CA2191303A1 - Microdialysis probes and methods of use - Google Patents
Microdialysis probes and methods of useInfo
- Publication number
- CA2191303A1 CA2191303A1 CA002191303A CA2191303A CA2191303A1 CA 2191303 A1 CA2191303 A1 CA 2191303A1 CA 002191303 A CA002191303 A CA 002191303A CA 2191303 A CA2191303 A CA 2191303A CA 2191303 A1 CA2191303 A1 CA 2191303A1
- Authority
- CA
- Canada
- Prior art keywords
- chamber
- probe
- semi
- wall
- proximal end
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
-
- 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, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14525—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis
- A61B5/14528—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis invasively
-
- 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
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1678—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes intracorporal
-
- 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
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
- A61M1/342—Adding solutions to the blood, e.g. substitution solutions
- A61M1/3424—Substitution fluid path
- A61M1/3427—Substitution fluid path back through the membrane, e.g. by inverted trans-membrane pressure [TMP]
-
- 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
-
- 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
- A61M25/0021—Catheters; Hollow probes characterised by the form of the tubing
- A61M25/0023—Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
- A61M25/0026—Multi-lumen catheters with stationary elements
- A61M2025/0036—Multi-lumen catheters with stationary elements with more than four lumina
-
- 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
- A61M25/0021—Catheters; Hollow probes characterised by the form of the tubing
- A61M25/0023—Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
- A61M25/0026—Multi-lumen catheters with stationary elements
- A61M2025/004—Multi-lumen catheters with stationary elements characterized by lumina being arranged circumferentially
Abstract
A microdialysis probe (20, 100) arranged to have a primary probe (24), e.g., an electrical probe, secured to it so that the microdialysis probe extends about and is concentric with the primary probe to enable the combined microdialysis probe and the primary probe to be extended as a unit through a common opening into the body (10) of a living being, whereupon the microdialysis probe (20) can be used for selective sampling and/or administration of dialyzable compounds in biological fluids from living tissue within the body of the being and the primary probe (24) can be used for some other function within the body of the being without appreciably injuring adjacent tissue. The microdialysis probe (20) comprises a tube (22, 106) having a lumen therethrough for releasably mounting the primary probe, and at least one dialysis chamber (26, 118, 120). In one embodiment only a single annular dialysis chamber (26) is provided with the lumen (22) mounting the primary probe (24) extending therethrough. In another embodiment two semi-annular dialysis chambers (118, 120) are provided adjacent each other with the lumen (106) mounting the primary probe (24) extending therethrough. In either case each dialysis chamber comprises a wall (34, 122) formed of a semi-permeable material, an inlet passageway (28, 130) to the chamber (38, 118) and an outlet passageway (30, 140) from the chamber (32, 120).
Description
W095l32746 2 ~ 91 3~3 r~ .. J78l MTCROnTAT Y.~ [S PROBES AND ~TT~I-DS QF USE
SPErTT~'ICATION
T~ (;YI~NL~ OF TUT` INVFNTION
This invention relates generally to invasive medical devices and more particularly to flexible inD~L ~ designed to enter the living tissue to make meaDuL~ ~s, deliver drugs and/or selectively sample or alter the rh~m;rAl environment for analysis inside or outside of the body, and more particularly to a microdialysis probe suitable for connection to another primary probe to be extended through a common opening into the body of a living being.
Biological fluids contained in the interstitial space of tissues are often sampled for research and diagnostic ~uL~oses.
Also, it is often required that the rh~m;r,Al composition of the interstitial space be altered via rhArr- -r,lo~; c:~ 1 or physiological means. Microdialysis, which employs an invasive semip~ - - hle ~ e at the end of two open ducts makes it pOc ;hle to selectively sample or deliver low molecular weight Dul ~ ;es to the interstitial space.
In United States Letters Patent No. 4,694,832 (Ungerstedt) there i5 ~l;crlo~c~d a method for b~ ;n~ a dialysis probe intended for insertion in biological tissues, for example brain tissue, containing a dialysis membrane and ducts for flow of the perfusion fluid over the r ' r..e, and containing DU~UL ~5 for the membrane and ducts. The probe described requires the existence of a support structure for the ducts and membrane, and thus requires its own entry port and pI~-luces its own track or laceration of the tissue as it rl~-ccPn~c into the tissue being analyzed .
In United States Letters Patent No. 5,191,900 (Mishra) there is disclosed an alternate method of fabrication of a dialysis probe, which makes use of a U-shaped loop that uses an internal, biologically inert wire combined with i nt~rn~ 1 hydrostatic ~JLe:DDULe to Cupport the dialysis membrane and ducts. Alternative side-by-side and .~ C~l.-Lic probe configurations are also described, which exploit similar pr;nr;rl~c for support of the dialysis membrane and ducts. The Mishra '900 patent thus wossl3z746 2 ~ 9 7 ~93 P~ sr ,~l ~
describes a dialysis probe which also requires its own entry port and/or the making of a separate track or laceration to enter the tissue which is to be analyzed.
As will be appreciated by those skilled in the art the use of the probes of the above two patents require the dedication of an entry port and/or the creation o~ a track or laceration for the dialysis probe itself. Thus, if either of these probes is to be used with another probe, i.e., a primary probe of a different ty-pe, e.g., an electrical probe, two bores will have to be provided in patient's skull, one for each probe. These limitations may be minor hil.dL~ ces in some cases, e.g., blood lin~, or may be prohibitive in other cases, e.g., brain surgery, since the brain is not capable o regenerating injured or de~Lvy.:d tissue. Moreover, these limitations apply whether the probe is to be used for analytical/diagnostic ~-uL~oses or for therapeutic ~uL~oses. Thus, while the microdialysis probes of the above mentioned patents are suitable for their intended es they leave something to be desired from the st~nllroint of fllnrt;-~nAl ity.
Other probes are ~ close~ in United StatQs Letter6 Patent Nos. 4,903,707 (Kunte), 4,931,049 (Klimas) and 5,106,365 (H~rni~n~lDz) .
Since the present commercially available microdialysis probes u~e a dedicated port of entry, they suffer from another dislsdv-nt2lge in order to be useful for cl ~nlc~l yuL~ose~; they can only be used in their miniature versions which are intended to be used primarily in rodents. The maximum surface areas and flow rates they allow coupled with the present analytical E~ensitivities limit their use for 1 ;n~ only; that too with a poor temporal resolution. The existing microdialysis probes allow very low $10w rates t0.5 to 5 ul per minute) in order to achieve rD~nn;~hly high (5% to 30%) efficiency of capture of tissue analytes. This low rate is required because otherwise, there is a non-negligible depletion from the small amount o~
tissue ~uLLuul-ding the dialysis probe. Since preceding designs of dialysis probes have surface areas of about 3 . 8 mm2, there is a 8mall amount o~ tis6ue surface to cope with the flow volume.
wo ss/32746 2 1 9 1 3 ~ 3 r~ 5~ 78l In the exi6ting devices, typically, dialysates are collected at a flow rate of 0.5-5 ul/min for 10-60 min and then analyzed. The low collected quantities of these rh~m;oAl are insufficient for any on-line analysis in real time for most interstitial rh~7mir~1~. Cu..z,~.L~,- .ing the prior art probes in relatively larger ~ innC would eliminate some of these problems but the most common application of microdialysis being in brain tissue, having a laceration of larger magnitude in the brain to achieve these goals represents a major disadvantage, at least until there is a ~ LL.Ited evidence of any i _~ in patient outcome associated with the use of these probes.
It should be noted that there is a suggestion in the prior art to the use of a microdialysis probe joined with another c e~t for performing microdialysis and another function via a common entrance port. For example, in an article entitled Nodified Microdialysis Probe For Sampling Extrac~ r Fluid And Administering Drugs In Vivo, by G. Yadid, R Pacak, I.J. Kpoin, and D.S. Goldstein, appearing in American Journal Of Physiology, Volume 265,_1993, pages R1205-R1211, t~ere is disclosed a microdialysis probe havlng a cannula glued to its external surface to enable the administration of a rh~~cological agent, glycine, through the cannula to evaluate the behavioral effect thereof on the subject, e.g., cnncciol~c rats.
In an article entitled Combined Intracerebral Microdialysis And Ele.;~L u~hy~inl o~i o~1 Recording: Nethodology and Applications, by T.P. OLLel.~,vitch, D.A. Richards, G.S. Sarna, and L. Symon, in the Journal Of ~- ,s-i~nce Nethods, Volume 47, pages 139 - 145, 1993, there is diclosed a microdialysis probe ;nrl~ n~ in its housing a chlorided silver wire electrode for eleoLLu~.~.y~iolûgical recording. That probe also only needs a single access port. The ele-_~L~I.y iological mea~uL~ ~6, e.g., EEG and DC potentials, are obtained by the device by measuring the potential between its chlorided silver electrode and a remotely placed Ag/AgCl reference electrode.
As should be appreciated by those skilled in the art the microdialysis probes tl i col9secl in the two above - inn~
articles are integrated devices, that is the probe and the other wo 9sl32746 4 ~ ), S C 781 ~ t, be it a cannula or an Qlectrode, are p-~nr-n~ntly secured to the probe and form a part of the probe. Hence, such devices are o~ limited utility and cannot be used for a wide variety of applications. Moreover, the in~d structures are somewhat bulky and could result in excessive damage to adj acent tissue upon the introduction thereof into the being's body, e.g., the brain. Thus, a need still exi~:ts for a combination microdialysis probe and a primary probe of any type, and which combination will not result in excessive damage to adjacent tissue .
