part 320c is supplied to the waste container;
407 moving the distal end 328 of the third part 320c to a test tube 340;
408 supplying the blood sample to the test tube 340;
409 moving the distal end 328 of the third part 320c to the waste container;
410 transporting rinsing solution from the solution source 350 to the waste container; 411 setting the flow control means 330 in the first position;
412 transporting blood comprised in the first part 320a back to the laboratory animal and supplying a volume of the rinsing solution 352 to the laboratory animal 301, which volume is approximately equal to the volume of the taken blood sample;
413 if more samples are to be taken, wait a predetermined time and repeat from step 403; else
414 sample taking is completed. Thus, in step 400 a rinsing solution not harmful to the laboratory animal 301 is supplied to the lumens of the sample collector 320. The rinsing solution can for example comprise a sterile sodium chloride solution or a Ringer's acetate solution. In step 401, the proximal end 322 of the first part 320a is introduced into a blood vessel of the laboratory animal. The flow control means 330 is in step 402 set in a first position enabling fluid flow between the first part 320a and the second part 320b of the sample collector 320, while prohibiting fluid flow between the first part 320a and the third part 320c. Blood is then in step 403 extracted from the laboratory animal 301 to the second part 320b of the sample collector 320 via the inlet of the proximal end 322 of the first part 320a, whereby the volume blood comprised in the second part 320b constitutes the blood sample. The flow control means 330 is in step 404 set in a second position enabling fluid flow between the second part 320b and the third part 320c of the sample collector 320, while prohibiting fluid flow between the first part 320a and the second part 320b. In step 405 the distal end 328 of the third part 320c is moved to a location at a waste container (not shown). The blood sample comprised in the second part 320b is then in step 406 transported to an outlet in a distal end 328 of the third part 320c of the sample collector 320, whereby the rinsing solution comprised in the lumen of the third part 320c is supplied to the waste container. Thus the taken sample is comprised in the third part 320c from the opening in the distal end 328 of the third part 320c towards the flow control means 330. The distal end 328 of the third part 320c is in step 407 moved to be located at a test tube 340 in such a way that the blood sample can be supplied to the test tube 340 in step 408. The distal end 328 of the third part 320c is then in step 409 moved to a location at the waste container in such a way that a volume of the rinsing solution 352 in step 410 can be transported from the solution source 350 to the waste container via the second 320b and third 320c parts of the sample collector 320. In step 411, the flow control means 330 is set in the first position, whereby the blood comprised in the first part 320a and a volume of the rinsing solution 352 in step 412 can be supplied to the laboratory animal 301. The volume of the rinsing solution supplied to the animal is preferably approximately equal to the volume of the taken blood sample in order to restore the fluid balance of the laboratory animal. Then in step 413, if a further sample is to be taken the steps are repeated from step 403 after a preset time period otherwise the sample taking procedure is ended in step 414. According to another embodiment of the method, an air bubble can be used to separate the extracted sample from the rinsing solution comprised in the sample collector 320. Such a method can comprise the steps of (cf. Fig. 5):
500 filling the lumens of the sample collector 320 with a rinsing solution which is not harmful to the laboratory animal 301, e.g. a solution comprising sodium chloride;
501 introducing the proximal end 322 of the first part 320a into a test site, e.g. a blood vessel 310, of the laboratory animal;
502 setting the flow control means 330 in a second position, in which position the connection between the second part 320b and the third part 320c is open;
503 actuating the pumping means 360 in such a way that a first air bubble is sucked into the proximal end 325 of the second part 320b via the opening in the distal end 328 of the third part 320c;
504 setting the flow control means 330 in the first position, in which position the connection between the first part 320a and the second part 320b is open; 505 extracting blood from the laboratory animal 301, via the opening in the proximal end 322 of the first part 320a, to a distal end 324 of the first part 320a adjacent to the flow control means 330;
506 setting the flow control means 330 in the second position; 507 actuating the pumping means 360 in such a way that a second air bubble is sucked into the proximal end 325 of the second part 320b via the distal end 328 of the third part 320c;
508 setting the flow control means 330 in the first position;
509 transporting blood comprised in the first part 320a to the second part 320b of the sample collector 320, whereby the volume blood comprised in the second part 320b constitutes the blood sample;
510 setting the flow control means 330 in the second position;
511 transporting the blood sample to an outlet in the distal end 328 of the third part 320c of the sample collector 320; 512 moving the distal end 328 of the third part 320c to a test tube 340;
513 supplying the blood sample to the test tube 340;
514 moving the distal end 328 of the third part 320c to a waste container;
