CN115103628A

CN115103628A - Microdialysis probe with reinforced tube

Info

Publication number: CN115103628A
Application number: CN202180015023.8A
Authority: CN
Inventors: J·A·汉森; H·J·佩德森
Original assignee: Florion Corp
Current assignee: Florion Corp
Priority date: 2020-02-18
Filing date: 2021-02-16
Publication date: 2022-09-23
Also published as: WO2021165235A1; EP4106629A1; DK180759B1; DK202000195A1

Abstract

The present invention relates to a microdialysis probe for collecting substances of interest, such as ions or molecules, in particular from fluids or tissues of humans or animals. A microdialysis probe is a probe having one or more flow channels for the delivery of perfusion fluid, which flow channel or channels are in contact with tissue through one or more semi-permeable membranes. The substance of interest passes through one or more semi-permeable membranes and is carried away by the perfusate for further analysis. The microdialysis probe is formed as a probe system comprising a tube with at least one first and one second tube, and a probe section, wherein a reinforcement tube with a third tube is located within the second tube.

Description

Microdialysis probe with reinforced tube

Technical Field

The present invention relates to a microdialysis probe for positioning in a body for collecting substances of interest, such as ions or molecules, in particular from fluids or tissues of humans or animals. A microdialysis probe is a probe having one or more flow channels for the transport of perfusion fluid, which flow channel or channels are in contact with the tissue through one or more semi-permeable membranes. The substance of interest passes through one or more semi-permeable membranes and is carried away by the perfusate for further analysis.

The invention also relates to a method for manufacturing such a microdialysis probe in a simple and economical manner.

Background

It is desirable to provide a microdialysis probe that is easy and inexpensive to manufacture and that is suitable for mass production. Furthermore, there is a need for a microdialysis probe capable of collecting a concentration of a substance of interest that is representative of the local concentration at the probe location. Furthermore, it is advantageous that the microdialysis probe has a sufficiently small diameter to fit into the smallest existing venous catheters (e.g. umbilical catheters for neonates) and that the microdialysis probe occupies as small a portion of the venous catheter cross section as possible.

Disclosure of Invention

These objects are solved according to the features given in the claims section.

This includes introducing a probe system for collecting a substance from blood or tissue, the probe system comprising:

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

a dialysis probe section comprising a membrane and a sampling area formed within the probe section in connection with the membrane,

and the probe section is adapted to be positioned in the body in such a way that the membrane is dialytically connected in blood or tissue, and wherein the probe system is adapted to supply perfusion fluid to the sampling region via the first tubing at a supply flow rate, wherein the reinforcement fibres are positioned within the second tubing, characterized in that the probe system is adapted to return perfusion fluid from the sampling region via the second tubing at a return flow rate, wherein the return flow rate is higher than the supply flow rate and is defined by the reinforcement fibres positioned within the second tubing.

The reinforcing fibre may be a tube forming a third conduit, and wherein the probe system is adapted to return perfusion fluid from the sampling region via the third conduit at a return flow rate.

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

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

The proximal end of the reinforcing fiber or tube relative to the probe section is connected within the second conduit at a proximal location relative to the probe section, enabling the probe system to be inserted by pushing the reinforcing tube. "proximal" refers to the end of the probe system that is to be positioned inside the body, while "distal" refers to the end that is to be positioned outside the body.

The proximal end of the reinforcing fiber or tube may be secured to the interior of the second conduit in a sealing manner preventing fluid downstream relative to the securing member from entering the region between the exterior of the reinforcing tube and the second conduit.

The distal end of the reinforcing fiber or tube relative to the probe section may protrude from an opening in the outer wall of the tube at an extracorporeal location, which is external to the body tissue or blood.

The probe system may be adapted to guide said perfusion fluid via the third conduit for analysis.

The membrane may be positioned eccentrically on the tube, covering one or more openings formed in the outer tube wall of the dialysis probe segment. One such opening may be formed over the entire circumference of the tube.

The reinforcing fibres or tubes may be much more rigid than the tubes.