O~EC~ ~ OF ~ INVENTION
Accordingly, it is a general object of this invention to provide a microdialysis probe and method of use which overcomes the disadvantages of the priQr art.
It is a further object of this invention to provide a combined microdialysis probe and a primary probe of any suitable type 60 that only a relatively small, single entry port neQd be provlded lnto the patient's body for the microdialysis probe and the associated primary probe.
It is a further object of this invention to provide a micro-dialysis probe which is ~Ul, LLu.i~ed to releasably receive any one of various types of other primary probes 80 that the microdialysis probe extQnds col.ae..LLically about the primary probe, ~.heleu~ull only a small, single entry port need be provided into the patient's body for the i--LL~ n of the microdialysis probe and the primary probe.
SIlMMARv ûF q~ INVENTION
These and other ob; ects of this invention are achieved by providing a microdialysis probe arranged to have a primary probe secured to it 80 that the microdialysis probe extends about and is a~l~c.".LLic with the primary probe to enable the combined microdialysis probe and the primary probe to be extended as a unit through a common opening into the body of a living being, whereupon the microdialysis probe can be used for selective ~iampling and/or admlnistration of dialyza~le '- in biological fluids from living tissue within the body of the being wo ss/32746 ~ 1 9 ~ 3 0 3 r~ ,sr 781 and the primary probe can be used for some other function within the body of the being without appreciably injuring adjacent tissue .
The microdialysis probe comprises lumen means for mounting, e.g., releasably mounting, the primary probe to it, a dialysis chamber having a wall formed of a semi p~ hle material having a pore size larger than the -lec1llAr weight of the dialyzable '-, an inlet pA~s~oway to the chamber and an outlet pA ~:~a ~ y f rom the chamber .
The dialysis chamber is elongated and has a longitudinal axis, a distal end portion and a proximal end portion. The lumen has a longitudinal axis extending parallel to the axis of the dialysis chamber and is sized to A- - 'Ate the primary probe therein .
In accordance with one aspect of this invention the dialysis chamber is of annular shape and has an inner cylindrical wall which forms the primary probe receiving lumen. The outer wall of the dialysis chamber is formed of the semi-permeable material.
In accordance with another aspect of this invention the microdialysis probe comprises a pair of dialysis nh: ' ~~ D. Each of the rh: ' '] . has an outer wall formed of a semi p~ - hl~
material and respective inlet and outlet pA~ r, _YD coupled to the interior of respective ones of the pair of rh: ' ~ . Each of the dialysis rh~ ' 'c. is elongated and of semi-annular shape having a longitudinal axis, a distal end portion and a proximal end portion. The means for mounting the primary probe to the microdialysis probe comprises a common lumen having a longitudinal axis extending parallel to the axes of the two semi-annular chambers, with the common lumen being sized to te the primary probe therein.
D~SCRIPTION OF THE D~AWTNr.c Other objects and many attendant feaLuLcs of this invention will become readily appreciated as the same becomes better - understood by refe~ence to the following detailed description when cnn~id~red in connection with the a nying drawings wherein:
w0 95l32746 2 1 9 ~ ~ [) 3 r~ 78l --Fig. 1 i6 a side elevational view, not to scale, showing one ~ ' -'ir L of a microdialysis probe ~u..DLLuuLed in accordance with this invention extending through a single entry port in the skull so that the microdialysis chamber and the primary probe are both located within the brain of a living being;
Fig. 2 is a greatly enlarged ; cl ic view, partially in section of the distal end of the ~ of a microdialysis probe shown in Fig. l;
Fig. 3 is a sectional view taken along lines 3-3 of Fig. 2;
Fig. 4 is a view similar to that of Fig. 2 but showing the distal end of an alternative: ' '; L of a microdialysis probe cv..aLLu~ Led in accordance with this invention; and Fig. 5 is a ~e~tionAl view taken along lines 5-5 of Fig. 4.
nT~ TTT~n DE~r~TPTION OF TT~ ~K~ KK~ DIM~
Referring now to the various figures of t_e drawing wherein like re$erence characters refer to like parts, there i8 shown at 20 in Fig. 1, one: ~ t of a microdialysis probe c;u..~LLu. Led in accordance with this invention shown in position -Yt-~n~ling through the skull 10 of a person so that the distal end of the probe is located within the per60n's brain 14. In Figs. 4 and 5 there is shown the distal end of another microdialysis probe 100 (to be described later. This alternative probe is Arr to be used in the same manner as probe 20.
It should be pointed out at this juncture that the most eminent use of microdialysis probes ~o"tiLLu.;Led in accordance with this invention is in sampling and or altering the chc~m;cal environment of the brain. Thus, the probe 20 is shown in an exemplary position passing through a conv~n~;onAl access port 12 in the skull 10 and into the brain 14. Xowever the probes 20 and 100 may also be used for similar ~uLyoses in other tissues or tissue matrices of the body. In particular, the probes 20 and 100 can be used for ~ l;ng the nh~;r~l environment of blood, muscle, skin, amniotic fluid, and other organs and . ~ ~s of the body. To that end, the probes 20 and 100 are ArrAn~e~ to allow the illLLv~ nn of ~ '- of low -olerlll Ar weight in the ~pec;fir sites of the tissue while collecting samples, and Wog~/32746 2 1 9 1 3 0 3 .I,L~ ~J~781 thus enable monitoring the effects produced by the substance il~L~ud-lced in the fully interactive living biological system.
As can be seen in Figs. 2-3, the probe 20 basically comprises an elongated central tube 22 which is arranged to receive in its central p~a y or lumen any type of primary device, e.g., a primary probe 24, such as an indwelling catheter, a biopsy needle, an intercranial ~LasnuLe monitor, or an electrophysiological probe, to have access to the specific internal ~ite at which the microdialysis probe 20 will be located. The tube 22 is constructed of a biologically inert plastic or other similar material, such as polyamide or polyester, that is strong enough to a~ te the range of fluid pressures that the circulating dialysis solution may exert, at ~LLL~ -ly thin wall configurations.
An annular dialysis chamber 26 is mounted on the distal end of the central tube 22. At least one fluid inlet tube 28 and at least one fluid outlet tube 30 icate with the interior 32 of the dialysis chamber. The dialysis chamber includes a cylindrical outer wall 34. This wall i6 made up of semi-p, --hle ~ al~e having a pore size larger than the - lec~ r weight of the dialyzable ~ '~. The 5emi r --hle .I.~e extends c~ P~ ~ ~ically about and somewhat close to the outer periphery of the distal end of the central tube 22 to form the dialysis chamber tl-eL~b~L..__... The fluid inlet tube comprises an elongated tube whose external dii tDr is just slightly less than the thirl~n~8 of the annular dialysis chaDber. The fluid outlet tube also comprises an elongated tube whose external diameter is just slightly less than the thir-bn~ of the annular dialysis chamber.
As can be seen in Fig. 3 the distal end portion of the inlet tube 28 extends along the outer surface of the central tube 22 parallel to the longitudinal central axis 36 thereof so that the inlet tube's open free end 28A is located within and closely adjacent the bottom or distal end 38 of the annular dialysis chamber and is in fluid i cation with the interior of the dialysis chamber. The distal end portion of the outlet tube 30 also extends along the outer surface of the central tube 22 wo gS/327~G 8 PCT/US95/06781 parallel to the longitudinal axis 36 but on the opposite side as the inlet tube 28 so that the open free ena 30A of the outlet tube is located within the dialysis chamh-er closely adjacent the top or proximal end 40 thereof and in fluid ic~tion with the interior of the dialysis chamber.
The proximal end 40 of the sQmi P~ -hle ' n~ of the dialysis chamber is f ixedly secured about its entire periphery to the outer surface of the immediately adjacent portion of the central tube 22 by means of any suitable adhesive or glue 42, e.g., epoxy or cryanoacrylate, extending between those surfaces.
The inlet and outlet tubes 28 and 30, respectively, pass through the adhesive 42 50 that their open ends are located within the dialysis chamber as described heretofore. The adhesive also serves to hold the inlet and outlet tubes in their desired positions therein.
In a similar manner the distal end of the semi r~ ~hle membrane of the dialysis chamber is f ixedly secured about its Qntire periphery to the outer surface of the central tube 22 by any suitable adhesive or glue 44 extending between those surfaces. As can be seen in Fig. 2, the adhesive or glue 44 is ~li cp~fi~A in a ring which includes an outer surface which tapers arcuately from the outer surface of the semi F -- - -hl ~ ,e until it merges with the tapering distal free edge 46 of the central tube 22. The tapering surface of the glue 44 ensures that tissue damage is kept to a minimum when the probe is inserted into the brain.
The inlet tube 28 crmr~ tc the dialysis medium, consisting of ingredients s~1ect~A either for minimal peL LuLLation of the ;rill environment, or consisting of _ '- added either for diagnostic, analytical, or therapeutic applications into the interior of the microdialysis chamber 32. In accordance with a preferred --ir L of this invention the entry and exit tubes 28 and 30, respectively, are made of polyamide, fused silica, or other materials consistent with the objectives of resistance to high internal and/or external pL~iULe~ small size, and biological inertness. Each tube is of sufricient length to reach outside of the tissue entry port. The inlet tube is preferably Woss/32746 2 1 9 1 303 P~ 78l attached to a liquid pump (not shown). That pump may be a mechanically driven syringe pump and is coupled to the inlet tube 28 with a luer-lock fitting (not shown), with or without adapters, such as polyethylene tubing. This arrangement enables the pump to deliver the microdialysis medium to the bottom of the microdialysis probe.