515 supplying rinsing solution 352 from the solution source 350 to the waste container via the second 320b and third 320c parts, whereby the air bubbles are removed and the second 320b and third 320c parts are rinsed;
516 setting the flow control means 330 in the first position;
517 transporting the blood comprised in the first part 320a back to the laboratory animal 301 and supplying a volume of the rinsing solution 352 from the solution source 350 to the animal 301, which volume is approximately equal to the volume of the taken blood sample;
518 if more samples are to be taken, wait a predetermined time and repeat from step 502; else
519 sample taking is completed. In step 500 a rinsing solution not harmful to the laboratory animal 301 is supplied to the lumens of the sample collector 320. As mentioned above the rinsmg solution can for example comprise a sodium chloride solution or a Ringer's acetate solution. Confer Fig. 6a showing the contents of the three parts 320a - 320c after step 500. In step 501, the proximal end 322 of the first part 320a is introduced into a test site, e.g. a blood vessel, of the laboratory animal. The flow control means 330 is in step 503 set in the second position, i.e. the position enabling a fluid flow between the second part 320b and the third part 320c of the sample collector 320, while disabling a fluid flow between the first part 320a and the second part 320b of the sample collector 320. The pumping means 360 is in step 502 actuated in such a way that a first air bubble is sucked into the proximal end 325 of the second part 320b via the opening in the distal end 328 of the third part 320c. This first air bubble can be detected by a sensor means (not shown) arranged at the pumping means 360 whereby the pumping means 360 can be controlled to stop pumping fluid in the direction towards the solution source 350. Confer Fig.6b showing the contents of the three parts 320a - 320c after step 503. However, it should be understood that an air bubble or a gas bubble can be supplied to the second part 320b by means of an air inlet or a gas inlet arranged at for example the flow control means. In step 504, the flow control means 330 is set in the first position enabling a fluid flow between the first part 320a and the second part 320b, while preventing a fluid flow between the first part 320a and the third part 320c. Blood is then in step 505 extracted from the laboratory animal 301 to a distal end 324 of the first part 320a via the opening in the proximal end 322 of the first part 320a. Further, the volume of the extracted blood is such that the distal end 324 of the first part 320a, which distal end 324 is adjacent to the flow control means 330, comprises blood. Confer Fig. 6c showing the contents of the three parts 320a - 320c after step 505. However, it should be understood that blood can be extracted into the second part 320b, but the blood will then be mixed with the rinsing solution comprised in the second part 320b. Such a mixture of blood and rinsing solution is sometimes called waste solution. In step 506 the flow control means 330 is set in the second position and in step 507 the pumping means 360 is actuated in such a way that a second air bubble is sucked into the proximal end 325 of the second part 320b via the third part 320c. Confer Fig. 6d showing the contents of the three parts 320a- 320c after step 507. The flow control means 330 is then in step 508 set in the first position and the blood comprised in the first part 320a is in step 509 transported to the second part 320b of the sample collector 320. The volume blood comprised in the second part 320b constitutes the blood sample. Confer Fig. 6e showing the contents of the three parts 320a - 320c after step 509. In step 510 the flow control means 330 is set in the second position and in step 511 the blood sample is transported to an outlet in the distal end 328 of the third part 320c of the sample collector 320. Thus, the blood sample is located in the third part 320c from the outlet in the distal end 328 of the third part 320c towards the flow control means 330. Confer Fig. 6f showing the contents of the three parts 320a - 320c after step 511. If the distal end 328 of the third part 320c is not located at a test tube 340, the distal end 328 of the third part 320c is in step 512 moved to a test tube 340, whereby the blood sample in step 513 can be supplied to the test tube 340 by means of the pumping means 360. Confer Fig. 6g showing the contents of the three parts 320a- 320c after step 513. After delivery of the blood sample, the distal end 328 of the third part 320c is in step 514 moved to a waste container and in step 515 rinsing solution 352 is supplied from the solution source 350 to the waste container via the second 320b and third 320c parts. Thus, the air bubbles are removed and the second 320b and third 320c parts are rinsed. Confer Fig. 6h showing the contents of the three parts 320a - 320c after step 515. In step 516 the flow control means 330 is set in the first position and in step 517 the blood comprised in the first part 320a is transported back to the laboratory animal 301. Further, a volume of the rinsing solution 352 is supplied from the solution source 350 to the animal 301, which volume preferably is approximately equal to the volume of the taken blood sample to restore the fluid balance of the animal. Confer Fig. 6i showing the contents of the three parts 320a- 320c after step 517. Then in step 518, if a further sample is to be taken the steps are repeated after a preset time period from step 502 otherwise the sample taking procedure is ended in step 519. According to an embodiment