Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
  • A61B5/14525—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using microdialysis
  • A61B5/14528—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using microdialysis invasively
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M25/00—Catheters; Hollow probes
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
  • B01D61/24—Dialysis ; Membrane extraction
  • B01D61/28—Apparatus therefor
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes

Definitions

• 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 fluid for further analysis.
• Probe systems for collecting substances from, e.g., living tissue is disclosed in the publications US 5,191,900 and US 2011/0066103.
• Each comprises a supply and drainage line connecting to a dialysis probe section comprising a membrane and a sampling area, where the drainage line has a smaller cross area than the supply line (first conduit).
• the return flow rate is higher than the supply flow rate during use of the probe systems.
• the present invention further relates to a method of making such a micro dialysis probe in an easy and cost-effective manner.
• 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 advantageous for the micro-dialysis probe to have a sufficiently small diameter to fit into the smallest existing venous catheters, e.g. umbilical catheters for new-borns, and which occupies as small as possible a 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.
• 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 the blood or tissue, and where the probe system is adapted for a perfusion fluid to be fed to the sampling area via first conduit at a supply flow rate, wherein a reinforcing fiber is positioned within said second conduit, where 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 a cross area of at least one reinforcing fiber positioned within the second conduit such that the returned perfusion fluid flows in the area between the outside surface of the reinforcing fiber and the inner wall of the second conduit.
• a proximal end of said reinforcing fiber relative to the probe section may be connected to the inner surface of the second conduit at the proximal position relative to the probe section, thus enabling said probe system to be inserted by pushing the reinforcing fiber.
• At least two reinforcing fibres may be positioned in the second conduit.
• the number and possible individual cross areas of the fibres aggregate to occupy a desired part of the second conduit to calibrate the return flow rate.
• the return flow rate may be defined by the number of reinforcing fibres in the second conduit.
• All reinforcing fibres may be connected to the inner surface of the second conduit at the proximal position relative to the probe section, thus enabling said probe system to be inserted by pushing the reinforcing fiber.
• the proximal end of the reinforcing fiber/fibres may be fixed to the inner surface of the second conduit in a sealing manner which minimizes the area where fluid can flow and prevents fluid to pass the area behind the fixation in the direction of the flow between the outside surface of the reinforcing fiber/fibres and an inner surface/wall of the second conduit.
• the probe system may be adapted for said perfusion fluid to be directed to extracorporeal analysis via a third conduit.
• the membrane may be positioned eccentrically onto the tube covering one or more openings being 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 may be substantially more rigid than said tube to enable the handling of the probe without it buckling or breaking.
• the present invention further introduces a method to form a probe system for collecting substances from blood or tissue, the method including to form a probe system comprising:
• 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 be positioned intracorporeal with the membrane in dialysis connection to the blood or tissue
• the probe system is adapted for a perfusion fluid to be fed to the sampling area via the first conduit at a supply flow rate, and for the perfusion fluid to be returned from said sampling area at a return flow rate via the second conduit
• the method including to calibrate the return flow rate by positioning a reinforcing fiber within said second conduit such that the return flow rate is higher than the supply flow rate and is defined by a cross area of at least one reinforcing fiber positioned within the second conduit such that the returned perfusion fluid flows in the area between the outside surface of the reinforcing fiber and the inner wall of the second conduit.
• the method may include to calibrate the return flow rate by the number of reinforcing fibres in the second conduit.
• the method may include for a proximal end of said reinforcing fiber relative to the probe section to be connected to the inner surface of the second conduit at the proximal position relative to the probe section, thus enabling said probe system to be inserted by pushing the reinforcing fiber.
• the proximal end of the reinforcing fiber/fibres may be fixed to an inner surface of the second conduit in a sealing manner which minimizes the area where the fluid can flow and prevents fluid to pass the area behind the fixation in the direction of the flow between the outside surface of the reinforcing fiber/fibres and an inner surface/wall of the second conduit.
• 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 fiber.
• Fig. 4 Illustration of a second section of the dialysis probe system according to an embodiment, where a reinforcing fiber 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.
• 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.
• the membrane (25) allows substances of interest, such as glucose, to pass, while sampling fluid flowing in the flow channels is prevented from passing.
• 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 as possible a part of the cross section of the venous catheter.
• venous catheters e.g. umbilical catheters for new borns
• the probe section (20) it is formed by 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 EP2257215.
• the present invention is not limited to a construction as disclosed in figures 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.
• 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.
• 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.
• the proximal and distal ends of the probe system (1) are defined as the same ends as the proximal and distal ends of the multi-tube (10), respectively.
• 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.
• 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.
• 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 reinforcing fibres (100) positioned within the second conduit (15b).
• the embodiment shows three reinforcing fibres (100), any number could be inserted, as it will be explained later.
• the present invention includes at least one reinforcing fiber (100).
• a sampling 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 fed 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 reinforcing fiber (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 ensures, e.g., that no damage is made, and eases the comfort, whereas the stiffer (relative to the tube (10)) inner reinforcing fiber (100) assists as one function in having the probe system (1) inserted.
• a proximal end of reinforcing fiber (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).
• connection (55) is such that when pushing the reinforcing fiber (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.
• advantage of the reinforcing fiber (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 precisely as possible, but also since undesired chemical reactions may occur that would influence the measurements.
• 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 one or more reinforcing fibres (100) according to the actual requirements.
• 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 second conduit (15b), where the return flow rate is higher than the supply flow rate.
• the calibration of the return flow rate then can made by the number of inserted reinforcing fibres (100).
• the basic is the free flow path formed between the outside surface of the inserted reinforcing fibres (100) and the inner wall of the second conduit. Adding further reinforcing fibres (100) increases the aggregate fiber (100) cross area and thus reduces the free flow path to increase the flow rate.
• the reinforcing fiber (100) is fixed (55) to the inner surface of the second conduit (15b). This could be by glue or other fixing materials to connect the parts and having a sealing effect.
• the end-sealing and fixation elements (55) are biasing elements positioned at the circumference of the reinforcing fiber (100) fixing it by friction.
• the fixations (55) ensure that by pushing, dragging or pulling the reinforcing fiber (100), the rest of the probe system (1) naturally follows, thereby reducing the tendency to buckle or break.
• 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 fiber (100).
• a distal end of the reinforcing fiber (100) (distal relative to the probe section (20)) reaches out of an opening (16) in the external wall (12) of said tube (10) at an extracorporeal position outside the body, thus making it available to the operator.
• 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).
• a single opening is formed at the full circumference of the multi-tube (10).
• the rigidity, or stiffness, of the probe section (20) is formed exclusive by the reinforcing fiber (100), any internal separation wall (14) being fully removed in this section, whereas in another embodiment it supports an 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).
• the return flow rate is defined by the cross area of the reinforcing fiber (100) relative to the inner diameter of the second conduit (15b).
• the calibration of the return flow rate is made by inserting a plural of reinforcing fibres (100) with different cross areas to obtain a desired aggregate cross area.

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• 2021
  • 2021-05-12 DK DKPA202100497A patent/DK181117B1/en not_active IP Right Cessation
• 2022
  • 2022-05-06 EP EP22728145.8A patent/EP4337094A1/de not_active Withdrawn
  • 2022-05-06 WO PCT/EP2022/062277 patent/WO2022238252A1/en not_active Ceased

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