As can be seen clearly in Fig. 2, the distal end 28A of the entry tube 28 and the distal 30A of exit tube 30 are situated preferably farthest from each other in order to allow a maximum circulation of the fluid within the chamber 32. This action allows maximum efficacy of the solute ~yr~h~n~e. The direction of flow of the fluid through the tubes and microdialysis chamber is shown by the arrows in Figs. 2 and 3.
Both the entry and exit tubes 2 8 and 3 0 respectively, are selected and designed such that they pass through the access port 12 . That port may be any suitable conv~nt; nn~ 1. such as is available from various manufacturers, e.g., Camino I,aboratories, Inc., for the purpose of inserting the primary invasive device (s) through a common entry site. The exit or outlet tube 30 serves as the means to collect the microdialysis medium from the probe's chamber 32 once the analytes of interest have diffused across the dialysis ~lle, and thus serves as an egress for the microdialysis medium from the probe. To that end, the exit tube 30 is of such a length as to remove the microdialysate outside the tissue to a point where it can be cnl 1 ect~d.
The primary purpose of the central tube's lumen 22 is to serve as a passage for the releasable J i n~ of a primary invasive device e.g., a probe 24, or any other device (not shown). The central lumen can also be used to receive a rigid stylet (not shown) in the event that no primary device is intended for use. The inner diameter of the lumen can be fabricated either to fit tightly li.e., press fit) or loosely - (i.e., slip-fit) the primary invasive device. When the lumen is sized to allow the slip-fitting of the primary devices therein, the depth of penetration of the microdialysis probe 20 and the primary probe or device 24 can be ~n~r~nd~ntly adjusted.
wossl32746 - 2 ~ 03 F~~ 5.~ 78l --In some instances the central tube 22 may replace the sheath that is uDed to protect the delicate cable or equivalent of the primary invasive device. In these circumstances, the cable of the primary invasive device would be conci~lpred ~s primary invasive device.
~ he semi-p~- --hl e membrane serves the primary function of creatlng a fluid compartment within the fluid matrix of a tissue, such as brain, and allows only passive diffusion of small molecular weigh solutes across its pores. To that end the micro-dialysLs ~ e may be made from Le~ elc.ted cellulose and having a permeability limit such as 6000 Dalton. With this material molecules with ~ c~ r weight greater than 6000 Dalton will not pass therethrough, whereas molecules of less than 6000 Dalton will pass therethrough. Other materials besides e~el el~ted cellulose may be used, and other cut-offs different from 6000 Dalton may be used, to permit the dialysis of --leclllec of different ---lecl~l Ar species. However, it is imperative that the dialysis membrane used must be capable of withstanding ~L~DUL~S created by fluid flow within and ~Lesau-e exerted by the tissue environment, such as intracranial fluid. Regenerated cellulose membranes are used in the preferred ~ L since such materials will withstand ~ eSDULe:S up to 610 mm ~g, approximately three times higher than the highest intracranial ~:eDDUL~:: to be encountered.
The central tube 22 may be of any suitable length 80 that its top edge 48 (Fig. 2~ is located adjacent the entry port 12 through the skull. In accordance with a preferred -'i- : of the invention, the inlet and outlet tubes 28 and 30 extend along and are secured to the outer surface of the central tube 22 by se~uL~ means, e.g., an adhesive, (not shown). This arrA, - I_ ensures that the inlet and outlet tubes do not cause damage to adjacent tissue, as could occur if the probe 20 was extended through an arcuate path or track into the brain. In such a case, if the inlet and outlet tubes did not extend along the central tube they could take a different track through the brain than the central tube 22 thus ~i~r-gin~ adjacent tissue.
Wo 9S13274G 2 1 q ~ 3 0 3 PCT/US9S/06781 In Figs. 4 and 5 there is shown the distal end of the alternative ' - ' i L 100 of a microdialysis probe of thi6 invention. The probe 100 includes two microdialysis rh~ D to permit simultaneous perfusion of the two chambers under different conditions, e.g., flow rate, medium composition. ThuD, one dialysis function, e.g., a diagnostic $unction, can be carried out in one chamber, and a second dialysis function, e.g., a therapeutic function can be carried out in the other chamber at the same time.
The probe 100 ~ir~l ly comprises a dual walled tube 102 having an outer wall 104 and an inner wall 106. The tube 102 is preferably formed of the same material as that of the tube 22 of the probe 20 described heretofore. The inner wall 106 includes a central p~cF?, _y 108 extending throuqh it for receipt of the primary probe 2 4 .
As can be seen clearly in Fig. 5, four p~ccRs~ _yD 110, 112, 114, and 116 extend through the dual walled tube 102. Each of the r~Cca~J _y~ extends for approximately ninety degrees of the circumference of the dual walled tube. The p:~cs~, _YD 110 and 112 from the inlet and outlet, respectively, to a first microdialysis chamber 118, while the p~cca~ yD 114 and 116 from the inlet and outlet of the second microdialysis chamber 120.
The microdialysis rh: ~~ D 118 and 120 are each semi-annular in shape and are formed by a common cylindrical outer wall 122 of the same semi r ~ -hle material as the outer wall 34 of the probe 20. The cylindrical outer wall 122 extends 4...,.~C-.,I ically about the outer wall 104 of the dual walled tube 102, and is spaced slightly therefrom to define the two rh~ ' ~~ D 118 and 120 theLebe~ . The outer wall 122 is secured in place about its top peripheral edge 124 by a ring of glue 126 of the same compo6ition as that described heretofore. In a similar manner the bottom peripheral edge 128 of the s~ni,-- --hle - ' ~ e outer wall 122 is secured in place by a ring of glue 130, which is also of the same composition as that described heretofore.
The dual walled tube 102 includes a pair of longit~Ainllly extending ribs 132 and 134 (Fig. 5) projecting out of the outer surface of the dual walled tube 102. These ribs are located _ _ _ _ _ W09~327.~6 21 9 1 3()3 E~l/~8, ~C 781 --diametrically opposite each other, with rib 132 being located at the interface of pAI f~A5__ YD 110 and 114 and with rib 134 being located at the interface of passageways 112 and 116. The ribs are each of a height es,,ual to the distance separating the inner surface of the SC~1n;rP ~~hle outer wall 122 and the outer surface of the dual walled tube so that they divide the space between the outer wall 122 and the dual walled tube into the two semi-annular chambers 118 and 120.
The bottom of each of the p~sa, _YD 110, 112, 114 and 116 is sealed by a plug of glue 136 of the same type as described earlier . The top of each of the pA--a jeways terminates in a conduit. In particular, the inlet pA4~ a~J~IAAy 110 to microdialysis chamber 118 terminates in a conduit 138 while the outlet pA~Iag y 112 to that chamber terminates in a conduit 140. In a similar manner the p~C:sal,_ yD 114 and 116 to and from the other microdialysis chamber 120 terminate in respective conduits (not shown).
The pA~a, _y 110 ~ icateS with the bottom of the microdialysis chamber 118 via a plurality of holes or apertures 142, while the pAR~ y 112 1 ~Aates with the top of that microdialysis chamber via a plurality of holes or ~eL~u~-s 144.
Thus, a microdialysis medium may be pumped from a pump (not shown) cnnn~ct~ to the inlet conduit 110, ..l.aLe:U~UI- that medium will flow through the inlet conduit 138 into the ;cAting pA~Aa~_ _y 110 through the a~ LUL~I3 142 into the bottom of the microdialysis chamber 118, through that chamber out of the ap~LLuL~s 144 into the pA~as _y 112 and from there through the outlet conduit 140 in the direction of the arrows shown in Fig.
4. Another microdialysis medium may be pumped from another pump (not shown) into the inlet conduit cnnn~rtc~ to rAAa~ y 114 to the microdialysis chamber 120 in a similar manner. That medium will then pass out of the chamber 120 into the pas__, _y 116 and the i iA~ting outlet conduit.
As should be appreciated by those Dkilled in the art, the microdialysis probe 100, in addition to providing a pair of microdialysis chambers 118 and 120, also provides for the LLa~lD~UL L of the dialysis medium to and from those chambers via -W09~l32746 2 1 9 ~ 3~3 F~~ 81 internally located pAI ~ageways~ i.e., the pA~A~, _yb in the dual walled tube 102. That dual walled tube can be readily fabricated, e.g., ~xLLuded from any suitable material, e.g., polyester, polyamide or TEFLON~.
It should be pointed out at this juncture that a micro-dialysis probe can be c.,..DL.u~ Led to incoL~L,.~te more than the two microdialysis rh: ' ~Q shown in the ~ L 100.
As should now be appreciated by those skilled in the art, the probes 20 and 100 of this invention provides an additional capability, namely, microdialysis, to the capability of the primary device with minimal increase in diameter over that of the primary device. Further still the probes 20 and 100 do not require an inr~ c, L access port other than port 12, or make a separate track or laceration through the tissue being sampled, analyzed or treated. Thus, the subject invention eliminates most, if not all, of the problems the prior art set ~orth above and offers much greater adaptability in order to be suitable for several possible applications.
In accordance with one preferred : - ' i - - of this invention, the microdialysis probes 20 and 100 are sufficiently small, e.g., have an external diameter of 4 mm and a length of at least 30 mm, to enable each to be a~ Led within a conv~-ntirmAl skull access port, giving a surface area of 377 sS~uare mill~r t~r-:. This area is approYimately 100 to 300 times greater than the prior art dialysis prob{~s. Accordingly, microdialysis probes c-...DLLu~;Led in ~ccc,Ldal.c2 with this invention can provide a flow rate approaching 100 ul/minute without sacrificing ef~iciency or adversely depleting interstitial space of rhPm~CAl~ needed for r~nt~in;n~ tissue viability .