of the invention, the length of the second part 320b between the flow control means 330 and the pumping means 360 is long enough to comprise a volume corresponding to the sum of volume of a solution comprised in the first part 320a, the volume of a the waste solution i.e. a the solution between the first and second air bubble, the volume of the air bubbles and the volume of the fluid sample. It should be understood that the some of the steps described above with reference to the Figs. 4 and 5 can be performed in a different order and that the flow rate can be different in different parts of the sample collector. In some studies for example, it is desirable that the flow rate to and/or from the laboratory animal is lower than the flow rate to the test tube or waste container. Embodiments of the sample taking device as described with reference to Fig. 3 can further be used in pharmacokinetic studies. Thus, an embodiment of the sample taking device comprises further a test solution source having a test solution which can be supplied to the laboratory animal via the second 320b and first 320a parts of the sample collector 320 as described above. In such an embodiment the second part 320b can comprise two branches in its distal part, whereby rinsing solution can be supplied via a first branch and test solution via a second branch. The test solution comprising e.g. pharmaceutical compounds or a pharmaceutical substance, is in most studies supplied once to the laboratory animal and the sample taking procedure as described above starts after a preselected period of time. Another embodiment of a sample taking device for pharmacokinetic studies is configured as a combination of the sample taking device as described with reference to Fig. 3 and one of the sample taking devices as described with reference to Figs. 2b - 2f. In such a combination, the test solution is supplied to the laboratory animal via the solution supplier by means of a pumping means as described above with reference to Figs. 2b - 2f. Further, the sample taking procedure is performed using components of the sample taking device according to Fig. 3 and the method according to Fig. 4 or 5.
Sample taking device An embodiment of a sample taking device described above will now be described in more detail with reference to Figs. 7a-7e. The sample taking device 100, 300 can further comprise a support plate 710 having a first side 711 and an opposite second side 712. In an embodiment, the support plate 710 has a rectangular shape and the first and second sides 711, 712 have surfaces that are approximately parallel. At the first side 711 of the support plate 710, a nut 713, e.g. a ball nut, is mounted in a bearing 714, such as a ball bearing, and a first cog wheel or tooth wheel 715 is arranged at the ball nut 713. For example, the first tooth wheel 715 is pressed on to the ball nut 713. Thus, when the first tooth wheel 715 is rotated, the ball nut 713 will rotate. The ball nut 713 is further arranged at a screwed rod or bar 716, such as a ball nut screw, which will be moved along its longitudinal axis when the ball nut 713 is rotated. Since the ball nut 713 is mounted in the bearing 714, the ball nut 713 will not be moved along its longitudinal axis but only rotated around its longitudinal axis, implying that the ball nut screw 716 will be moved along its longitudinal axis and not rotated. The direction of the movement depends on the direction of the rotation. At the first side 711 of the support plate 710 is a second cog wheel or tooth wheel
717 is arranged at an axle 718 or the like, which second tooth wheel 717 is arranged to engage the first tooth wheel 715. Furthermore, the second tooth wheel 717 is connected to a movement control means 720, which is realised as a stepping motor, but can for example be realised as a servo-motor or another suitable drive unit. At the first side 711 is further a bearing 708, such as a linear bearing, fixedly attached to the support plate 710 and arranged at a linear axle 719 in such a way that the linear axle 719 can be moved along its longitudinal axis, cf. Fig. 7b. First ends of the ball nut screw 716 and the linear axle 719 are rigidly attached to a first fixing plate 721 and arranged approximately parallel to each other. Thus, when the second tooth wheel 717 is rotated by means of the stepping motor 720, the first tooth wheel 715 is rotated and the ball nut screw 716 is moved along its longitudinal axis. Further the linear axle 719 is correspondingly moved along its longitudinal axis due to the fixing plate 721. According to the embodiment shown in Figs. 7a-7d, the movement control means
720 is arranged at the second side 712 of the support plate 710, at which second side 712 a housing 730 is arranged. The housing 730 is arranged turnable around its longitudinal axis and configured to uphold a fraction assembler 740. The fraction assembler 740 is configured to be removably attached to the housing 730 of the support plate 710 of the sample taking device. The fraction assembler 740 is further configured to comprise one or several test tubes (not shown) for storing samples and waste solution. It should be understood that the waste container mentioned above can be realised as one of the test tubes comprised in the fraction assembler. The first fixing plate 721 comprises a delivery means 750, having a lumen, a proximal and a distal end openings. The delivery means is according to an embodiment stiff or rigid and is for example realised as a hollow needle. The delivery means 750 is further movable along its longitudinal axis through a hole 709 in the support plate 710. The distal end 124, 