DK180759B1

DK180759B1 - Micro-dialysis probe with reinforcing tube

Info

Publication number: DK180759B1
Application number: DKPA202000195A
Authority: DK
Inventors: Jørgen Pedersen Hans; Allan Hansen Jesper
Original assignee: Flowsion As
Priority date: 2020-02-18
Filing date: 2020-02-18
Publication date: 2022-02-24
Also published as: EP4106629A1; CN115103628A; DK202000195A1; WO2021165235A1

Abstract

The present invention relates to a micro-dialysis probe for collecting substances of interest, e.g. ions or molecules, in particular from human or animal fluids or tissue. The micro-dialysis probe is of a kind having one or more flow channels carrying a perfusion fluid, the flow channel(s) being in contact with the tissue via one or more semi-permeable membranes. The substances of interest pass through the membrane(s) and are carried away by the perfusion liquid for further analysis. The micro-dialysis probe is formed as a probe system comprising a tube with at least one first conduit and one second conduit and a probe section, wherein a reinforcing tube with a third conduit is positioned within said second conduit.

Description

DK 180759 B1 1 MICRO-DIALYSIS PROBE WITH REINFORCING TUBE

BACKGROUND The present invention relates to a micro-dialysis probe for collecting substances of interest, e.g. ions or molecules, in particular from human or animal fluids or tissue. The micro-dialysis probe is of a kind having one or more flow channels carrying a perfusion fluid, the flow channel(s) being in contact with the tissue via one or more semi-permeable membranes. The substances of interest pass through the membrane(s) and are carried away by the perfusion liquid for further analysis. One prior document, US2007106206, disclose a blood treatment catheter pre- assembled with a stiffening tube is provided. The catheter includes a withdrawal lumen and a supply lumen each having distal split tube unjoined segments and an intermediate joined segment. The split tube segment of the supply lumen is provided with a sidewall aperture. The stiffening tube extends through the withdrawal split tip tube, out the distal end of the withdrawal tube, through the aperture of the supply split tip tube and through the split tip supply tube distal of the aperture, out the distal end of the split tip supply tube. When the stiffening tube is positioned inside the catheter, the aperture is adjacent to the withdrawal tube distal opening so as to minimize stiffening tube exposure and to provide a smooth exterior profile. In a preferred design, the tubes and their lumens, over their common length, are semi-circular to provide a circular profile for the catheter. The present invention further relates to a method of making a micro-dialysis probe in an easy and cost-effective manner.

There is a need to provide a micro-dialysis probe which is easy and cost effective to manufacture, and which is suitable for mass production. Furthermore, there is a need for a micro-dialysis probe which can collect a

DK 180759 B1 2 concentration of substances of interest which is representative of a local concentration at the position of the probe. Further it would be advantage for the micro-dialysis probe to have sufficiently small diameter to fit into the smallest existing venous catheters, e.g. umbilical catheters for new-borns, and which occupies as small a possible part of the cross section of the venous catheter.

SUMMARY OF THE INVENTION The objects are solved according to the features as given in the claim section. This includes the introduction of a probe system comprising a tube with at least one first conduit and one second conduit and a probe section, wherein a reinforcing tube with a third conduit is positioned within said second conduit.

The reinforcing tube may be substantially more rigid than said tube.

The probe system may be adapted for a perfusion fluid to be supplied to a sampling area within the probe section at a supply flow rate via the first conduit and returned from said sampling area at a second flow rate via the third conduit, — where the second flow rate is higher than the first flow rate.

The third conduit may have a smaller cross-sectional flow area than said first conduit and said second conduit.

In an embodiment a proximal end relative to the probe section of said reinforcing tube is connected within said second conduit at a proximal position relative to the probe section, thus enabling said probe system to be inserted by pushing the reinforcing tube.

— The proximal end of the reinforcing tube may be fixed to the inner of the second conduit in a sealing manner preventing fluid downstream relative to fixation from entering the area between the outside of the reinforcing tube and the second conduit.

DK 180759 B1 3 In an embodiment a distal end relative to the probe section of said reinforcing tube reaches out of an opening in the external wall of said tube at a position outside the body.

In an embodiment the perfusion fluid is directed for analysis via the third conduit. The membrane in an embodiment is positioned eccentrically onto the multi-tube covering one or more of the openings formed in the external tube wall in the dialysis probe section, where one such opening may be formed at the full circumference of the multi-tube.

FIGURES Fig. 1 lllustration of a section of double-lumen tube suitable for a dialysis probe system according to the present invention.

Fig. 2 Illustration of a dialysis probe system according to the present invention reaching trough a catheter. Fig. 3 lllustration of a dialysis probe section according to an embodiment of said invention including a semi-permeable membrane and reinforcing tube. Fig. 4 Illustration of a second section of the dialysis probe system according to an embodiment, where a reinforcing tube reaches out through an opening in the external tube wall.

DK 180759 B1 4

DETAILED DESCRIPTION OF THE INVENTION Fig. 1 illustrates a section of multi-tube (10) having two internal parallel conduits (15a, 15b), though any number of conduits is possible. The conduits (15a, 15b) could be arranged side-by-side, coaxially, or in any other possible and suitable configuration.

Fig. 2 illustrate an end part of a probe system (1) including the multi-tube (10) being equipped with a dialysis probe section (20) having a membrane (25) permeable to the substances to be samples. The membrane (25) may be a so- called ‘semi-permeable’ membrane where some substances can pass the wall of the membrane tube while other substances cannot. Preferably, the membrane (25) allow substances of interest, such as glucose, to pass, while sampling fluid flowing in the flow channels is prevented from passing.

In the present context the term ‘micro-dialysis probe’ should be interpreted to mean a probe which is adapted to collect substances of interest, in particular from human or animal tissue, such as blood, by means of dialysis, i.e. the substances of interest diffuse through a semi-permeable membrane to be collected by a perfusion fluid flowing in an interior part of the probe.

Further it enables the micro-dialysis probe to have sufficiently small diameter to fit into the smallest existing venous catheters, e.g. umbilical catheters for new- borns, and which occupies as small a possible part of the cross section of the venous catheter.

In one embodiment construction of the probe section (20) it is formed by (10) removing a wall section of the multi-tube (10) exposing one of the conduits (15a, 15b) and inserting a membrane (25) tube section into said conduit. A similar construction is to be seen in e.g. the publication E2257215.

DK 180759 B1 The present invention however is not limited to a construction as disclosed in figure 1 and 2, it may be formed e.g. by a membrane section (20) being extracted over the full circumference of the dialysis probe section (20), or part thereof. Further, rather than using a multi-tube (10) a plural of single tubes 5 could be clustered together etc., but will in general be referred to as tube (10) covering embodiments as illustrated with plural flow conduits (15a, 15b) within a single tube, or a collection of multiple single conduit tubes etc.

The probe (20) may be inserted into a catheter (50) e.g. central venous, or in — other tissues to be probed. The probe (20) and tube (10) need to be sufficiently soft and flexible to be introduced through the catheter (50) into position, and to ensure no damage is done to e.g. the tissue, and in general just to reduce any discomfort. When using such probe (20) and tube (10) systems in quite small sites, e.g. small blood vessels, in infants etc., they need to be of so small a diameter, that the insertion is not made difficult or impossible due to the softness and flexibility and dimensions of the probe.

Fig. 3 illustrates an embodiment end section of the probe system (1) with tube (10) and dialysis probe section (20) and showing a reinforcing tube (100) with a — third conduit (110) is positioned within the second conduit (15b).

In the illustrated embodiment a sampling fluid, or perfusion fluid, enters via the first conduit (15a) to the sampling area (30) formed in connection to the membrane (25) where it mixes with the substances diffusing from the tissue across the membrane (25) forming a sample fluid. The first conduit (15a) connects to the second conduit (15b) through the internal separating wall (14) to be directed to the outside of the body to be analysed, e.g. first collected in vials, directly connected to a microfluidic analysis chip for optical analysis etc.

— The said reinforcing tube (100) may be substantially more rigid than the tube (10), thus strengthening the tube (10) from within. The relatively soft and flexible tube (10) forming the outside contact to the tissues ensure e.g. that no damage is made, and eases the comfort, whereas the stiffer (relative to the tube (10))

DK 180759 B1 6 inner reinforcing tube (100) assists as one function in having the probe system (1) inserted. As illustrated in the embodiment of fig. 3, a proximal end of reinforcing tube (100) (proximal defined relative to the probe section (20)) is connected (55) within said second conduit (15b) at a proximal position relative to the probe section (20). The connection (55) is such that when pushing the reinforcing tube (100) forwards e.g. in a catheter (150) positioned intravenous (or into the tissue in general), then by the connection (55) the probe system (1) too is pushed forward, to have the probe section (20) positioned within the tissue etc.

In a further embodiment advantage of the reinforcing tube (100) can be used to define the return flow rate of the sample fluid. The return flow rate may be relevant to direct the sample fluid to the further analysis relatively quickly, both to ensure the measurements corresponds to the present situation as precise as possible, but also since undesired chemical reactions may occur that would influence the measurements.

To ease the manufacturing, and to keep cost down, the tube (10) formed e.g. as a multi-tube with plural internal conduits (15a, 15b), it is an advantage if one — single design could be made, which then subsequently could be calibrated, e.g. by the introduction of the reinforcing tube (100) selected according to the actual requirements.

When hollow reinforcing tube (100) having a third conduit (110) is inserted into the second conduit (15b) in a manner where the sample fluid from the sampling area (30) is forced to flow in the third conduit (110), the flow rate naturally will be higher that what would have been the situation if flowing in the third conduit (110).

