The invention relates to the field of the sampling of biological liquid in particular urine for applications such as the medical research on human health or the diagnostic of human diseases or nutritional deficiencies such as for infant or elderly people.
Despite the wide range of diagnostic methods and equipment, there is still an unmet need for convenient and hygienically safe tools enabling to collect biological liquids in particular urine from human body in a manner that enables to reliably perform analysis and/or diagnostics based on samples of the liquid.
A problem of sampling urine, in amount sufficient for biological analysis, lies in that it is not easy to collect such liquid on demand especially from infants or young children or functionally limited people such as disabled or elderly persons.
A solution described in WO2017168388 consists in proposing a solution of diaper for the selection of biological samples comprising an accumulator formed as an absorbing band removably and externally connected to the diaper, in particular positioned about a through-hole collecting area of the diaper.
In co-pending international patent application PCT/162017/056789, a method for the identification of compounds of human urine and/or determination of analytical parameters such as pH is described. The method utilizes a kit comprising the accumulator of WO2017168388 and urinary indicating bands comprising multiple indicators, including colour reagents, which are wetted by contact with the urine accumulator. The urinary indicating bands can be held on an analysis device which bears colorimetric scales to compare the change of colour of the indicators of the band with the colorimetric scale to analyse the compounds and analytical parameters.
However, other more sophisticated analysis such as microscopy, chromatography, or others, require the collection of samples of a minimal volume of liquid. Urine is composed of more than 15 analytes (glucose, ketones, albumin, leucocyte, erythrocytes, etc.) which are interesting for fine analysis. Todays' analysis provide a loss of information due to the techniques of sampling which are not reliable and safe enough.
Therefore, there is a need for a solution to collect enough biological liquid in particular urine with the convenience of the accumulator of WO2017168388 and also in a manner that enables the subsequent in-depth analysis of the liquid such as microscopy and the like to be successfully carried out.
In particular, there is a need for collecting and sampling biological liquid in sufficient amount, rapidly, safely and without risk of cross-contamination.
The invention aims at providing solutions to the above-identified problems.
In particular, the invention relates to a kit for the sampling of biological liquid in particular urine comprising:
a flexible accumulator of biological liquid adapted to collect the liquid from a human body formed as an elongated band comprising at least one liquid absorbing layer and at least one support layer attached to the liquid absorbing layer;
at least one closed recipient comprising a tubular container with a tubular sidewall portion and a bottom portion forming an elongated tubular cavity and a closing lid sealingly connected to the open end of the sidewall portion opposite the bottom portion;
wherein the accumulator is configured for being inserted in the tubular cavity of the container through the open end when the closing lid is removed;
wherein the recipient further comprises holding means configured for maintaining the accumulator in position in the recipient and distant from the bottom portion of the container upon re-closing of the container to enable liquid previously absorbed by the accumulator to be collected in the recipient in a reserved volume part of the cavity not occupied by the accumulator, between the bottom portion of the recipient and the accumulator, when the recipient is centrifuged in a centrifugal liquid collecting machine.
Preferably, at least the length of the absorbing layer of the accumulator is shorter than the internal depth of the tubular cavity. More preferably, the length of the accumulator is shorter than the internal depth of the tubular cavity. Such configuration ensures that at least the part of the accumulator which is charged with biological liquid can be entirely inserted in the recipient in non-folded manner in the axial direction of the recipient.
Therefore, the invention provides an easy and reliable solution to sample liquid such as urine while making sure a sufficient amount of liquid is separated from the accumulating element well reserved in a safe and uncontaminated volume before it can be analysed by microscopy or other tools. Generally, the recipient is capable to hold the accumulator while avoiding it to collapse in the reserved part even at elevated centrifugal speeds, e.g. in a range of 500-800 rpm.
The “length” of the accumulator or of the absorbing layer represents the maximal dimension in the longitudinal direction of the considered element that corresponds to the direction of insertion of the accumulator in the recipient.
In particular, the internal surfaces and internal volume of the closed recipient of the kit is preferably sterile before the first opening to receive the accumulator inside. The recipient can be made sterile by any suitable non-intrusive sterilisation means such as by heat and/or irradiation, e.g. gamma rays.
The closing lid may be any kind of seal member such as a multiple-use plastic lid and/or a single-use sealing membrane. Preferably, the lid is formed as a plastic cap and preferably has reversible connection means such as a thread and the open end of the container has a complementary connection means such as a thread.
Preferably, the holding means are configured to define a reserved part of the volume of the cavity not occupied by the accumulator when held in the recipient of between 1 and 10 ml and/or of between 0.5 and 2.5 cm long. Most preferably, the reserved part of the volume is between 1 and 10 ml more preferably between 1 and 3 ml and/or between 0.8 and 2.5 cm more preferably between 1 and 1.5 cm. The kit is thus well adapted to very small quantities of liquid to be collected and reserved.
Preferably, the length of the absorbing layer is shorter than the length of the volume part of the cavity situated above the holding means. As a result, the absorbing layer can be entirely contained in the recipient once closed thereby ensuring no spillage of liquid outside the recipient during centrifugation.