The reinforcing fiber or tube is adapted to be retained within the second conduit when the probe system is in use.

Drawings

Fig. 1 shows a portion of a dual lumen tube suitable for use in a dialysis probe system according to the present invention.

Figure 2 shows a dialysis probe system according to the present invention passing through a catheter.

Fig. 3 shows a dialysis probe segment comprising a semi-permeable membrane and a reinforcement tube according to an embodiment of the invention.

Fig. 4 shows a second part of the dialysis probe system according to an embodiment, wherein the reinforcement tube protrudes through an opening in the outer tube wall.

Fig. 5 shows a dialysis probe segment comprising a semi-permeable membrane and reinforcing fibers according to an embodiment of the invention.

Detailed Description

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 this detailed description.

Fig. 1 shows a portion of a manifold (10) having two conduits (15a, 15b) in parallel interior, although any number of conduits is possible. The conduits (15a, 15b) may be laid side by side, coaxially or in any other possible and suitable configuration.

Fig. 2 shows an end portion of the probe system (1) comprising a multi-tube (10) equipped with a dialysis probe section (20) having a membrane (25) permeable to the substance to be sampled. The membrane (25) may be a so-called "semi-permeable" membrane in which some substances are able to pass through the wall of the membrane tube, while other substances are not. Preferably, the membrane (25) allows passage of a substance of interest, such as glucose, while preventing passage of a sampling fluid flowing in the flow channel.

In the present context, the term "microdialysis probe" should be interpreted as a probe suitable for collecting a substance of interest, in particular from human or animal tissue (such as blood), by dialysis, i.e. the substance of interest diffuses through a semi-permeable membrane to be collected by perfusion fluid flowing inside the probe.

Furthermore, it enables the microdialysis probe to have a diameter small enough to fit into the smallest existing venous catheters (e.g. umbilical catheters for neonates) and to occupy as small a portion of the venous catheter cross section as possible.

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

However, the invention is not limited to the configuration disclosed in fig. 1 and 2, which may be formed by a membrane portion protruding over the entire circumference or a part of the circumference of the dialysis probe segment (20), for example. Furthermore, rather than using multiple tubes (10), multiple single tubes may be grouped together or the like, but will generally be referred to as a tube (10) to cover embodiments having multiple flow-through conduits (15a, 15b) within a single tube as shown, or a collection of multiple single conduits, or the like.

Taking the multi-tube (10) as an example, the proximal end of the multi-tube (10) is defined as the end adapted for positioning in vivo, e.g. in a tissue or a blood vessel of a human or animal. The distal end of the manifold is defined as the end adapted to be outside the body and is therefore accessible when a probe (20) formed on or connected to the proximal end of the manifold (10) is positioned inside the body. In the same way, the proximal and distal ends of the probe system (1) are defined as the same ends as the proximal and distal ends of the manifold (10), respectively.

The probe (20) may be inserted into a catheter (50), such as a central vein, or other tissue to be probed. The probe (20) and tube (10) need to be sufficiently soft and flexible to be introduced into position through the catheter (50) and ensure that no damage is caused to e.g. tissue, and generally only to reduce any discomfort. When such probe (20) and tube (10) systems are used in very small locations, such as small blood vessels of infants and the like, these probe and tube systems need to have a small diameter so that insertion is not difficult or impossible due to the softness, flexibility and size of the probe.

Fig. 3 shows an embodiment end part of the probe system (1) with a tube (10) to be positioned in the body and a dialysis probe section (20), and shows that a reinforcement tube (100) with a third tubing (110) is positioned within the second tubing (15 b).

In the shown embodiment, the sampling fluid or perfusion fluid enters via a first conduit (15a) a sampling region (30) located in the body and formed in connection with a membrane (25), where it mixes with a substance diffusing from the tissue through the membrane (25) to form the sample fluid. The sampling region (30) is the volume within the probe (20) that can be directly connected to a membrane (25) that separates it from tissue or the like. The sampling region (30) may form part of a flow path of a sample fluid feed supplied to the sampling region (30), where substances diffusing from tissue or the like across the membrane (25) are collected and then extracted for further analysis outside the body.

