This application is a 35 U.S.C. 371 National Phase of PCT Application Serial No. PCT/EP2014/065412 filed Jul. 17, 2014, which claims priority to French Application Serial No. 1357026, the disclosure of these prior applications are hereby incorporated by their entirety by reference.
The present invention relates to a device for sampling and dispensing a biological sample for biological analysis apparatuses.
The field of the invention is more particularly, but not exclusively, that of biological analysis systems, especially that of blood analysis systems.
Blood samples for biological analysis operations are traditionally collected by puncturing a vein.
Venous sampling requires a specific protocol performed by a qualified sample collector or nurse. This technique requires the sampling of a considerable quantity of blood (about 4 ml) from the patient. The blood sample is collected in a conventional tube.
To carry out the analyses, the tube is then introduced into a blood analyzer. A sampling needle is introduced into the tube in order to transfer a certain volume of the collected blood to a sampling system situated inside the analyzer.
The sampling system is in general formed by a sampling valve or by a syringe. It must permit the isolation or precise sampling of a blood aliquot of a predefined volume, which is used for the analysis.
Generally, the volume of blood actually used for the analysis is of the order of a few microliters. It is thus very small by comparison with the several milliliters taken from the patient.
Under certain conditions, venous sampling may prove difficult or even unfeasible. This may in particular be the case with children, or with certain individuals suffering from particular medical conditions (the obese, the elderly, victims of third-degree burns, etc.). In addition, for cultural reasons, it is sometimes necessary to minimize the volumes that are collected.
To address this type of problem, micro-sampling techniques have been developed.
Techniques for collecting samples of blood from capillary vessels are known in particular, which permit a reduction in the quantity of blood collected and make the sampling procedure easier. The blood from the capillary vessels is taken from a small puncture or a small superficial incision made, for example, on a finger tip, or on the sole of the foot in the case of neonates, or else on the earlobe.
The quantity of blood collected may be greatly reduced with this type of technique, but several approaches co-exist.
In some cases, the volume of blood collected may be sufficient, for example of the order of 200 μl, to be able to be harvested in a tube of the kind used for traditional venous sampling or in a mini-tube. The sample may therefore be transferred directly to the sampling system of the blood analyzer (such as the Micros Care ST® from Horiba Medical), via the sampling needle, in order to isolate the volume used for the analyses. In this case, the analyzer functions exactly as in the case of a venous sample collected in a tube.
In other cases, the volume of blood taken from the patient is very small, being the size of a droplet, that is to say of the order of 20 μl to 50 μl. In this case, the volume of the capillary blood sample is too small to be harvested and directly collected by the sampling system of the analyzer in a traditional tube. The volume of blood is then collected with the aid of a capillary or micro-capillary tube: the end of the capillary or micro-capillary tube is placed in contact with the blood droplet, and the blood fills the tube by capillary action.
In general, however, the volume of blood collected is still greater than the volume actually used for the analyses, and this necessitates further sampling of this volume prior to the analysis.
The patent document FR 2 774 765 in particular discloses a system for treating a blood sample that has been collected in a micro-capillary tube. The capillary tube containing the collected sample is introduced into a fluid conduit of the analyzer via an adapter. The blood sample thus finds itself connected to a hydraulic circuit, which is able to direct the sample toward a first pre-dilution container. Once the pre-dilution has been effected, the mixture is directed to the sampling system in order to determine exactly the volume that is necessary for the analysis.
The pre-dilution is made indispensable by the fact that the sampling valve used to extract the volume needed for the analysis requires a volume of liquid much greater than the volume of the micro-sampling.
The system is therefore complex, it uses up more blood than is necessary for the analysis, and, in addition, it involves hazardous manipulations of the capillary tube between the sampling of the blood and its insertion into an adapter.
The document JP 4807587 is also known, which discloses a system by which the volume of blood collected with a micro-capillary can be transferred directly to a sampling system, which permits isolation of the volume needed for the analysis. The micro-capillary tube used to collect the blood sample is inserted into an adapter. This adapter is placed in contact manually with the sampling needle of the analyzer. The volume needed for the analyses is then aspirated by the needle.
However, the sampling of the blood in the capillary tube is dependent on the correct positioning (without air admission) in which the operator holds the micro-capillary with respect to the needle. Indeed, if the contact between the capillary, via its adapter, and the needle is not leaktight, the sampling system will aspirate air and not the blood contained in the capillary.