In a preferred mode the holding means comprises at one abutment member located in the reserved volume part of the cavity and sized to hold the accumulator above the bottom portion of the container. Preferably, the accumulator is held at a distance between 1 and 3 cm above the bottom portion of the container.
More specifically, the holding means comprises a series of ribs provided at the internal surface of the tubular sidewall portion. Most preferably, the ribs protrudes inwardly from the tubular internal surface and are distributed over the circumference of the tubular internal surface. Such ribs configuration provides the advantage to offer an efficient support for the accumulator by well distributing reaction force during the centrifugation operation and so prevents the accumulator from collapsing in the recipient.
Preferably, the ribs are oriented along the axial direction of the elongated tubular cavity and end by free edges in direction of the open end of the container. The neighboured ribs may be distanced one another from a linear distance of less than 2 cm, preferably less than 1.5 cm, most preferably between 1.2 and 0.5 cm, to hold the accumulator. In particular, the support layer at least when the accumulator is partially rolled in the recipient about the longitudinal axis.
In particular, the tubular portion of the container has a diameter comprised between 1 and 5 cm, more preferably between 1 and 3.5 cm, most preferably between 1.5 and 2.5 cm.
The accumulator is relatively flexible although resistant to traction forces and to tearing. The resistance to tearing of the accumulator is preferably obtained by the mechanical properties of the support layer. In particular, the support layer is made of a material having higher tear strength than the material of the absorbing layer.
The configuration of the ribs and/or diameter of the recipient enables to insert the accumulator in an at least partially rolled fashion about its longitudinal axis so that its rigidity is enhanced to prevent it from collapsing during centrifugation. Furthermore, this arrangement of properly distanced ribs reduces the risk of the flexible accumulator to collapse while providing enough reserved volume for liquid.
In another mode, the abutment member is a removable elongated insert of smaller length than the internal depth of the cavity, e.g. with a transversal cross-section having the general form or configuration of a cross, a full or partial tube or a transversal grid.
The insert is preferably in place in the closed recipient and is also sterile. The insert may be made of a rigid polymer material such as polypropylene or polyethylene. For example, the insert can be a small grid arranged for separating the volume of the cavity in two parts; an upper part of the cavity for receiving the accumulator and a lower part of the cavity for forming the reserve for the centrifuged liquid.
In another mode, the holding means comprise an elongated rigid support platform comprising a holding surface configured for receiving the accumulator and comprising attachment means configured for being attached to the internal side of the lid, the support platform having a length shorter than the internal depth of the tubular cavity to be fixed to the lid at distance from the bottom portion of the recipient when closed.
In particular, the support platform is a rectangular plate-like member larger than the width of the accumulator but smaller than the width or diameter of the tubular sidewall portion.
This platform configuration provides the advantage to avoid rolling the accumulator before inserting it inside the recipient. The support platform can be introduced in the container without being deformed while holding the accumulator, preferably flat. As a result, the potential loss of liquid is reduced, as the absorbing layer is kept flat and uncompressed. The risk of contamination is also limited.
Preferably, the support platform comprises at least one retaining member configured for holding the accumulator at least in the axial direction of the container, in particular with the support layer being retained in contact on the support platform.
Preferably, the retaining member may comprise any one or more of: a slider on the platform, an attachment pin, a mechanical adhesive or a chemical adhesive and combinations thereof. The slider(s) may advantageously be formed integrally with the platform in a single piece, such as made out of rigid plastic.
With such arrangement of the retaining means, the accumulator is fixed on the platform and is prevented from moving because of the centrifugation forces.
Preferably, the liquid absorbing layer can be a relatively thick compressible layer of fibres, e.g. 0.5 to 2 cm, preferably synthetic fibres such as made of viscose and polystyrol. The support layer or layers may be a traction resistant layer of medical paper or woven layer. The layer can be made of polymer and/or paper. In particular, the support layer can comprise a polymer-coated film of cellulose or paper. The support layer may have a thickness between 0.2 and 1 mm.
The accumulator may have a length between 5 and 10 cm and a width between 2 and 4 cm.
The accumulator may optionally comprise additional layers such as an attachment layer on top of the support layer and opposite to the liquid absorbing layer. The attachment layer may have a non-permanent adhesive inner surface configured for connecting the support and absorbing layers in a removable manner to the diaper.
The support layer and/or attachment layer may define the greatest length and width of the accumulator. The liquid absorbing layer may have a length and width, e.g. 10 to 50% shorter, than the length and width of the support layer. The support layer may have a length and width shorter, e.g. 10 to 70% shorter than the length and width of the attachment layer.
It should be noted that the attachment layer may also be part of the diaper. In such case, the accumulator only comprises the liquid absorbing layer and the support layer attached one another.
Furthermore, the kit may comprises a diaper comprising at its external side a collecting area through which the accumulator is removably fixed by means of an attachment layer of dimensions larger in all directions than the surface of the support layer of the accumulator to protect the accumulator in the collecting area during collection of the biological liquid, the attachment layer comprising a reversible, pressure sensitive adhesive inner surface arranged for holding in a removable manner the accumulator in the collecting area.