The first conduit (15a) is connected to the second conduit (15b) by an internal separation wall (14) to be guided outside the body to be analyzed, for example first collected in a vial, directly connected to a microfluidic analysis chip for optical analysis, or the like.

The first tubing (15a) and the second tubing (15b) may be fluidly connected to the sampling region (30), forming part of a flow path for the sampling fluid.

The reinforcing tube (100) may be much more rigid than the tube (10), thereby internally reinforcing the tube (10). The relatively soft and flexible tube (10) forming the contact with the outside of the tissue ensures, for example, that no injuries are caused and that it is comfortable and easy to use, while the inner stiffening tube (100), which is harder (relative to the tube (10)), facilitates the insertion of the probe system (1) as a functional element. As shown in the embodiment of fig. 3, the proximal end of the stiffening tube (100) (defined relative to the probe section (20)) is connected (55) within said second duct (15b) at a proximal position relative to the probe section (20). The connector (55) is such that when the enhancement tube (100) is pushed forward, for example in a catheter (150) positioned intravenously (or generally within tissue), then the probe system (1) is also pushed forward through the connector (55) to position the probe section (20) within the tissue or the like.

In another embodiment, the advantages of the intensifier tube (100) can be used to define the return flow rate of the sample fluid. The return flow rate may be relevant for directing the sample fluid to further analysis relatively quickly, both to ensure that the measurement corresponds as accurately as possible to the current situation, and because undesired chemical reactions may occur that may affect the measurement.

In order to simplify the manufacture and reduce costs, the tube (10) is formed, for example, as a multiple tube with a plurality of internal ducts (15a, 15b), it being advantageous if a single design can be made which can then be calibrated, for example by introducing a reinforcing tube (100) selected according to the actual requirements.

When the hollow reinforcement tube (100) with the third tubing (110) is inserted into the second tubing (15b) in such a way that the sample fluid from the sampling area (30) is forced to flow in the third tubing (110), the flow rate will naturally be higher than in the case of flow in the third tubing (110).

Since the reinforcement pipe (100) is to be fitted into the second duct (15b), the third duct (110) naturally has a smaller cross-sectional flow area than said second duct (15b), and optionally the first duct (15a) may also have the same cross-sectional flow area as the second duct (15 b).

Thus, if a sampling fluid or perfusion fluid is supplied to a sampling region (30) within a probe section (20) via a first conduit (15a) at a supply flow rate and returned from said sampling region (30) via a third conduit (110) at a return flow rate, wherein the second flow rate is higher than the supply flow rate.

The third conduit (110) may be fluidly connected to the sampling region (30), forming part of the flow path of the sampling fluid.

At the proximal end portion, the reinforcement tube (100) is fixed in a sealed manner to the inside of the second duct (15b) to prevent the fluid downstream with respect to the fixing member (55) from entering the region between the outside of the reinforcement tube (100) and the second duct (15 b). This may be by glue or other fixing material joining the parts and having a sealing effect. In another embodiment, the end seal and securement element (55) is a biasing element positioned on the circumference of the reinforcement tube (100) securing the reinforcement tube by friction.

The fixture (55) thus operates as a sealing element while ensuring that the rest of the probe system (1) naturally follows by pushing, dragging or pulling the reinforcement tube (100). Thus, the operator can insert the probe system (1) into the catheter (150) and insert the probe system into an appropriate position in the body tissue, blood vessel, etc. via the catheter (150) by pushing the reinforcing tube (100).

As shown in fig. 4, in one embodiment, the distal end of the stiffening tube (100) (relative to the distal end of the probe section (20)) protrudes from an opening (16) in the outer wall (12) of the tube (10) at an extracorporeal location outside the body, thereby making the distal end of the stiffening tube available to the operator.

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

In an embodiment not shown, the membrane (25) (possibly tubular) is positioned eccentrically on the multi-tube (10), rather than in the side wall as shown, wherein the membrane (25) covers one or more openings formed in the outer wall (12) of the tubes of the multi-tube (10) in the dialysis probe section (20). In one embodiment, there is a single opening over the entire circumference of the manifold (10). In this embodiment, the rigidity or stiffness of the probe section (20) is formed solely by the reinforcing tube (100) in which any internal dividing wall (14) is completely removed, while in another embodiment the reinforcing tube supports the internal dividing wall (14), which is otherwise the only internal support structure.

Fig. 5 shows an alternative embodiment in which the reinforcing fibers (100) are inserted and fixed in the second duct (15b) so that the perfusion fluid flows outside the reinforcing fibers (100). In this embodiment, the return flow rate is defined by the outer diameter of the reinforcing fibers (100) relative to the inner diameter of the second duct (15 b). This is different from the embodiment of fig. 4, where the return flow rate is defined by the inner diameter of the third conduit (110).

In addition to the flow path for the perfusion fluid to flow back, the foregoing embodiments and features also apply to the embodiment of fig. 5, and the reinforcing and flow-defining portion (100) may be a non-hollow fiber rather than a tube.

Claims

1. A probe system (1) for collecting a substance from blood or tissue, the probe system (1) comprising:

-a tube (10) having at least one first duct (15a) and at least one second duct (15b), and

-a dialysis probe section (20) comprising a membrane (25) and a sampling area (30) formed within the probe section (20) connected to the membrane (25)

And the probe section (20) is adapted to be positioned in the body in such a way that the membrane is dialytically connected in blood or tissue, and wherein the probe system (1) is adapted to feed perfusion fluid to the sampling region (30) via the first tubing (15a) at a feed flow rate, wherein the reinforcing fibers (100) are positioned within the second tubing (15b), characterized in that the probe system (1) is adapted to return perfusion fluid from the sampling region (30) via the second tubing (15b) at a return flow rate, wherein the return flow rate is higher than the feed flow rate and is defined by the reinforcing fibers (100) located within the second tubing (15 b).

2. The probe system (1) according to claim 1, characterized in that the reinforcement fiber (100) is a tube forming a third duct (110), and wherein the probe system (1) is adapted to return the perfusion fluid from the sampling region (30) via the third duct (110) at a return flow rate.

3. The probe system (1) according to claim 2, characterized in that said third duct (110) has a smaller cross-sectional flow area than said first duct (15a) and said second duct (15 b).

4. The probe system (1) according to claim 1, wherein the reinforcement fiber (100) is positioned in the second duct (15b) such that the perfusion fluid flows outside the reinforcement fiber, and wherein a return flow rate is defined by an outer diameter of the reinforcement fiber (100) relative to an inner diameter of the second duct (15 b).

5. Probe system (1) according to any one of the preceding claims, wherein the proximal end of the reinforcement fiber or tube (100) with respect to the probe section (20) is connected within the second duct (15b) at a proximal position with respect to the probe section (20) such that the probe system (1) can be inserted by pushing the reinforcement tube (100).

6. Probe system (1) according to claim 5, wherein the proximal end of the reinforcing fiber or tube (100) is fixed in a sealed manner to the inside of the second duct (15b) to prevent the fluid downstream with respect to the fixing member (55) from entering the area between the outside of the reinforcing tube (100) and the second duct (15 b).

7. Probe system (1) according to any one of the preceding claims, wherein the distal end of the reinforcing fiber or tube (100) with respect to the probe section (20) protrudes from an opening (16) in the outer wall (12) of the tube (10) at a position outside the body tissue.

8. The probe system (1) according to any one of the preceding claims, characterized in that the probe system (1) is adapted to conduct the perfusion fluid via the third conduit (110) for analysis.

9. Probe system (1) according to any one of the preceding claims, wherein the membrane (25) is positioned eccentrically on the tube (10), covering one or more openings formed in the outer wall (12) of the tube in the dialysis probe section (20).

10. Probe system (1) according to claim 9, wherein one such opening is formed over the entire circumference of the tube (10).

11. Probe system (1) according to any of the preceding claims, wherein the reinforcing fibers or tubes (100) are much more rigid than the tubes (10).