In addition, the risks of contamination are not inconsiderable.
It is an object of the present invention to make available a device for sampling and dispensing biological samples by which it is possible to minimize the collected sample volumes and to better utilize these collected volumes.
Another object of the present invention is to make available a device for sampling and dispensing biological samples by which it is possible to minimize the manipulations of the sample and of the dilutions.
Another object of the present invention is to make available a device for sampling and dispensing biological samples by which it is possible to reliably collect precise volumes of samples.
Another object of the present invention is to make available a device for sampling and dispensing biological samples by which it is possible to simplify the manipulations that an operator has to perform between the collection of the sample from a patient and its transfer to an analysis system.
This aim is achieved with a sampler device for collecting a sample of biological fluid, characterized in that it comprises:
According to some embodiments, the capillary component and the base can be rigidly connected or made in one piece.
According to some embodiments, the sampler device can comprise a capillary tube and a base which is provided with a receiving means capable of receiving an end of said capillary tube and of keeping same leaktight.
In this case, the capillary component, which is a capillary tube, and the base can be separate elements that are joined together.
The sampler device can additionally comprise a fluid connection which connects the capillary component or the receiving means of a capillary tube and the first connector, in such a way as to allow a fluid connection to be established between the component or the capillary tube and the dispensing device.
This means of fluid connection can in particular comprise:
According to some embodiments, the sampler device can comprise:
The invention also relates to a device for dispensing biological fluid, which device comprises:
The transfer fluid can comprise, for example, a dilution fluid or a reagent.
The second connector can additionally comprise pressure means and/or spring means which are able to exert a pressure on the first connector when it is inserted into the second connector, so as to ensure the leaktightness of the connection.
The means for transferring transfer fluid can in particular comprise a fluid conduit and/or a tube.
According to some embodiments, the dispensing device can additionally comprise injection means capable of pushing a predefined volume of transfer fluid through the means for transferring transfer fluid in the direction of the second connector.
The injection means can comprise a syringe.
According to some embodiments, the dispensing device can additionally comprise a measuring container arranged in such a way as to be able to directly receive fluid issuing from a capillary component of a sampler device attached to the second connector.
According to some embodiments, the dispensing device can additionally comprise displacement means capable of positioning the second connector:
The displacement means can comprise:
According to another embodiment of the invention, a miniaturized dispensing device is proposed that can comprise a measuring container and a first receptacle.
Advantageously, the portable dispensing device according to this alternative embodiment can comprise injection means that are capable of pushing the liquid contained in said first receptacle exclusively through the fluid conduit and the capillary component. In this way, the risk of contamination of the blood sample is minimal.
Advantageously, the measuring container according to this alternative embodiment can further comprise means of optical and/or electrical analysis of the liquid that it contains.
According to another alternative of this embodiment, the miniaturized dispensing device can additionally have an interfacing means capable of connecting the miniaturized dispensing device at least mechanically to another analysis device.
Advantageously, the interfacing means according to this alternative embodiment can additionally comprise a fluid connection.
According to another aspect, a device for sampling and dispensing a biological fluid is proposed which comprises a dispensing device according to the invention and at least one sampler device according to the invention.
According to another aspect, an apparatus for analysis of biological fluids is proposed which comprises a dispensing device for biological fluid according to the invention.
The apparatus for analysis of biological fluids can additionally comprise at least one sampler device according to the invention.
Generally, the biological fluids or liquids for which the invention can be used can include bodily fluids such as blood, serum, plasma, saliva, urine, cerebrospinal fluid, or tissue extracts such as bone marrow.
According to some embodiments, the apparatus according to the invention can be intended to analyze a biological fluid that comprises blood.
According to some embodiments, the apparatus according to the invention can additionally comprise a sampling needle and branching means capable of transferring transfer fluid either to said sampling needle or to the dispensing device.
The sampling needle allows a sample of a biological fluid to be collected in a conventional open or closed tube. Thus, the apparatus can be suitable for measuring samples located either in conventional tubes or in capillary tubes.
According to another aspect, a method for sampling and dispensing a biological fluid is proposed, said method using a sampler device, provided with a capillary component, and a dispensing device, said method comprising a step of transfer and dilution of a sample of biological fluid contained in said capillary component by injecting a predefined volume of transfer fluid through the means for transferring transfer fluid and through said capillary component.
According to some embodiments, the sampling and dispensing method according to the invention can comprise:
According to some embodiments, the sampling and dispensing method according to the invention can be implemented with a biological fluid that comprises blood.
It can comprise a step of transferring a defined volume of transfer fluid suitable for obtaining a dilution directly adapted to at least one of the following biological analysis operations:
Other advantages and particular features of the invention will become clear on reading the detailed description of uses and of embodiments, which are in no way limiting, and of the following appended drawings:
Embodiments of devices according to the invention will now be described which are intended to be used in blood analysis apparatuses.
As has been explained above, the invention mainly comprises a sampler device and a dispensing device that is capable of receiving the sampler device.
With reference to
According to a first embodiment shown in
The capillary tube 13 is preferably made of a transparent material through which it is possible to verify the presence of blood on the inside. It can be made of glass or plastic, for example. The inner walls of the capillary tube can be treated specifically in accordance with the sampled biological fluid. For example, an anticoagulant can be deposited in the case of collecting a blood sample.
The sampler device 11 likewise comprises a base 14. This base 14 comprises a receiving means 12 or a receptacle 12 intended to receive the end of the capillary tube 13, in such a way as to hold the latter in place and ensure the leaktightness of the connection.
The base 14 likewise comprises a first connector 16 intended to attach the sampler device 11, reversibly and in a leaktight manner, to a second connector 22 of a dispensing device 21, as will be explained in detail below.
The base 14 also comprises a fluid connection 15 in the form of a continuous opening which opens into the first connector 16 and which is situated in the continuation of the receptacle 12 and of the capillary tube 13.
The base 14 can be made, for example, of a molded and/or machined plastic or polymer. It can be provided with raised areas or wings, as illustrated in
According to a second embodiment, shown in
The capillary component 13 comprises an internal conduit which is dimensioned in such a way that a biological fluid (for example blood) can be introduced into it by capillary action so as to fill it.
The base 14 likewise comprises a first connector 16 intended to attach the sampler device 11, reversibly and in a leaktight manner, to a second connector 22 of a dispensing device 21.
The base 14 also comprises a fluid connection 15 in the form of a continuous opening which opens into the first connector 16 and which is situated in the continuation of the internal conduit of the capillary component 13.
The capillary component 13 and the base 14 can be made, for example, from one piece of molded and/or machined plastic or polymer.
This piece can be provided with raised areas or wings in the area of the base 14, as illustrated in
The capillary component 13 can be of any external shape. In the embodiment shown in
In the two embodiments shown, the sampler device 11 with its capillary tube 13 constitutes a micro-sampling device for biological fluid and one which can be used directly for a capillary puncture, for example. Indeed, when the end of the capillary tube 13 is placed in contact with a drop of biological fluid (blood for example), the biological fluid rises by capillary action through the tube 13 until it fills the latter.
According to an advantageous aspect of the invention, the capillary tube 13 is dimensioned such that its internal volume defines a precise volume of sample, for example 10 microliters.
With reference to
This dispensing device 21 corresponds to the input interface of a blood analyzer. Its function is to receive sampler devices 11 (produced, for example, according to one or other of the two embodiments shown) with blood samples and to transfer these samples into analysis means of the blood analyzer.
It comprises a second connector 22 intended to receive the first connector 16 of the sampler device 11, as has been explained above.
The first connector 16 comprises lugs that are provided to engage in seats of the second connector 22, in such a way that, by rotation through a quarter of a turn, the sampler device 11 can be attached to the dispensing device 21, as illustrated in
The dispensing device 21 likewise comprises a fluid conduit 23 which opens into the second connector 22, in such a way as to establish a fluid connection with the capillary tube 13 through the base 14 when a sampler device 11 is connected. Advantageously, the capillary tube 13 does not touch the fluid conduit 23 when the base 14 is attached to the connector 22, by virtue of the presence of an air space in the fluid connection 15.
Referring to
According to an advantageous aspect of the invention, this measuring vessel 41 is intended to directly receive the blood sample collected in the capillary tube 13 and a volume of dilution liquid by which it is possible to obtain, in this vessel 41, the dilution or the mixture necessary for the measuring operations: for example a dilution of 1/300 for counting white blood cells or a dilution of 1/15000 for counting red blood cells.
To carry out these measurements, the measuring vessel 41 is connected, for example, to a device for optical or resistance measurements or for flow cytometry measurement, according to techniques well known to those skilled in the art.