In particular, the collecting area may be e.g. a hole through the diaper or a liquid permeable wall area in the thickness of the diaper.
The invention further relates to a method for collecting biological liquid in particular urine from the kit as aforementioned, wherein after the absorbing layer of the accumulator is charged with liquid, the accumulator is inserted in the container while being held by the holding means and at distance from the bottom portion of the container, the recipient is closed by the closing lid and the recipient is centrifuged in a liquid centrifugal machine to collect liquid in the reserved volume part of the elongated cavity of the container, while the holding means hold the accumulator in place thereby keeping the reserved part of the cavity unoccupied by the accumulator when collecting liquid therein.
Preferably, the reserved part of the cavity is of about 1 to 5 ml.
Preferably, the recipient is closed by the closing lid, with the interior cavity being sterile before opening, preferably by removal of the closing lid and insertion of the accumulator in the container and subsequent closing, preferably by the closing lid, for sampling of the liquid by centrifugation. Preferably, the closing lid is threaded in a removable fashion to a threaded portion of the container to close its open end.
Features described in relation to one aspect may equally be applied to other aspects of the invention.
Embodiments of the invention will now be described, by way of preferred examples only, with reference to the accompanying drawings, in which:
A first mode of the sampling kit 1 of the invention is illustrated in
The recipient 3 comprises an elongated tubular container 4 and a closing lid 5. In the closed configuration before first use, the interior surfaces of the recipient are preferably sterile. The process of sterilization can occur during the manufacturing of the container such as by gamma irradiation or other suitable techniques. The closing lid 5 is connected to the container in removable and repeatable manner such as by a threading assembly. The connection is preferably a sealing connection in the sense that the interior environment can be maintained sterile during an extensive period of storage.
In a possible mode, the container can be closed in sterile fashion before its first opening by means of a closing lid formed by at least one peelable sealing membrane. A combination of a threaded lid associated to or on top of a peelable sealing membrane is also a possible closing lid.
As shown in
An example of liquid accumulator 2 is represented on
The support layer 11 is designed to avoid the absorbing layer to tear apart. It can be a tear resistant film made of polymer and/or cellulose or paper. Its dimensions (L, w) are preferably higher than the dimensions (L1, w1) of the absorbing layer 10. In particular, its length L can be of 5 to 12 cm and its width w can be of 1.5 to 4 cm.
According to an aspect of the invention, the tubular recipient 3 comprises holding means designed for holding the accumulator 2 when it is inserted in the container, such holding means being such that it avoids the accumulator from collapsing during centrifugation. In this mode, the holding means comprises a series of holding ribs 12, 12a, 12b, 12c, 12d oriented in the longitudinal direction I and protruding on the internal surface of the sidewall portion 6. The ribs comprise free edges 13; at least some of them being located at distance M from the bottom portion 7 such that a reserved volume part 14 of the cavity is provided between the bottom portion and an upper cavity portion 15 without ribs. The diameter d of the sidewall portion of the container and the distance M are thus defined to create a volume, which is commensurate with the amount of liquid contained in the accumulator and/or the amount of liquid required for subsequent analysis. The diameter d of the container is preferably smaller than the width w of the accumulator, preferably 1.5 to 3 times smaller, such that the accumulator needs to be rolled about its longitudinal axis to be properly inserted in the container open as illustrated in
The number of ribs can be variable, preferably between 2 and 10. They are preferably distributed over the circumference of the internal surface of the sidewall portion. They may end before the bottom portion or may extend down to the bottom portion. The neighbouring ribs may be distanced from a small distance such as 3 to 5 mm; whereas the difference between the internal diameter of the container d and the longest distance between ribs d1 (i.e. “d-d1”) is designed to provide sufficient support to the accumulator. For example, the radial thickness of each rib is between 0.8 and 2 mm. Preferably, the container and ribs are formed as a single integral piece of polymer such as by blow moulding, extrusion or injection.
Other shapes of the holding means are represented as possible examples in
For example, in
In
In
Once closed or re-closed by the threaded lid with the accumulator fitted in, the recipient can be centrifuged in a conventional medical centrifugal machine for separating the liquid from the accumulator. The centrifugal speed can be controlled between 200 and 800 rpm between e.g. 20 seconds and 5 minutes, to force liquid 25 to settle in the reserved part of the volume beside the bottom portion. The volume of sampled liquid may vary from 1 to 5 ml depending on the capacity of the accumulator and the capacity of the reserved part 14.
A second embodiment is illustrated in relation to
The support platform can be attached to the recipient, either to the container or lid, by any suitable means, provided the support platform is maintained at distance from the bottom portion 7 of the tubular container such as to provide the reserve part 14 of volume for liquid. For example, the support platform comprises a connection member 40, e.g. a pin, at its proximal end which engages a complementary connection member 41, e.g. a hose provided at the interior side of the lid 5. The pin and hose may be assembled e.g. by force fitting or screwing or any other suitable assembly means resisting centrifugation.
The kit 1 of the invention may encompass a collecting diaper 42 as illustrated in
The invention further relates to a method for sampling a biological liquid, in particular urine, by means of the kit as described generally or in any of the preceding preferred modes.
The method comprises the following steps: