WO2021165235A1

WO2021165235A1 - Micro-dialysis probe with reinforcing tube

Info

Publication number: WO2021165235A1
Application number: PCT/EP2021/053726
Authority: WO
Inventors: Jesper Allan Hansen; Hans Jørgen PEDERSEN
Original assignee: Flowsion A/S
Priority date: 2020-02-18
Filing date: 2021-02-16
Publication date: 2021-08-26
Also published as: DK180759B1; EP4106629A1; CN115103628A; DK202000195A1

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

MICRO-DIALYSIS PROBE WITH REINFORCING TUBE

BACKGROUND

The present invention relates to a micro-dialysis probe to be positioned intracorporeal 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 present invention further relates to a method of making such 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 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 for collecting substances from blood or tissue, said probe system comprising;

- a tube with at least one first conduit, and one second conduit, and

- a dialysis probe section comprising a membrane and a sampling area formed within the probe section in connection to the membrane, and which probe section is adapted to positioned intracorporeal with the membrane in dialysis connection to in the blood or tissue, and where the probe system is adapted for a perfusion fluid to be feed to the sampling area via first conduit at supply flow rate, wherein a reinforcing fiber is positioned within said second conduit, characterized in that said probe system is adapted for the perfusion fluid to be returned from said sampling area at a return flow rate via the second conduit, where the return flow rate is higher than the supply flow rate and is defined by the reinforcing fiber positioned within the second conduit. The reinforcing fiber may be a tube forming a third conduit, and where said probe system is adapted for the perfusion fluid to be returned from said sampling area at a return flow rate via the third conduit.

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

In an alternative embodiment, the reinforcing fiber is positioned in the second conduit such that the perfusion fluid flows at the outside of the reinforcing fiber, and where return flow rate is defined by an outer diameter of the reinforcing fiber relative to the inner diameter of the second conduit.

A proximal end of said reinforcing fiber or tube relative to the probe section is connected within said second conduit at the proximal position relative to the probe section, thus enabling said probe system to be inserted by pushing the reinforcing tube. By proximal is referred to the end of the probe system to be positioned intracorporeal, whereas distal is the end to be positioned extracorporeal. the proximal end of the reinforcing fiber or tube may be fixed to an 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.

The distal end of said reinforcing fiber or tube relative to the probe section may reach out of an opening in an external wall of said tube at a extracorporeal position, this being outside the body tissue or blood. The probe system may be adapted for said perfusion fluid is directed for analysis via the third conduit.

The membrane may be positioned eccentrically onto the tube covering one or more openings are formed in an external tube wall in the dialysis probe section. One such opening may be formed at the full circumference of the tube.

The reinforcing fiber or tube may be substantially more rigid than said tube. The reinforcing fiber or tube is adapted to remain within the second conduit when the probe system is in use.

FIGURES

Fig. 1 Illustration 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 Illustration 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.

Fig. 5 Illustration of a dialysis probe section according to an embodiment of said invention including a semi-permeable membrane and reinforcing fiber. DETAILED DESCRIPTION OF THE INVENTION

It should be understood, that the detailed description and specific examples, while indicating embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the detailed description.

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 illustrates 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. 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 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.

Exemplified as a multi-tube (10), a proximal end of the multi-tube (10) is defined as the end adapted to be positioned intracorporal, such as in the tissue or in a blood vessel of a human or animal. The distal end of the multi-tube is defined as the end adapted to be extracorporeal and is therefore accessible when the probe (20) formed at, or connected to, the proximal end of the multi-tube (10) is positioned intracorporal. In the same manner, respectively the proximal and distal ends of the probe system (1) is defined as the same end as the proximal and distal ends of the multi-tube (10). 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) to be positioned intracorporeal 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) positioned intracorporeal and 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 sampling area (30) is a volume within the probe (20), possible in direct connection to the membrane (25) which separates it from the tissue etc. The sampling area (30) may form part of the flow path of sampling fluid feed being feed to the sampling area (30), where it collects species diffusing across the membrane (25) from the tissue etc., and then being extracted to extracorporeal further analysis.

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 first (15a) and second (15b) conduits may be fluidically connected to the sampling area (30) forming part of the flow path for the sampling fluid.

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)) 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).

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.

The third conduit (110) may be fluidically connected to the sampling area (30) forming part of the flow path for the sampling fluid.

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 extracorporeal 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 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. Fig. 5 shows an alternative embodiment where a reinforcing fiber (100) is inserted and fixed in the second conduit (15b), such the perfusion fluid flows at the outside of the reinforcing fiber (100). In this embodiment the return flow rate is defined by an outer diameter of the reinforcing fiber (100) relative to the inner diameter of the second conduit (15b). This is different to the embodiment of fig. 4, where it is defined by the inner diameter of the third conduit (110).

The previous embodiments and features would also apply to the embodiment of fig. 5, except for the flow path of the return flow of perfusion fluid, the reinforcing and flow defining part (100) being a possible non-hollow fiber rather than a tube.

Claims

1. Probe system (1 ) for collecting substances from blood or tissue, said probe system (1) comprising; - a tube (10) with at least one first conduit (15a), and one second conduit (15b), and

- a dialysis probe section (20) comprising a membrane (25) and a sampling area (30) formed within the probe section (20) in connection to the membrane (25) and which probe section (20) is adapted to positioned intracorporeal with the membrane in dialysis connection to in the blood or tissue, and where the probe system (1) is adapted for a perfusion fluid to be feed to the sampling area (30) via first conduit (15a) at supply flow rate, wherein a reinforcing fiber (100) is positioned within said second conduit (15b), characterized in that said probe system (1) is adapted for the perfusion fluid to be returned from said sampling area (30) at a return flow rate via the second conduit (15b), where the return flow rate is higher than the supply flow rate and is defined by the reinforcing fiber (100) positioned within the second conduit (15b).

2. Probe system (1) according to claim 1 , wherein the reinforcing fiber (100) is a tube forming a third conduit (110), and where said probe system (1) is adapted for the perfusion fluid to be returned from said sampling area (30) at a return flow rate via the third conduit (110).

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

4. Probe system (1) according to claim 1 , wherein the reinforcing fiber (100) is positioned in the second conduit (15b) such that the perfusion fluid flows at the outside of the reinforcing fiber, and where return flow rate is defined by an outer diameter of the reinforcing fiber (100) relative to the inner diameter of the second conduit (15b).

5. Probe system (1) according to any of the previous claims, wherein a proximal end of said reinforcing fiber or tube (100) relative to the probe section (20) is connected within said second conduit (15b) at the proximal position relative to the probe section (20), thus enabling said probe system (1) to be inserted by pushing the reinforcing tube (100).

6. Probe system (1) according to claim 5, wherein said proximal end of the reinforcing fiber or tube (100) is fixed (55) to an 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).

7. Probe system (1 ) according to any of the previous claims, wherein a distal end of said reinforcing fiber or tube (100) relative to the probe section (20) reach out of an opening (16) in an external wall (12) of said tube (10) at a position outside the body tissue.

8. Probe system (1) according to any of the previous claims, wherein the probe system (1 ) is adapted for said perfusion fluid is directed for analysis via the third conduit (110).

9. Probe system (1) according to any of the previous claims, where the membrane (25) is positioned eccentrically onto the tube (10) covering one or more openings are formed in an external tube wall (12) in the dialysis probe section (20).

10. Probe system (1) according to claim 9, where one such openings then is formed at the full circumference of the tube (10).

11. Probe system (1) according to any of the previous claims, wherein said reinforcing fiber or tube (100) is substantially more rigid than said tube (10).