Some ~ lAry advantages of such a c~nfig~ration are: In a situation where only partial sampling of interstitial rhQmic~l~
is desired and larger dQpletion of these ~ ;CA1~ is unde6irable, one can use ~XLL~ -ly low flow rates (1-4 ul/min) achieving 80-10096 efficacy. The illL e~Ded surface area of the probes 20 and 100 also translate into a r~ lr-tinn in variability, over time and from patient to patient, because of the greater _ _ _ _ _ _ _ _ _ _ _ wo 95/32746 2 1 9 1 3 0 3 r~ 7 e 1~781 amount of tissue which is sampled. In a situation where a fast depletion of endogenous toxins is desired, a very high flow rate can be used ~y properly nhnnc;ng the ~nnfi~lration. For example, the probes 20 or 100 may be used to remove water, in the case of edema, by dialyzing a hypertonic Dextran solution Or a ~ clllAr weight of 100,000 Dalton, or to remove ammonia, in the case of acute liver failure. In these therapeutic applications, it is pos~;ihle to Du~eLruse at significantly higher flow rates, e.g., 1 ml/min or higher. This means that greater amounts of toxic substances can be removed from the tisque when the patient's vasculature is unable to do so, e . g ., becau8e of pathnl o~; n2l 1 1 y high intracranial pL~ ULe which pinches shut the venous outflow, or because of pathologically high levels of ammonia in the blood.
In a setting where a rh2~rr-retltical agent is to be dialyzed out, a greater surface area can be exposed at low, medium or high flow rate, rlc-p~n~inq on whether or not a simultaneous sampling of its erfects on interstitial chemistry is desired. The cl, - l ation of the infused drug can be easily adjusted and adapted according to f low rate to get the maximum therapeutic advantage. All of these advantages are obtained ~rom a larger _ize dialysis probe, without any significant i~crease in the amount of tissue damage over the size of the primary probe.
The primary probe, with which the microdialy6is probes 20 and 100 of this invention can be used, can comprise any conventional device, such as an intracranial ~e6auL~ probe, an eleo~Lu~llyDiological recording electrode, standardized 1- ,2 R~F'hl~
surgical ir~-L~ (e.g., a spinal needle, ~uch as a luer-lock syringe tip or cannula, usually having a beveled and sharp tip), etc. ~I'L~UV~L~ it is poss2hle to easily adapt the microdialysis probe described here to multiple types of primary probes, the ~1-'2 2 t~r of the primary probe being the only parameter of significance to change, from the p_~Dl.e-;~ive of the microdialysis probe. In cases where no primary probe is intended for use, a li~LU~;LU ~, such as a stylet or a beveled cannula, may be selected based purely on cnnR~2~C~rations for delivery (cutting or blunt, flexible or rigid, plâstic or steel), and can be obtained W0 95l32746 2 1 9 1 3 0 3 ~ 78l ec ; r;~l 1 y and readily, to be u8ed as the primary probe for delivery purposes.
As should be appreciated from the foregoing the subject invention provides a microdialysis probe which can use, either simult~neo~lcl y or i ntlDrDrl~Dntly~ the same entry and passage as that used by other invasive devices; thus m;nimi ~:in~ or eliminating an increased possibility of infection due to use of the microdialysis probe, and minimizing or eliminating increased tissue damage caused by the physical insertion of the probe is described. Thus, the subject invention provides the clinician or scientific researcher with a means of performing microdialysis via a single entry passage in the body along with u6e of one or more other invasive device6. This aLL~ 1 of microdialysis probe with other invasive devices offers maximal flexibility in logistic terms , i . e ., the potential to stock primary probes separately from microdialysis probes and use the combined configuration at the phy6ician'6 option; and to adjust the depth of the two probes in~DpDn~Dntly. Most importantly, it offers methods for sampling and theri~re~ltirAlly modifying the rhDmi~
environment of tissue with minimal invasiveness.
Without further elaboration, the foregoing will so fully illustrate our invention that others may, be applying current or future knowledge, adopt the 6ame for use under various conditions of service.
SPErTT~'ICATION
T~ (;YI~NL~ OF TUT` INVFNTION
This invention relates generally to invasive medical devices and more particularly to flexible inD~L ~ designed to enter the living tissue to make meaDuL~ ~s, deliver drugs and/or selectively sample or alter the rh~m;rAl environment for analysis inside or outside of the body, and more particularly to a microdialysis probe suitable for connection to another primary probe to be extended through a common opening into the body of a living being.
Biological fluids contained in the interstitial space of tissues are often sampled for research and diagnostic ~uL~oses.
Also, it is often required that the rh~m;r,Al composition of the interstitial space be altered via rhArr- -r,lo~; c:~ 1 or physiological means. Microdialysis, which employs an invasive semip~ - - hle ~ e at the end of two open ducts makes it pOc ;hle to selectively sample or deliver low molecular weight Dul ~ ;es to the interstitial space.
In United States Letters Patent No. 4,694,832 (Ungerstedt) there i5 ~l;crlo~c~d a method for b~ ;n~ a dialysis probe intended for insertion in biological tissues, for example brain tissue, containing a dialysis membrane and ducts for flow of the perfusion fluid over the r ' r..e, and containing DU~UL ~5 for the membrane and ducts. The probe described requires the existence of a support structure for the ducts and membrane, and thus requires its own entry port and pI~-luces its own track or laceration of the tissue as it rl~-ccPn~c into the tissue being analyzed .
In United States Letters Patent No. 5,191,900 (Mishra) there is disclosed an alternate method of fabrication of a dialysis probe, which makes use of a U-shaped loop that uses an internal, biologically inert wire combined with i nt~rn~ 1 hydrostatic ~JLe:DDULe to Cupport the dialysis membrane and ducts. Alternative side-by-side and .~ C~l.-Lic probe configurations are also described, which exploit similar pr;nr;rl~c for support of the dialysis membrane and ducts. The Mishra '900 patent thus wossl3z746 2 ~ 9 7 ~93 P~ sr ,~l ~
describes a dialysis probe which also requires its own entry port and/or the making of a separate track or laceration to enter the tissue which is to be analyzed.
As will be appreciated by those skilled in the art the use of the probes of the above two patents require the dedication of an entry port and/or the creation o~ a track or laceration for the dialysis probe itself. Thus, if either of these probes is to be used with another probe, i.e., a primary probe of a different ty-pe, e.g., an electrical probe, two bores will have to be provided in patient's skull, one for each probe. These limitations may be minor hil.dL~ ces in some cases, e.g., blood lin~, or may be prohibitive in other cases, e.g., brain surgery, since the brain is not capable o regenerating injured or de~Lvy.:d tissue. Moreover, these limitations apply whether the probe is to be used for analytical/diagnostic ~-uL~oses or for therapeutic ~uL~oses. Thus, while the microdialysis probes of the above mentioned patents are suitable for their intended es they leave something to be desired from the st~nllroint of fllnrt;-~nAl ity.
Other probes are ~ close~ in United StatQs Letter6 Patent Nos. 4,903,707 (Kunte), 4,931,049 (Klimas) and 5,106,365 (H~rni~n~lDz) .
Since the present commercially available microdialysis probes u~e a dedicated port of entry, they suffer from another dislsdv-nt2lge in order to be useful for cl ~nlc~l yuL~ose~; they can only be used in their miniature versions which are intended to be used primarily in rodents. The maximum surface areas and flow rates they allow coupled with the present analytical E~ensitivities limit their use for 1 ;n~ only; that too with a poor temporal resolution. The existing microdialysis probes allow very low $10w rates t0.5 to 5 ul per minute) in order to achieve rD~nn;~hly high (5% to 30%) efficiency of capture of tissue analytes. This low rate is required because otherwise, there is a non-negligible depletion from the small amount o~
tissue ~uLLuul-ding the dialysis probe. Since preceding designs of dialysis probes have surface areas of about 3 . 8 mm2, there is a 8mall amount o~ tis6ue surface to cope with the flow volume.
wo ss/32746 2 1 9 1 3 ~ 3 r~ 5~ 78l In the exi6ting devices, typically, dialysates are collected at a flow rate of 0.5-5 ul/min for 10-60 min and then analyzed. The low collected quantities of these rh~m;oAl are insufficient for any on-line analysis in real time for most interstitial rh~7mir~1~. Cu..z,~.L~,- .ing the prior art probes in relatively larger ~ innC would eliminate some of these problems but the most common application of microdialysis being in brain tissue, having a laceration of larger magnitude in the brain to achieve these goals represents a major disadvantage, at least until there is a ~ LL.Ited evidence of any i _~ in patient outcome associated with the use of these probes.
It should be noted that there is a suggestion in the prior art to the use of a microdialysis probe joined with another c e~t for performing microdialysis and another function via a common entrance port. For example, in an article entitled Nodified Microdialysis Probe For Sampling Extrac~ r Fluid And Administering Drugs In Vivo, by G. Yadid, R Pacak, I.J. Kpoin, and D.S. Goldstein, appearing in American Journal Of Physiology, Volume 265,_1993, pages R1205-R1211, t~ere is disclosed a microdialysis probe havlng a cannula glued to its external surface to enable the administration of a rh~~cological agent, glycine, through the cannula to evaluate the behavioral effect thereof on the subject, e.g., cnncciol~c rats.