Since the reinforcing tube (100) will fit into the second conduit (15b), the third conduit (110) naturally has a smaller cross sectional flow area than said second conduit (15b), and optionally also the first conduit (15a), possible having the same cross sectional flow area as the second conduit (15b).

DK 180759 B1 7 Therefore, if the sampling fluid, or perfusion fluid, is supplied to the sampling area (30) within the probe section (20) at a supply flow rate via the first conduit (15a), and returned from said sampling area (30) at a return flow rate via the — third conduit (110), where the second flow rate is higher than the supply flow rate.

At the proximal end part, the reinforcing tube (100) is fixed (55) to the inner of the second conduit (15b) in a sealing manner preventing fluid downstream relative to fixation (55) from entering the area between the outside of the reinforcing tube (100) and the second conduit (15b). This could be by glue or other fixing materials to connect the parts and having a sealing effect. In another embodiment the end-sealing and fixation elements (55) are biasing elements positioned at the circumference of the reinforcing tube (100) fixing it by friction.

The fixations (55) thus operate as sealing elements and at the same time ensures that by pushing, dragging or pulling the reinforcing tube (100), the rest of the probe system (1) naturally follows. The operator thus can insert the probe system (1) into a catheter (150) and insert it via the catheter (150) in position in the body tissue, blood vessels etc. by pushing the reinforcing tube (100).

As seen in fig. 4, in one embodiment a distal end of the reinforcing tube (100) (distal relative to the probe section (20)) reach out of an opening (16) in the external wall (12) of said tube (10) at a position outside the body, thus making it available to the operator.

This also enables the open distal end of the reinforcing tube (100) to be connected to e.g. an analysis device for further investigation and measurements.

In a not illustrated embodiment the membrane (25) (possible tube-shaped) is positioned eccentrically onto the multi-tube (10) rather than in a side wall as

DK 180759 B1 8 illustrated, where said membrane (25) covers one or more openings formed in the external tube wall (12) of the multi-tube (10) in the dialysis probe section (20). In one embodiment a single opening at the full circumference of the multi- tube (10). In this embodiment the rigidity, or stiffness, of the probe section (20)

is formed exclusive by the reinforcing tube (100), any internal separation wall (14) being fully removed in this section, whereas in another embodiment it supports internal separation wall (14) otherwise being the sole internal supporting structure.

Claims

DK 180759 B1 1 PATENTKRAV

Probe system (1) for collecting substances from liquids or tissues of humans or animals, which probe system (1) comprises - a single tube (10) with at least one first pipeline (15a) and one second pipeline (15b), and - a dialysis probe section (20) comprising a membrane (25) and which probe section (20) is adapted to be inserted into a catheter (50) and placed in the body tissue, blood vessels, etc. so that the flow tubes (15a, 15b) are in dialysis contact. with the tissue via the membranes (25), and where a perfusion liquid during use penetrates via the first pipeline (15a) at supply flow rate to a sampling area (30) generated in the probe section (20) in connection with the membrane (25) for collecting the substances of interest diffusing through the membrane, wherein a - reinforcing tube (100) with a third pipeline (110) is located in the second pipeline (15b), characterized in that the probe system (1) is arranged so that the perfusion fluid can be returned from sampling. the return area (30) at a return flow rate via the third pipeline (110), - where the return flow rate is higher than the supply flow rate.

Probe system (1) according to claim 1, wherein the reinforcing tube (100) is substantially more rigid than the tube (10).

Probe system (1) according to claim 1 or 2, wherein the third pipeline (110) has a smaller cross-sectional flow area than the first pipeline (15a) and the second pipeline (15b).

A probe system (1) according to any one of the preceding claims, wherein a proximal end of the reinforcing tube (100) relative to the probe section (20) is connected in the second pipeline (15b) in the proximal position relative to the probe section (20). ) thus enabling the probe system (1) to be inserted by pressing on the reinforcing tube (100).

DK 180759 B1 2

Probe system (1) according to claim 4, wherein the proximal end of the reinforcing tube (100) is fixed (55) to the interior of the second pipeline (15b) in a sealing manner that prevents liquid downstream of the fixation (55). ) penetrates into the area between the outside of the reinforcing pipe (100) and the second pipeline (15b).

A probe system (1) according to any one of the preceding claims, wherein a distal end of the reinforcing tube (100) relative to the probe section (20) during use reaches out of an opening (16) in an external wall (12) of the tube (10) in a position outside the body tissue.

Probe system (1) according to any one of the preceding claims, wherein during use the perfusion fluid is passed for analysis via the third pipeline (110).

A probe system (1) according to any one of the preceding claims, wherein the membrane (25) is located eccentrically on the tube (10) and covers one or more openings formed in an outer tube wall (12) in the dialysis probe section (20). .

Probe system (1) according to claim 8, wherein one such opening is subsequently formed in the full circumference of the tube (10).