328 of the specimen collector 120, 320 is further connectable to the proximal end 752 of the delivery means 750. Further, the distal end 754 of the delivery means 750 is devised to deliver a taken specimen or a waste solution to a test tube 140, 340 or a waste container, respectively, comprised in the fraction assembler 740. Thus, a sample or a waste solution comprised in the lumen of the sample collector 120, 320 can be supplied to a test tube 140, 340 or a waste container via the lumen and the distal end opening of the delivery means 750. However, according to another embodiment of the invention, the delivery means is configured as a guiding means for the specimen collector, such as an introducer sheath. According to this embodiment the distal end of the sample collector is inserted through the delivery means such that a distal tip of the sample collector is positioned distally of the distal end opening of the delivery means. As mentioned above, the delivery means 750 is fixedly arranged at the first fixing plate 721 which is fixedly attached to the linear axle 719 and to the ball nut screw 716. Further, the linear axle 719 and the ball nut screw 716 are movably arranged at the support plate 710 such that they can be moved along their longitudinal axis through holes in the support plate 710. Thus, the delivery means 750 is arranged to be movable along its longitudinal axis and the control means 720 is arranged to control the movement of the delivery means 750 and to control the position of the delivery means 750. According to an embodiment of the invention, the control means 720 is realised as a stepping motor 720 and a power source (not shown) is arranged to supply electrical pulses to the stepping motor 720. The power source can be realised as a battery, e.g. a rechargeable battery. The stepping motor 720 is arranged to provide a step-by-step movement of the delivery means 750 and in some studies a step length of approximately 1 millimetre is suitable. A sensor 722 is further communicatively connected to the stepping motor 720, which sensor 722 detects the position of the delivery means 750. The sensor 722 can for example be realised as a micro switch. By means of the stepping motor 720, the delivery means 750 can be moved between a first position and a second position. In the first position, the delivery means 750 is retracted and in the second position the delivery means 750 is extended. If a test tube or a waste container comprised in the fraction assembler 740 is arranged at a location suitable for delivery of a solution, i.e. the longitudinal axis of the test tube or waste container approximately coincide with the longitudinal axis of the delivery means 750, and the delivery means 750 is in the first position, the distal tip of the delivery means 750 is located outside of the test tube 140, 340 or waste container. In the second position, the distal tip of the delivery means 750 is inserted into the test tube 140, 340 or waste container and located close to the inner bottom thereof. In this second position the delivery of the sample or the waste solution starts. However, since it often is desirable to avoid contamination of the delivered sample or waste solution on the outer surface of the delivery means 750, the delivery means 750 is moved stepwise during the delivery of the solution from the second position towards the first position. This stepwise movement of the delivery means 750 continues until the total volume of the solution has been delivered. When the delivery of the sample is completed the delivery means 750 is retracted to its first position. In some studies it is desirable to avoid air bubbles in the sample comprised in the test tube. To avoid or minimise the risk air bubbles, the movement of the delivery means is preferably controlled in such a way that the distance between the tip of the delivery means and the surface of the delivered sample is shorter than the distance between the outer surface of the delivery means and the inner wall of the test tube. Further, second ends of the ball nut screw 716 and the linear axle 719, located on the second side 712 of the support plate 710, are rigidly attached to a second fixing plate 723, cf. Fig. 7d. When the delivery means 750 is moved from its second position towards the first position, the second fixing plate 723 is moved towards the second side 712 of the support plate 710 and the sensor 722 will detect the second fixing plate 723. Thus the sensor 722 will indicate that the delivery means 750 is in its first position and the movement of the delivery means 750 will stop. Further, when the delivery means 750 is moved from its second position to its first position, the second fixing plate 723 is moved towards the housing 730 of the support plate 710. According to an embodiment, the housing 730 has a saw-toothed shape and the fixing plate 730 comprises a pin 724, cf. Figs. 7a and 7d. The pin 724 and the saw-toothed shape of the housing 730 is further configured in such a way that the pin 724, when moved towards the support plate 710, will engage the housing 730 resulting in a rotation of the housing 730. The fraction assembler 740 is arrangeable in the housing 730 in such a way that it will rotate around its longitudinal axis together with the housing 730. Preferably, the rotation of the fraction assembler 740 corresponds to the rotation of the housing 730. The distance between the teeth corresponds approximately to the distance between two test tubes comprised in the fraction assembler 740, implying that after the rotation a new test tube will be located in a position suitable for delivery of a sample. Thus the fraction assembler 740 can be rotated when the delivery means 750 is in the first position after the delivery of a first sample to a first test tube, whereby a second test tube is moved to a position in which the deliver means 750 is capable of delivering a second sample to the second test tube. If the rotation of the housing provided by the control means is not sufficient, magnets can for example be arranged to rotate the housing in place. According to an embodiment of a housing shown in Fig. 7e, the housing 730 comprises a set of magnets 731, which are evenly distributed such that each magnet 731 corresponds to a position of a test tube comprised in an attached fraction assembler. A magnet 726 is further arranged at the second side 712 of the support plate 710 and outside the housing 730, cf. Fig. 7c and 7d. The magnets 731 are preferably permanent magnets having a magnetic pole outwards that is opposite of an inwards magnetic pole of the magnet 726 arranged at the support plate 710. If the housing 730, by means of the stepping motor 720 and the pin 724 of the second fixing plate 723, is rotated, the magnet 731 closest to the magnet 726 and the magnet 726 will rotate the housing 730 to a position in which the magnet 731 and the magnet 726 of the support plate 710 are facing each other. Thus, if a fraction assembler 740 is attached to the housing 730, the fraction assembler 740 will be rotated as well and the longitudinal axis of a test tube will be approximately coincident with the longitudinal axis of the delivery means 750. The control means 720 can further comprise a second sensor 725 configured to operate as a revolution counter. In embodiments of the invention, the sensor 725 is realised as a micro switch. In such an embodiment, the outer surface of housing 730 can comprise a small cavity or a protrusion, or the like, which is arranged to be detected once per revolution by the sensor 725. Figs 8a - 8d show schematically a fraction assembler 740 having an approximately cylindrical shape. In the fraction assembler 740 a number of openings 741 for test tubes and a centrally located recess or depression 742 for mounting at a projection or protrusion 732 of a housing 730 are provided, cf. also Fig 7e. That is the recess 742 is functioning as a female connector and the protrusion 732 as a male connector. However, another connection between the fraction assembler and the housing is also possible. In an embodiment of the invention, the friction between the surface of the recess and the surface of the protrusion is not sufficient to hold the fraction assembler. In such an embodiment the fraction assembler 740 can held in position at the housing 730 by means of a magnet 743 at the recess 742 and a magnet 733 at the protrusion 732. Further, in order to correctly position the fraction assembler 740 in the housing, the fraction assembler can be provided with a set of through holes 744 having a configuration corresponding to a configuration of a set of through holes 734 in the housing 730 and the support plate, whereby rods or the like can be inserted through the holes. The holes can have different configuration entailing that only a fraction assembler having a special configuration of holes can be attached to a certain housing. Furthermore, to fixate test tubes 140, 340 in the fraction assembler 740, a part of the fraction assembler 740 can be provided with a slot or a slit 745 in an outer surface thereof, as shown in Fig. 8d. The slot 745 is arranged along the circumference of the outer surface of the fraction assembler 740. Further a set of through holes 746 are provided in the slit 745, which holes 746 are evenly distributed in the slit 745 and the position of each of the holes 746 corresponds to the position of a hole 741 for a test tube. An O-ring or an elastic band (not shown) can be arranged in the slit 745 to fasten the test tubes when positioned in the fraction assembler. This fastening of the test tubes is accomplished due to the set of holes 746, since the holes 746 provide the elastic band to bear against a part of the outer surface of the test tubes. In an embodiment of the fraction assembler, a hole (not shown) can be arranged in each opening 741 for a test tube. The hole has a diameter that is smaller than the diameter of the opening 741. When removing the test tubes from the fraction assembler a plate having pins, or the like, protruding from the plate. The pins are arranged to be inserted into the holes of the openings 741 to push up the test tubes comprised in the fraction assembler. Just before the start of the sample taking procedure, the fraction assembler according to embodiments of the invention can be loaded with test tubes which are cooled down to a desired temperature in order to better preserve the taken samples. Alternatively, the fraction assembler can be filled with an internal medium, such a water, and cooled to for example approximately -1 degree Celsius before the start of the sample taking procedure, whereby the water freezes. The melting heat can then be used to cool the test tube and thus to preserve the taken samples. The fraction assembler is according to an embodiment comprised in an insulating covering or housing, such as a Frigolit® housing, during the sample taking procedure in order to maintain the temperature of the fraction assembler. In an embodiment of the invention, the sample taking device has diametrical dimensions of approximately 45x35x80 millimetres (width, depth, height). However, it should be understood that the dimensions can be varied dependent on for example the size of the test object or the kind of study to perform.
The components of the sample taking device is conveniently arranged to minimise the size of the sample taking device . Further the components are manufactured of suitable materials having a low- weight. Furthermore, the components of the sample taking device is conveniently arranged in such a way that disposables, e.g. a solution source or a gas source, easily can be inserted, removed or replaced, and such that necessary tubings easily can be connected to for example the solution or gas source. Disposables Some of the components described above, for example the specimen collector, the tubings, the solution source or the gas source, are conveniently realised as disposable articles made in suitable materials. The specimen collector 120, 320 and the solution supplier 160, 320 can be realised as one or several catheters, tubes or tubings and the proximal end thereof can for example be introduced into the test site by means of a non-invasive technique using e.g. an introducer or by surgical cut-down. The part or parts of the specimen collector 120, 320 and the solution supplier 160, 320 introduced into the test object are manufactured of a biocompatible material or another suitable material that do not or minimally affect the test object or the taken samples adversely, e.g. a material having a low or non-adhesive, low or non-reactive and low or non-contaminating characteristics. In the case of taking blood samples, the lumen of the specimen collector is preferably treated or coated with a substance comprising an anticoagulant minimising the risk of blood clotting in the sample collector. The solution source can for example comprise a sodium chloride solution, a Ringer's solution or a test solution. The present invention has been described by means of exemplifying embodiments but it should be understood that the invention can be realised in other ways within the scope of the claims.

Claims

Claims
1. A specimen taking system (10) for automatic collection of specimen from a subject of an experiment (1, 301), comprising: - a portable specimen taking device (100, 300) configured to be removably attached to said subject (1, 301), said portable specimen taking device (100, 300) comprises a specimen collector (120, 320) and a test tube (140, 340), said specimen collector (120, 320) being configured to be connectable to a test site (130, 310) of said subject (1, 301) and to transport a taken specimen from said test site (130, 310) to said test tube (140, 340); storing means configured to store information relating to the specimen taking procedure; and processing means configured control said specimen taking procedure of said portable device (100, 300) in dependence of said stored information.
2. The system as recited in claim 1, wherein said sample taking device (100, 300) is configured to be removably attached to said subject (1, 301) by means of a necklace (101) having a Velcro fastening or snap locking.
3. The system as recited in claim 1 or 2, wherein a computerised unit (102,104) is communicatively connected to said specimen taking device (100) by means of a communication link (106), and configured to control said specimen taking procedure of said portable device and to store said information relating to said specimen taking procedure.
4. The system as recited in claim 1 or 2, wherein said sample taking device (100, 300) comprises means for receiving and storing information relating to said specimen taking procedure and means for controlling said sample taking procedure according to said information.
5. The system as recited in any of claim 1 - 4, further comprising a fraction assembler (740) configured to comprise said test tube (140, 340), a delivery means (750) configured to be connectable to a distal end of said specimen collector (120, 320) and to deliver a taken specimen to said test tube (140, 340); and a delivery control means (720) configured to be connectable to said delivery means (750) and to control the movement of said delivery means (750) and said fraction assembler (740).
6. The system as recited in any of claim 1 - 5, further comprising means configured to control the rate of movement of said taken specimen in said sample collector (120, 320) from said test site (130, 310) to said test tube (140, 340).