In an article entitled Combined Intracerebral Microdialysis And Ele.;~L u~hy~inl o~i o~1 Recording: Nethodology and Applications, by T.P. OLLel.~,vitch, D.A. Richards, G.S. Sarna, and L. Symon, in the Journal Of ~- ,s-i~nce Nethods, Volume 47, pages 139 - 145, 1993, there is diclosed a microdialysis probe ;nrl~ n~ in its housing a chlorided silver wire electrode for eleoLLu~.~.y~iolûgical recording. That probe also only needs a single access port. The ele-_~L~I.y iological mea~uL~ ~6, e.g., EEG and DC potentials, are obtained by the device by measuring the potential between its chlorided silver electrode and a remotely placed Ag/AgCl reference electrode.
As should be appreciated by those skilled in the art the microdialysis probes tl i col9secl in the two above - inn~
articles are integrated devices, that is the probe and the other wo 9sl32746 4 ~ ), S C 781 ~ t, be it a cannula or an Qlectrode, are p-~nr-n~ntly secured to the probe and form a part of the probe. Hence, such devices are o~ limited utility and cannot be used for a wide variety of applications. Moreover, the in~d structures are somewhat bulky and could result in excessive damage to adj acent tissue upon the introduction thereof into the being's body, e.g., the brain. Thus, a need still exi~:ts for a combination microdialysis probe and a primary probe of any type, and which combination will not result in excessive damage to adjacent tissue .
O~EC~ ~ OF ~ INVENTION
Accordingly, it is a general object of this invention to provide a microdialysis probe and method of use which overcomes the disadvantages of the priQr art.
It is a further object of this invention to provide a combined microdialysis probe and a primary probe of any suitable type 60 that only a relatively small, single entry port neQd be provlded lnto the patient's body for the microdialysis probe and the associated primary probe.
It is a further object of this invention to provide a micro-dialysis probe which is ~Ul, LLu.i~ed to releasably receive any one of various types of other primary probes 80 that the microdialysis probe extQnds col.ae..LLically about the primary probe, ~.heleu~ull only a small, single entry port need be provided into the patient's body for the i--LL~ n of the microdialysis probe and the primary probe.
SIlMMARv ûF q~ INVENTION
These and other ob; ects of this invention are achieved by providing a microdialysis probe arranged to have a primary probe secured to it 80 that the microdialysis probe extends about and is a~l~c.".LLic with the primary probe to enable the combined microdialysis probe and the primary probe to be extended as a unit through a common opening into the body of a living being, whereupon the microdialysis probe can be used for selective ~iampling and/or admlnistration of dialyza~le '- in biological fluids from living tissue within the body of the being wo ss/32746 ~ 1 9 ~ 3 0 3 r~ ,sr 781 and the primary probe can be used for some other function within the body of the being without appreciably injuring adjacent tissue .
The microdialysis probe comprises lumen means for mounting, e.g., releasably mounting, the primary probe to it, a dialysis chamber having a wall formed of a semi p~ hle material having a pore size larger than the -lec1llAr weight of the dialyzable '-, an inlet pA~s~oway to the chamber and an outlet pA ~:~a ~ y f rom the chamber .
The dialysis chamber is elongated and has a longitudinal axis, a distal end portion and a proximal end portion. The lumen has a longitudinal axis extending parallel to the axis of the dialysis chamber and is sized to A- - 'Ate the primary probe therein .
In accordance with one aspect of this invention the dialysis chamber is of annular shape and has an inner cylindrical wall which forms the primary probe receiving lumen. The outer wall of the dialysis chamber is formed of the semi-permeable material.
In accordance with another aspect of this invention the microdialysis probe comprises a pair of dialysis nh: ' ~~ D. Each of the rh: ' '] . has an outer wall formed of a semi p~ - hl~
material and respective inlet and outlet pA~ r, _YD coupled to the interior of respective ones of the pair of rh: ' ~ . Each of the dialysis rh~ ' 'c. is elongated and of semi-annular shape having a longitudinal axis, a distal end portion and a proximal end portion. The means for mounting the primary probe to the microdialysis probe comprises a common lumen having a longitudinal axis extending parallel to the axes of the two semi-annular chambers, with the common lumen being sized to te the primary probe therein.
D~SCRIPTION OF THE D~AWTNr.c Other objects and many attendant feaLuLcs of this invention will become readily appreciated as the same becomes better - understood by refe~ence to the following detailed description when cnn~id~red in connection with the a nying drawings wherein:
w0 95l32746 2 1 9 ~ ~ [) 3 r~ 78l --Fig. 1 i6 a side elevational view, not to scale, showing one ~ ' -'ir L of a microdialysis probe ~u..DLLuuLed in accordance with this invention extending through a single entry port in the skull so that the microdialysis chamber and the primary probe are both located within the brain of a living being;
Fig. 2 is a greatly enlarged ; cl ic view, partially in section of the distal end of the ~ of a microdialysis probe shown in Fig. l;
Fig. 3 is a sectional view taken along lines 3-3 of Fig. 2;
Fig. 4 is a view similar to that of Fig. 2 but showing the distal end of an alternative: ' '; L of a microdialysis probe cv..aLLu~ Led in accordance with this invention; and Fig. 5 is a ~e~tionAl view taken along lines 5-5 of Fig. 4.
nT~ TTT~n DE~r~TPTION OF TT~ ~K~ KK~ DIM~
Referring now to the various figures of t_e drawing wherein like re$erence characters refer to like parts, there i8 shown at 20 in Fig. 1, one: ~ t of a microdialysis probe c;u..~LLu. Led in accordance with this invention shown in position -Yt-~n~ling through the skull 10 of a person so that the distal end of the probe is located within the per60n's brain 14. In Figs. 4 and 5 there is shown the distal end of another microdialysis probe 100 (to be described later. This alternative probe is Arr to be used in the same manner as probe 20.
It should be pointed out at this juncture that the most eminent use of microdialysis probes ~o"tiLLu.;Led in accordance with this invention is in sampling and or altering the chc~m;cal environment of the brain. Thus, the probe 20 is shown in an exemplary position passing through a conv~n~;onAl access port 12 in the skull 10 and into the brain 14. Xowever the probes 20 and 100 may also be used for similar ~uLyoses in other tissues or tissue matrices of the body. In particular, the probes 20 and 100 can be used for ~ l;ng the nh~;r~l environment of blood, muscle, skin, amniotic fluid, and other organs and . ~ ~s of the body. To that end, the probes 20 and 100 are ArrAn~e~ to allow the illLLv~ nn of ~ '- of low -olerlll Ar weight in the ~pec;fir sites of the tissue while collecting samples, and Wog~/32746 2 1 9 1 3 0 3 .I,L~ ~J~781 thus enable monitoring the effects produced by the substance il~L~ud-lced in the fully interactive living biological system.
As can be seen in Figs. 2-3, the probe 20 basically comprises an elongated central tube 22 which is arranged to receive in its central p~a y or lumen any type of primary device, e.g., a primary probe 24, such as an indwelling catheter, a biopsy needle, an intercranial ~LasnuLe monitor, or an electrophysiological probe, to have access to the specific internal ~ite at which the microdialysis probe 20 will be located. The tube 22 is constructed of a biologically inert plastic or other similar material, such as polyamide or polyester, that is strong enough to a~ te the range of fluid pressures that the circulating dialysis solution may exert, at ~LLL~ -ly thin wall configurations.
An annular dialysis chamber 26 is mounted on the distal end of the central tube 22. At least one fluid inlet tube 28 and at least one fluid outlet tube 30 icate with the interior 32 of the dialysis chamber. The dialysis chamber includes a cylindrical outer wall 34. This wall i6 made up of semi-p, --hle ~ al~e having a pore size larger than the - lec~ r weight of the dialyzable ~ '~. The 5emi r --hle .I.~e extends c~ P~ ~ ~ically about and somewhat close to the outer periphery of the distal end of the central tube 22 to form the dialysis chamber tl-eL~b~L..__... The fluid inlet tube comprises an elongated tube whose external dii tDr is just slightly less than the thirl~n~8 of the annular dialysis chaDber. The fluid outlet tube also comprises an elongated tube whose external diameter is just slightly less than the thir-bn~ of the annular dialysis chamber.
As can be seen in Fig. 3 the distal end portion of the inlet tube 28 extends along the outer surface of the central tube 22 parallel to the longitudinal central axis 36 thereof so that the inlet tube's open free end 28A is located within and closely adjacent the bottom or distal end 38 of the annular dialysis chamber and is in fluid i cation with the interior of the dialysis chamber. The distal end portion of the outlet tube 30 also extends along the outer surface of the central tube 22 wo gS/327~G 8 PCT/US95/06781 parallel to the longitudinal axis 36 but on the opposite side as the inlet tube 28 so that the open free ena 30A of the outlet tube is located within the dialysis chamh-er closely adjacent the top or proximal end 40 thereof and in fluid ic~tion with the interior of the dialysis chamber.
The proximal end 40 of the sQmi P~ -hle ' n~ of the dialysis chamber is f ixedly secured about its entire periphery to the outer surface of the immediately adjacent portion of the central tube 22 by means of any suitable adhesive or glue 42, e.g., epoxy or cryanoacrylate, extending between those surfaces.
The inlet and outlet tubes 28 and 30, respectively, pass through the adhesive 42 50 that their open ends are located within the dialysis chamber as described heretofore. The adhesive also serves to hold the inlet and outlet tubes in their desired positions therein.
In a similar manner the distal end of the semi r~ ~hle membrane of the dialysis chamber is f ixedly secured about its Qntire periphery to the outer surface of the central tube 22 by any suitable adhesive or glue 44 extending between those surfaces. As can be seen in Fig. 2, the adhesive or glue 44 is ~li cp~fi~A in a ring which includes an outer surface which tapers arcuately from the outer surface of the semi F -- - -hl ~ ,e until it merges with the tapering distal free edge 46 of the central tube 22. The tapering surface of the glue 44 ensures that tissue damage is kept to a minimum when the probe is inserted into the brain.
The inlet tube 28 crmr~ tc the dialysis medium, consisting of ingredients s~1ect~A either for minimal peL LuLLation of the ;rill environment, or consisting of _ '- added either for diagnostic, analytical, or therapeutic applications into the interior of the microdialysis chamber 32. In accordance with a preferred --ir L of this invention the entry and exit tubes 28 and 30, respectively, are made of polyamide, fused silica, or other materials consistent with the objectives of resistance to high internal and/or external pL~iULe~ small size, and biological inertness. Each tube is of sufricient length to reach outside of the tissue entry port. The inlet tube is preferably Woss/32746 2 1 9 1 303 P~ 78l attached to a liquid pump (not shown). That pump may be a mechanically driven syringe pump and is coupled to the inlet tube 28 with a luer-lock fitting (not shown), with or without adapters, such as polyethylene tubing. This arrangement enables the pump to deliver the microdialysis medium to the bottom of the microdialysis probe.
As can be seen clearly in Fig. 2, the distal end 28A of the entry tube 28 and the distal 30A of exit tube 30 are situated preferably farthest from each other in order to allow a maximum circulation of the fluid within the chamber 32. This action allows maximum efficacy of the solute ~yr~h~n~e. The direction of flow of the fluid through the tubes and microdialysis chamber is shown by the arrows in Figs. 2 and 3.
Both the entry and exit tubes 2 8 and 3 0 respectively, are selected and designed such that they pass through the access port 12 . That port may be any suitable conv~nt; nn~ 1. such as is available from various manufacturers, e.g., Camino I,aboratories, Inc., for the purpose of inserting the primary invasive device (s) through a common entry site. The exit or outlet tube 30 serves as the means to collect the microdialysis medium from the probe's chamber 32 once the analytes of interest have diffused across the dialysis ~lle, and thus serves as an egress for the microdialysis medium from the probe. To that end, the exit tube 30 is of such a length as to remove the microdialysate outside the tissue to a point where it can be cnl 1 ect~d.
The primary purpose of the central tube's lumen 22 is to serve as a passage for the releasable J i n~ of a primary invasive device e.g., a probe 24, or any other device (not shown). The central lumen can also be used to receive a rigid stylet (not shown) in the event that no primary device is intended for use. The inner diameter of the lumen can be fabricated either to fit tightly li.e., press fit) or loosely - (i.e., slip-fit) the primary invasive device. When the lumen is sized to allow the slip-fitting of the primary devices therein, the depth of penetration of the microdialysis probe 20 and the primary probe or device 24 can be ~n~r~nd~ntly adjusted.
wossl32746 - 2 ~ 03 F~~ 5.~ 78l --In some instances the central tube 22 may replace the sheath that is uDed to protect the delicate cable or equivalent of the primary invasive device. In these circumstances, the cable of the primary invasive device would be conci~lpred ~s primary invasive device.
~ he semi-p~- --hl e membrane serves the primary function of creatlng a fluid compartment within the fluid matrix of a tissue, such as brain, and allows only passive diffusion of small molecular weigh solutes across its pores. To that end the micro-dialysLs ~ e may be made from Le~ elc.ted cellulose and having a permeability limit such as 6000 Dalton. With this material molecules with ~ c~ r weight greater than 6000 Dalton will not pass therethrough, whereas molecules of less than 6000 Dalton will pass therethrough. Other materials besides e~el el~ted cellulose may be used, and other cut-offs different from 6000 Dalton may be used, to permit the dialysis of --leclllec of different ---lecl~l Ar species. However, it is imperative that the dialysis membrane used must be capable of withstanding ~L~DUL~S created by fluid flow within and ~Lesau-e exerted by the tissue environment, such as intracranial fluid. Regenerated cellulose membranes are used in the preferred ~ L since such materials will withstand ~ eSDULe:S up to 610 mm ~g, approximately three times higher than the highest intracranial ~:eDDUL~:: to be encountered.
The central tube 22 may be of any suitable length 80 that its top edge 48 (Fig. 2~ is located adjacent the entry port 12 through the skull. In accordance with a preferred -'i- : of the invention, the inlet and outlet tubes 28 and 30 extend along and are secured to the outer surface of the central tube 22 by se~uL~ means, e.g., an adhesive, (not shown). This arrA, - I_ ensures that the inlet and outlet tubes do not cause damage to adjacent tissue, as could occur if the probe 20 was extended through an arcuate path or track into the brain. In such a case, if the inlet and outlet tubes did not extend along the central tube they could take a different track through the brain than the central tube 22 thus ~i~r-gin~ adjacent tissue.
Wo 9S13274G 2 1 q ~ 3 0 3 PCT/US9S/06781 In Figs. 4 and 5 there is shown the distal end of the alternative ' - ' i L 100 of a microdialysis probe of thi6 invention. The probe 100 includes two microdialysis rh~ D to permit simultaneous perfusion of the two chambers under different conditions, e.g., flow rate, medium composition. ThuD, one dialysis function, e.g., a diagnostic $unction, can be carried out in one chamber, and a second dialysis function, e.g., a therapeutic function can be carried out in the other chamber at the same time.
The probe 100 ~ir~l ly comprises a dual walled tube 102 having an outer wall 104 and an inner wall 106. The tube 102 is preferably formed of the same material as that of the tube 22 of the probe 20 described heretofore. The inner wall 106 includes a central p~cF?, _y 108 extending throuqh it for receipt of the primary probe 2 4 .
As can be seen clearly in Fig. 5, four p~ccRs~ _yD 110, 112, 114, and 116 extend through the dual walled tube 102. Each of the r~Cca~J _y~ extends for approximately ninety degrees of the circumference of the dual walled tube. The p:~cs~, _YD 110 and 112 from the inlet and outlet, respectively, to a first microdialysis chamber 118, while the p~cca~ yD 114 and 116 from the inlet and outlet of the second microdialysis chamber 120.
The microdialysis rh: ~~ D 118 and 120 are each semi-annular in shape and are formed by a common cylindrical outer wall 122 of the same semi r ~ -hle material as the outer wall 34 of the probe 20. The cylindrical outer wall 122 extends 4...,.~C-.,I ically about the outer wall 104 of the dual walled tube 102, and is spaced slightly therefrom to define the two rh~ ' ~~ D 118 and 120 theLebe~ . The outer wall 122 is secured in place about its top peripheral edge 124 by a ring of glue 126 of the same compo6ition as that described heretofore. In a similar manner the bottom peripheral edge 128 of the s~ni,-- --hle - ' ~ e outer wall 122 is secured in place by a ring of glue 130, which is also of the same composition as that described heretofore.
The dual walled tube 102 includes a pair of longit~Ainllly extending ribs 132 and 134 (Fig. 5) projecting out of the outer surface of the dual walled tube 102. These ribs are located _ _ _ _ _ W09~327.~6 21 9 1 3()3 E~l/~8, ~C 781 --diametrically opposite each other, with rib 132 being located at the interface of pAI f~A5__ YD 110 and 114 and with rib 134 being located at the interface of passageways 112 and 116. The ribs are each of a height es,,ual to the distance separating the inner surface of the SC~1n;rP ~~hle outer wall 122 and the outer surface of the dual walled tube so that they divide the space between the outer wall 122 and the dual walled tube into the two semi-annular chambers 118 and 120.
The bottom of each of the p~sa, _YD 110, 112, 114 and 116 is sealed by a plug of glue 136 of the same type as described earlier . The top of each of the pA--a jeways terminates in a conduit. In particular, the inlet pA4~ a~J~IAAy 110 to microdialysis chamber 118 terminates in a conduit 138 while the outlet pA~Iag y 112 to that chamber terminates in a conduit 140. In a similar manner the p~C:sal,_ yD 114 and 116 to and from the other microdialysis chamber 120 terminate in respective conduits (not shown).
The pA~a, _y 110 ~ icateS with the bottom of the microdialysis chamber 118 via a plurality of holes or apertures 142, while the pAR~ y 112 1 ~Aates with the top of that microdialysis chamber via a plurality of holes or ~eL~u~-s 144.
Thus, a microdialysis medium may be pumped from a pump (not shown) cnnn~ct~ to the inlet conduit 110, ..l.aLe:U~UI- that medium will flow through the inlet conduit 138 into the ;cAting pA~Aa~_ _y 110 through the a~ LUL~I3 142 into the bottom of the microdialysis chamber 118, through that chamber out of the ap~LLuL~s 144 into the pA~as _y 112 and from there through the outlet conduit 140 in the direction of the arrows shown in Fig.
4. Another microdialysis medium may be pumped from another pump (not shown) into the inlet conduit cnnn~rtc~ to rAAa~ y 114 to the microdialysis chamber 120 in a similar manner. That medium will then pass out of the chamber 120 into the pas__, _y 116 and the i iA~ting outlet conduit.
As should be appreciated by those Dkilled in the art, the microdialysis probe 100, in addition to providing a pair of microdialysis chambers 118 and 120, also provides for the LLa~lD~UL L of the dialysis medium to and from those chambers via -W09~l32746 2 1 9 ~ 3~3 F~~ 81 internally located pAI ~ageways~ i.e., the pA~A~, _yb in the dual walled tube 102. That dual walled tube can be readily fabricated, e.g., ~xLLuded from any suitable material, e.g., polyester, polyamide or TEFLON~.