To transfer the blood sample and the dilution liquid into the measuring vessel 41, the capillary tube is positioned opposite this measuring vessel 41 according to the configuration in
Dilution liquid is injected into the conduit 23 of the dispensing device 21, in the direction of the capillary tube 13. This dilution liquid firstly expels the blood sample from the capillary tube 13 into the measuring vessel 41, and it then flows through the capillary tube 13 into this measuring vessel 41.
A dosing system, for example a syringe, is used to inject a predefined quantity of dilution liquid into the conduit 23 and thus into the measuring vessel 41, in such a way as to achieve a precise rate of dilution in this measuring vessel 41 (the volume of blood sample contained in the capillary tube 13 being known).
The homogeneity of the solution in the measuring vessel 41 is ensured by an agitation system, for example by circulation of gas bubbles (bubbling).
Thus, according to advantageous aspects of the invention:
It will also be noted that sampler devices 11 can be supplied in the form of disposable sampling devices which are brought to the blood analyzer after sampling in order to perform the measurements.
To make the manipulations easier, the dispensing device comprises displacement means 40 in the form of a rotary system 40 as illustrated in
The dispensing device 21 can thus move between two positions:
Insofar as the rotation movement takes place in a plane perpendicular to the façade of the blood analyzer, the charging position corresponds to a position external to the apparatus, whereas the dispensing position corresponds to a position internal to the apparatus.
Referring to
A portable dispensing device is understood as a device that is capable of being easily manipulated and transported by an operator. For example, the external dimensions can be slightly greater than those of the sampler device in order to be able to contain the latter entirely. By way of example, dimensions of the order of 5×8×1 cm may be considered for a weight of the order of about one hundred grams. Advantageously, the dimensions of the portable dispensing device are such that it can be easily held in one hand. These sizes are given as examples in order to illustrate the portability of this embodiment of the invention and, as such, they do not constitute a limitation of the claimed scope of the invention.
The portable dispensing device 21 comprises in particular:
According to this alternative embodiment, the portable dispensing device 21 additionally has a seat 62 in the body 64. The seat 62 is capable of receiving at least part of the sampler device 11. When the displacement means 40 are actuated, manually or automatically, the sampler device is moved into said seat 62. In the case illustrated in
When the portable dispensing device 21 is in the dispensing position illustrated in
Moreover, in this dispensing position, the sampler device 11 is at least partially housed in the body 64 of the miniaturized dispensing device 21, in order to protect it, for example, from the external environment and from possible damage during the analyses.
The miniaturized dispensing device 21 additionally has an interfacing means 63 by which the miniaturized dispensing device 21 can be connected at least mechanically to another analysis device. According to another embodiment, this connection can be electronic and/or can include a fluid connection.
The first receptacle 42 may, for example, contain a diluent or a transfer liquid; it can include injection means for causing a fluid to circulate through the fluid conduit 23.
The second receptacle 41 consists of a measuring container into which are poured the mixture formed by the liquid contained in the first receptacle 42 and the blood sample contained in the capillary 13 of the sampler device 21. The second receptacle can include means for measuring and/or analyzing the mixture thus formed.
Of course, the invention is not limited to the examples that have been described, and many modifications can be made to these examples without departing from the scope of the invention.
Number | Date | Country | Kind |
---|---|---|---|
13 57026 | Jul 2013 | FR | national |
Filing Document | Filing Date | Country | Kind |
---|---|---|---|
PCT/EP2014/065412 | 7/17/2014 | WO | 00 |
Publishing Document | Publishing Date | Country | Kind |
---|---|---|---|
WO2015/007853 | 1/22/2015 | WO | A |
Number | Name | Date | Kind |
---|---|---|---|
4133304 | Bailey | Jan 1979 | A |
5638828 | Lauks et al. | Jun 1997 | A |
6284548 | Berndtsson | Sep 2001 | B1 |
20130142709 | Lin | Jun 2013 | A1 |
20160245793 | Samsoondar | Aug 2016 | A1 |
Number | Date | Country |
---|---|---|
2774765 | Aug 1999 | FR |
2003-159235 | Jun 2003 | JP |
WO 03044488 | May 2003 | WO |
WO 0175416 | Oct 2011 | WO |
Entry |
---|
International Search Report issued in International Patent Application No. PCT/EP2014/065412 dated Aug. 26, 2014. |
Number | Date | Country | |
---|---|---|---|
20160151776 A1 | Jun 2016 | US |