7. The system as recited in any of claim 1 - 6, wherein said portable specimen taking device comprises: — a solution source (150,350) configured to comprise a solution (152,352); - a solution supplier (160, 320) comprising a distal end connectable to said solution source (150, 350) and a proximal end connectable to said test site (130, 310) and devised to supply a volume of said solution (152, 352) to said test site (130, 310); and - a supply control unit (166, 170, 366, 330) arranged to control the supply of said solution (152, 352) to said test site (130, 310).
8. A portable specimen taking device (100, 300) for automatic collection of specimen from a subject of an experiment (1, 301), configured to be removably attached to said subject (1, 301), said specimen taking device (100, 300) comprises a specimen collector (120, 320) and a test tube (140, 340), said specimen taking device (100, 300) being configured to be connectable to atest site (130, 310) of said subject (1, 301) and to transport a taken specimen from said test site (130, 310) to said test tube (140, 340).
9. The device as recited in claim 8, further being configured to be removably attached to said subj ect ( 1 , 301 ) by means of a necklace (101) having a Velcro fastening or snap locking.
10. The device as recited in claim 8 or 9, further comprising means for receiving and storing information relating to said specimen taking procedure and means for controlling said specimen taking procedure in dependence of said information.
11. The device as recited in any of claim 8 - 10, further comprising means configured to control the rate of movement of said taken specimen in said specimen collector (120, 320) from said test site (130, 310) to said test tube (140, 340).
12. The device as recited in any of claim 8 - 11, further comprising: - a solution source (150, 350) configured to comprise a solution (152, 352); - a solution supplier (160, 320) comprising a distal end connectable to said solution 5 source (150, 350) and a proximal end connectable to said test site (130, 310) and devised to supply a volume of said solution (152, 352) to said test site (130, 310); and - a supply control unit (166, 170, 366, 330) arranged to control the supply of said solution (152, 352) to said test site (130, 310).
10 13. The device as recited in any of claim 8 - 12, further comprising a fraction assembler (740) configured to comprise said test tube (140, 340), a delivery means (750) configured to be connectable to a distal end of said specimen collector (120, 320) and to deliver a taken specimen to said test tube (140, 340); and a delivery control means (720) configured to be connectable to said delivery means (750) and to control the
15 movement of said delivery means (750) and said fraction assembler (740).
14. The device as recited in claim 13, wherein said delivery control means (720) is configured to control a longitudinal movement of said delivery means (750),
20 15. The device as recited in any of the claims 8 - 14, further comprising a support plate (710) having a first side (711) and an opposite second side (712), said support plate (710) comprising: - a first toothed wheel (715) connected to a first rod (716), which first rod (716) is configured to be longitudinal movable through a first hole of said support plate (710);
25 - a second toothed wheel (717) connected to said delivery control means (720) and configured to engage said first toothed wheel (715) when rotated by means of said delivery control means (720); - a second rod (719) configured to be longitudinal movable through a second hole of said support plate (710); and
30 - a first fixing plate (721) fixedly arranged at first ends of said first rod (716) and said second rod (719), said first fixing plate (721) comprising said delivery means (750).
16. A method for collecting specimen from a subject of an experiment according to the description.
17. A computer program product for collecting a specimen from a subject of an experiment, comprising means for performing the functions and steps according to any of the preceding claims.
18. A set of disposables for collecting specimen from a subject of an experiment, which set of disposables being configured to be used in any of the preceding claims.
19. A fraction assembler for collecting specimen from a subject of an experiment, said fraction assembler being configured to be used in any of the preceding claims.
PCT/SE2005/000243 2004-02-27 2005-02-23 Collection of a specimen WO2005082251A1 (en)

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US8116985B1 (en) 2006-03-17 2012-02-14 Battelle Memorial Institute Real time sampling, monitoring and exposure control of test animals
CN107396848A (en) * 2017-07-28 2017-11-28 广州大正新材料科技有限公司 A kind of method that bloodletting is carried out to pig

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US4696309A (en) * 1983-04-12 1987-09-29 Eberhart Stephan Portable apparatus for taking blood samples
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US8116985B1 (en) 2006-03-17 2012-02-14 Battelle Memorial Institute Real time sampling, monitoring and exposure control of test animals
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CN107396848A (en) * 2017-07-28 2017-11-28 广州大正新材料科技有限公司 A kind of method that bloodletting is carried out to pig
CN107396848B (en) * 2017-07-28 2021-06-25 广州大正新材料科技有限公司 Method for sampling blood of pig

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