It should be pointed out at this juncture that a micro-dialysis probe can be c.,..DL.u~ Led to incoL~L,.~te more than the two microdialysis rh: ' ~Q shown in the ~ L 100.
As should now be appreciated by those skilled in the art, the probes 20 and 100 of this invention provides an additional capability, namely, microdialysis, to the capability of the primary device with minimal increase in diameter over that of the primary device. Further still the probes 20 and 100 do not require an inr~ c, L access port other than port 12, or make a separate track or laceration through the tissue being sampled, analyzed or treated. Thus, the subject invention eliminates most, if not all, of the problems the prior art set ~orth above and offers much greater adaptability in order to be suitable for several possible applications.
In accordance with one preferred : - ' i - - of this invention, the microdialysis probes 20 and 100 are sufficiently small, e.g., have an external diameter of 4 mm and a length of at least 30 mm, to enable each to be a~ Led within a conv~-ntirmAl skull access port, giving a surface area of 377 sS~uare mill~r t~r-:. This area is approYimately 100 to 300 times greater than the prior art dialysis prob{~s. Accordingly, microdialysis probes c-...DLLu~;Led in ~ccc,Ldal.c2 with this invention can provide a flow rate approaching 100 ul/minute without sacrificing ef~iciency or adversely depleting interstitial space of rhPm~CAl~ needed for r~nt~in;n~ tissue viability .
Some ~ lAry advantages of such a c~nfig~ration are: In a situation where only partial sampling of interstitial rhQmic~l~
is desired and larger dQpletion of these ~ ;CA1~ is unde6irable, one can use ~XLL~ -ly low flow rates (1-4 ul/min) achieving 80-10096 efficacy. The illL e~Ded surface area of the probes 20 and 100 also translate into a r~ lr-tinn in variability, over time and from patient to patient, because of the greater _ _ _ _ _ _ _ _ _ _ _ wo 95/32746 2 1 9 1 3 0 3 r~ 7 e 1~781 amount of tissue which is sampled. In a situation where a fast depletion of endogenous toxins is desired, a very high flow rate can be used ~y properly nhnnc;ng the ~nnfi~lration. For example, the probes 20 or 100 may be used to remove water, in the case of edema, by dialyzing a hypertonic Dextran solution Or a ~ clllAr weight of 100,000 Dalton, or to remove ammonia, in the case of acute liver failure. In these therapeutic applications, it is pos~;ihle to Du~eLruse at significantly higher flow rates, e.g., 1 ml/min or higher. This means that greater amounts of toxic substances can be removed from the tisque when the patient's vasculature is unable to do so, e . g ., becau8e of pathnl o~; n2l 1 1 y high intracranial pL~ ULe which pinches shut the venous outflow, or because of pathologically high levels of ammonia in the blood.
In a setting where a rh2~rr-retltical agent is to be dialyzed out, a greater surface area can be exposed at low, medium or high flow rate, rlc-p~n~inq on whether or not a simultaneous sampling of its erfects on interstitial chemistry is desired. The cl, - l ation of the infused drug can be easily adjusted and adapted according to f low rate to get the maximum therapeutic advantage. All of these advantages are obtained ~rom a larger _ize dialysis probe, without any significant i~crease in the amount of tissue damage over the size of the primary probe.
The primary probe, with which the microdialy6is probes 20 and 100 of this invention can be used, can comprise any conventional device, such as an intracranial ~e6auL~ probe, an eleo~Lu~llyDiological recording electrode, standardized 1- ,2 R~F'hl~
surgical ir~-L~ (e.g., a spinal needle, ~uch as a luer-lock syringe tip or cannula, usually having a beveled and sharp tip), etc. ~I'L~UV~L~ it is poss2hle to easily adapt the microdialysis probe described here to multiple types of primary probes, the ~1-'2 2 t~r of the primary probe being the only parameter of significance to change, from the p_~Dl.e-;~ive of the microdialysis probe. In cases where no primary probe is intended for use, a li~LU~;LU ~, such as a stylet or a beveled cannula, may be selected based purely on cnnR~2~C~rations for delivery (cutting or blunt, flexible or rigid, plâstic or steel), and can be obtained W0 95l32746 2 1 9 1 3 0 3 ~ 78l ec ; r;~l 1 y and readily, to be u8ed as the primary probe for delivery purposes.
As should be appreciated from the foregoing the subject invention provides a microdialysis probe which can use, either simult~neo~lcl y or i ntlDrDrl~Dntly~ the same entry and passage as that used by other invasive devices; thus m;nimi ~:in~ or eliminating an increased possibility of infection due to use of the microdialysis probe, and minimizing or eliminating increased tissue damage caused by the physical insertion of the probe is described. Thus, the subject invention provides the clinician or scientific researcher with a means of performing microdialysis via a single entry passage in the body along with u6e of one or more other invasive device6. This aLL~ 1 of microdialysis probe with other invasive devices offers maximal flexibility in logistic terms , i . e ., the potential to stock primary probes separately from microdialysis probes and use the combined configuration at the phy6ician'6 option; and to adjust the depth of the two probes in~DpDn~Dntly. Most importantly, it offers methods for sampling and theri~re~ltirAlly modifying the rhDmi~
environment of tissue with minimal invasiveness.
Without further elaboration, the foregoing will so fully illustrate our invention that others may, be applying current or future knowledge, adopt the 6ame for use under various conditions of service.
Claims (30)
1. A microdialysis probe (20, 100) arranged to have a primary probe (24) releasably secured to it to enable the microdialysis probe and the primary probe to be extended as a unit through a common opening into the body (10) of a living being, characterized in that the microdialysis probe (20, 100) can be used for selective sampling and/or administration of dialyzable compounds in biological fluids from living tissue within the body (10) of the being and the primary probe (24) can be used for some other function within the body of the being, said microdialysis probe comprising means (22, 106) for releasably mounting said primary probe (24) to said microdialy-sis probe, a dialysis chamber (26, 118, 120) having a wall (34, 122) formed of a semi-permeable material having a pore size larger than the molecular weight of the dialyzable compounds, an inlet passageway (28, 138) to said chamber (26, 118, 120) and an outlet passageway (30, 140) from said chamber.
2. The microdialysis probe of Claim 1 characterized in that said dialysis chamber is elongated and has a longitudinal axis (36), a distal end portion (38, 128) and a proximal end portion (40, 124), and wherein said means for mounting said primary probe comprises a lumen (22, 106) having a longitudinal axis extending parallel to the axis of said chamber, said lumen being sized to accommodate said primary probe therein.
3. The microdialysis probe of Claim 2 characterized in that said dialysis chamber is of annular shape and has an inner cylindrical wall (48, 104), and wherein said wall of said semi-permeable material comprises an outer wall of said annular shaped dialysis chamber, said inner wall defining said lumen therein.
4. The microdialysis probe of Claim 3 characterized in that the inner wall extends through at least the entire length of said outer wall of said annular microdialysis chamber.
5. The microdialysis probe of Claim 3 characterized in that said inner wall of said chamber has a proximal end portion and wherein said outer wall of said chamber has a proximal end portion, with said proximal end portion of said inner wall extending in the proximal direction substantially beyond the proximal end portion of said outer wall.
6. The microdialysis probe of Claim 5 characterized in that said inlet passageway and said outlet passageway each include a distal portion located within said chamber and proximal portion located outside said chamber, said proximal portions of said passageways extending parallel to the longitudinal axis of said inner wall along said proximal portion of said inner wall (22, 104).
7. The microdialysis probe of Claim 2 characterized in that said inlet passageway is an elongated tubular member having a distal end inclulding an opening and a proximal end including an opening, said distal end opening of said inlet passageway being located within said distal portion of said dialysis chamber, said proximal end opening of said inlet passageway being located outside of said dialysis chamber substantially beyond its proximal end portion.
8. The microdialysis probe of Claim 2 characterized in that said outlet passageway is an elongated tubular member having a distal end including an opening and a proximal end including an opening, said distal end opening of said outlet passageway being located within said proximal portion of said dialysis chamber, said proximal end opening of said outlet passageway being located outside of said dialysis chamber substantially beyond its proximal end portion.
9. The microdialysis probe of Claim 7 characterized in that said outlet passageway is an elongated tubular member having a distal end including an opening and a proximal end including an opening, said distal end opening of said outlet passageway being located within said proximal portion of said dialysis chamber, said proximal end opening of said outlet passageway being located outside of said dialysis chamber substantially beyond its proximal end portion.
10. The microdialysis probe of Claim 9 characterized in that said distal opening of said inlet passageway is located in a diametrically opposed side of said dialysis chamber from said distal opening of said outlet passageway.
11. The microdialysis probe of Claim 1 characterized in said probe comprises a pair of dialysis chambers (118, 120), and wherein each of said chambers has a wall (122) formed of a semi-permeable material, and respective inlet (138) and outlet passageways (140) coupled to the associated chamber.
12. The microdialysis probe of Claim 11 characterized in that each of said dialysis chambers is elongated and of semi-annular shape having a longitudinal axis, a distal end portion and a proximal end portion, and wherein said means for mounting said primary probe comprises a common lumen (106) having a longitudinal axis extending parallel to axes of said semi-annular chambers, said common lumen being sized to accommodate said primary probe therein.
13. The microdialysis probe of Claim 12 characterized in said wall (122) of said semi-permeable material makes up the outer walls of both of said semi-annular chambers, said common lumen (106) defining a common inner wall for each of said semi-annular chambers.
14. The microdialysis probe of Claim 13 characterized in that the inner wall extends through at least the entire length of said outer wall of said semi-annular chamber.
15. The microdialysis probe of Claim 13 characterized in that said inner wall has a proximal end portion and wherein said outer wall has a proximal end portion, with said proximal end portion of said inner wall extending in the proximal direction substantially beyond the proximal end portion of said outer wall.
16. The microdialysis probe of Claim 15 characterized in that the inlet passageway (138) and the outlet passageway (140) to one of said semi-annular chambers (118, 120) each include a distal portion located within said one semi-annular chamber and proximal portion located outside said one semi-annular chamber, with said proximal portions of said passageways extending parallel to the longitudinal axis of said inner wall along said proximal portion of said inner wall, and wherein the inlet passageway and the outlet passageway to the other of said semi-annular chambers each include a distal portion located within said other semi-annular chamber and proximal portion located outside said semi-annular chamber, with said proximal portions of said passageways extending parallel to the longitudinal axis of said inner wall along said proximal portion of said inner wall.
17. The microdialysis probe of Claim 12 characterized in that each of said inlet passageways is an elongated tubular member having a distal end including an opening and a proximal end including an opening, said distal end opening of one of said inlet passageways being located within the distal portion of one semi-annular chamber, said proximal end opening of said one inlet passageway being located outside of said one semi-annular chamber substantially beyond the proximal end portion of said one semi-annular chamber, said distal end opening of the other of said inlet passageways being located within the distal portion of the other semi-annular chamber, said proximal end opening of said other inlet passageway being located outside of said other semi-annular chamber substantially beyond the proximal end portion of said other semi-annular chamber.
18. The microdialysis probe of Claim 12 characterized in that each of said outlet passageways is an elongated tubular member having a distal end including an opening and a proximal end including an opening, said distal end opening of one of said outlet passageways being located within the proximal portion of one semi-annular chamber, said proximal end opening of said one outlet passageway being located outside of said one semi-annular chamber substantially beyond the proximal end portion of said one semi-annular chamber, said distal end opening of the other of said outlet passageways being located within the proximal portion of the other semi-annular chamber, said proximal end opening of said other outlet passageway being located outside of said other semi-annular chamber substantially beyond the proximal end portion of said other semi-annular chamber.
19. The microdialysis probe of Claim 17 characterized in that each of said outlet passageways is an elongated tubular member having a distal end including an opening and a proximal end including an opening, said distal end opening of one of said outlet passageways being located within the proximal portion of one semi-annular chamber, said proximal end opening of said one outlet passageway being located outside of said one semi-annular chamber substantially beyond the proximal end portion of said one semi-annular chamber, said distal end opening of the other of said outlet passageways being located within the proximal portion of the other semi-annular chamber, said proximal end opening of said other outlet passageway being located outside of said other semi-annular chamber substantially beyond the proximal end portion of said other semi-annular chamber.
20. A combination microdialysis probe (20, 100) and a primary probe (24) arranged to be extended as a unit through a common opening into the body (10) of a living being, characterized in that the microdialysis probe (20, 100) can be used for selective sampling and/or administration of dialyzable compounds in biological fluids from living tissue within the body of the being and the primary probe (24) can be used for some other function within the body of the being, said combination comprising a primary probe (24) and a microdialysis probe 20 comprising a central lumen (22, 106) for mounting said primary probe (24) therein so that said primary probe extends through said microdialysis probe and with said microdialysis probe extending generally concentrically about said primary probe, said dialysis probe additionally comprising a dialysis chamber (26, 118, 120) having an outer wall (34, 122) formed of a semi-permeable material having a pore size larger than the molecular weight of the dialyzable compounds, an inner wall through which said lumen extends, an inlet passageway (28, 138) to said chamber and an outlet passageway (30, 140) from said chamber.
21. The microdialysis probe of Claim 20 characterized in that said outer wall is cylindrical and said inner wall is cylindrical, whereupon said dialysis chamber is of annular shape.
22. The microdialysis probe of Claim 20 characterized in that the inner wall extends through at least the entire length of said outer wall of said annular miorodialysis chamber.
23. The microdialysis probe of Claim 22 characterized in that said inner wall of said chamber has a proximal end portion and wherein said outer wall of said chamber has a proximal end portion, with said proximal end portion of said inner wall extending in the proximal direction substantially beyond the proximal end portion of said outer wall.
24. The microdialysis probe of Claim 23 characterized in that said inlet passageway and said outlet passageway each include a distal portion located within said chamber and proximal portion located outside said chamber, said proximal portions of said passageways extending parallel to the longitudinal axis of said inner wall along said proximal portion of said inner wall.
25 . The microdialysis probe of Claim 24 characterized in that said distal opening of said outlet passageway is located within a proximal portion of said dialysis chamber, and wherein said distal opening of said inlet passageway is located within a distal portion of said dialysis chamber.
26. The microdialysis probe of Claim 25 characterized in that said distal opening of said inlet passageway is located in a diametrically opposed side of said dialysis chamber from said distal opening of said outlet passageway.
27. The microdialysis probe of Claim 20 characterized in that said probe comprises a pair of dialysis chambers (118, 120), and wherein each of said chambers has an arcuate outer wall (122) formed of a semi-permeable material, an arcuate inner wall (104), and respective inlet (128) and outlet passageways (130) coupled to the associated chamber, said arcuate inner walls of said pair of chambers being contiguous with each other and with said lumen extending therethrough.
28. The microdialysis probe of Claim 27 characterized in that each of said dialysis chambers elongated and of semi-annular shape having a longitudinal axis, a distal end portion and a proximal end portion.
29. The microdialysis probe of Claim 28 characterized in that said wall (122) of said semi-permeable material makes up the outer walls of both of said semi-annular chambers.
30. The microdialysis probe of Claim 29 characterized in that the inner wall extends through at least the entire length of said outer wall of said semi-annular chamber.
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| Application Number | Priority Date | Filing Date | Title |
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| US08/250,121 US5441481A (en) | 1994-05-27 | 1994-05-27 | Microdialysis probes and methods of use |
| US08/250,121 | 1994-05-27 |
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| CA2191303A1 true CA2191303A1 (en) | 1995-12-07 |
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| CA002191303A Abandoned CA2191303A1 (en) | 1994-05-27 | 1995-05-26 | Microdialysis probes and methods of use |
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| US (1) | US5441481A (en) |
| AU (1) | AU2654995A (en) |
| CA (1) | CA2191303A1 (en) |
| WO (1) | WO1995032746A1 (en) |
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| US20220080101A1 (en) * | 2020-09-15 | 2022-03-17 | Hilltop BioSciences, Inc. | System and method for aseptic collection of mammalian amniotic fluid |
| CN112603386B (en) * | 2021-01-27 | 2022-05-06 | 河南省人民医院 | Brain tumor operation cavity interstitial fluid sampling monitoring diagnosis and treatment device |
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| US2936761A (en) * | 1958-04-25 | 1960-05-17 | Snyder Henry Howard | Catheter |
| US3995623A (en) * | 1974-12-23 | 1976-12-07 | American Hospital Supply Corporation | Multipurpose flow-directed catheter |
| US4072146A (en) * | 1976-09-08 | 1978-02-07 | Howes Randolph M | Venous catheter device |
| DE2734248A1 (en) * | 1977-07-29 | 1979-02-08 | Fresenius Chem Pharm Ind | PORTABLE ARTIFICIAL KIDNEY |
| US4274417A (en) * | 1978-09-22 | 1981-06-23 | National Research Development Corporation | Instruments for use in the measurement of gases in body fluids |
| US4437856A (en) * | 1981-02-09 | 1984-03-20 | Alberto Valli | Peritoneal catheter device for dialysis |
| US4406656A (en) * | 1981-06-01 | 1983-09-27 | Brack Gillium Hattler | Venous catheter having collapsible multi-lumens |
| US4516580A (en) * | 1981-12-28 | 1985-05-14 | Polanyi Michael L | Continuous blood gas monitoring |
| SE434214B (en) * | 1982-12-01 | 1984-07-16 | Carl Urban Ungerstedt | DIALYSIS PROBLEM, INTENDED FOR INFORMATION IN BIOLOGICAL Tissues |
| US4623329A (en) * | 1983-12-15 | 1986-11-18 | The Procter & Gamble Company | Drainage and infusion catheters having a capillary sleeve forming a reservoir for a fluid antimicrobial agent |
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| US5207640A (en) * | 1991-03-27 | 1993-05-04 | Hattler Brack G | Method of anesthetizing a patient |
| US5191900A (en) * | 1991-04-10 | 1993-03-09 | The Board Of Trustees Of The University Of Illinois | Dialysis probe |
| DE4130742A1 (en) * | 1991-09-16 | 1993-03-18 | Inst Diabetestechnologie Gemei | METHOD AND ARRANGEMENT FOR DETERMINING THE CONCENTRATION OF INGREDIENTS IN BODY LIQUIDS |
| US5212527A (en) * | 1992-04-20 | 1993-05-18 | Xerox Corporation | Dual mode oil applying blade for applying different oil rates depending on operating mode of an image creation apparatus |
| US5254084A (en) * | 1993-03-26 | 1993-10-19 | Geary Gregory L | Peritoneal catheter device for dialysis |
-
1994
- 1994-05-27 US US08/250,121 patent/US5441481A/en not_active Expired - Fee Related
-
1995
- 1995-05-26 WO PCT/US1995/006781 patent/WO1995032746A1/en active Application Filing
- 1995-05-26 AU AU26549/95A patent/AU2654995A/en not_active Abandoned
- 1995-05-26 CA CA002191303A patent/CA2191303A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US5441481A (en) | 1995-08-15 |
| AU2654995A (en) | 1995-12-21 |
| WO1995032746A1 (en) | 1995-12-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |