Patent Abstract:
this present invention provides real - time in vivo sampling via ultra - small volume microdialysis of the intervertebral disc to assay single molecules of interest . the invention consists of three lumena , two that are capped with a membrane capable of sampling tissues via diffusion . a guide wire can provided between these two lumena so that they may be extended beyond the housing of the three lumena and directed via the guide wire . the third lumen can be utilized for injection or aspiration . theoretically , agents including treatments such as stem cells or pharmaceutical agents may be introduced to the disc via this third lumen and the real - time effects may be assayed with the first two lumena . the three lumena may be placed adjacent to each other or in a concentric fashion to minimize the total size of the device .

Detailed Description:
in describing the preferred embodiments of the present invention illustrated in the drawing , specific terminology is resorted to for the sake of clarity . however , the present invention is not intended to be limited to the specific terms so selected , and it is to be understood that each specific term includes all technical equivalents that operate in a similar manner to accomplish a similar purpose . fig1 and 2 show a microdialysis sampling and delivery device 100 in accordance with an embodiment of the invention . the device 100 is intended for insertion into biological tissues , such as intradiscal placement which comprises a series of lumina and membranes . the device generally includes a membrane 3 , outer wall 4 , inner wall 20 , inflow lumen 5 . outflow lumen 6 , injection / aspiration lumen 7 , guide wire 8 , injection port 11 and opening 12 . the device has an external fixed shell , i . e . outer wall 4 . the outer wall 4 can be rigid , or semi - rigid and is constructed of metal , plastics or other materials to provide protection for the analytical device . the outer wall 4 can have a circular cross - section , so that the device 100 is generally an elongated tubular shape . it will be appreciated that any suitable material can be utilized having different strength , rigidity and pliability . the outer wall 4 defines an enclosure having an inner space that contains at least three lumina : an inflow lumen 5 , an outflow lumen 6 , and an injection / aspiration lumen 7 . the inflow and outflow lumen 5 , 6 are contained within the inner wall 20 ( which is contained within the outer wall 4 ) or may be separate ( as shown ), and at least a portion of the inner wall 20 can be directly in contact with a portion of the outer wall 4 . the inner wall 20 can have a similar cross - sectional shape as the outer wall 4 such as a circle to form a circular tube . or , the inner wall 20 can have a different cross - sectional shape such as a rectangle with a top inner wall , bottom inner wall and two opposing inner side walls ( as shown in fig2 ). an internal dividing wall 22 is provided between the inflow and outflow lumina 5 , 6 , within the inner wall 20 . the internal dividing wall 22 optionally contains a guide wire 8 . the two lumina 5 , 6 are thereby configured to carry a dialysate mixture . preferably , those inflow and outflow lumina 5 , 6 are adjacent one another , as shown . the lumina 5 , 6 are separated from each other by the internal wall 22 and / or the guide wire 8 or other barrier so that fluid cannot move between the lumina 5 , 6 except around the distal end of the guide wire 8 . that is , the dividing wall 22 is impermeable so that the liquid or material in the lumina 5 , 6 cannot pass through the dividing wall 22 . the dividing wall 22 is shown in fig2 as being two separate walls that extend vertically within the inner walls . however , the dividing wall can be a single wall that is either a thicker wall to allow for the guide wire 8 or a thinner wall with the guide wire 8 located elsewhere within the device 100 . in addition , the dividing wall ( s ) 22 can be positioned horizontally or at another position within the inner walls 20 . the dividing wall ( s ) 22 are further show being linear and separating the interior space within the inner walls 20 in half so that the inflow lumen 5 is about the same size as the outflow lumen 6 . however , the dividing wall 22 can be configured to be non - linear and / or to separate the interior space so that one of the lumen 5 , 6 is larger than the other . still yet , the inflow lumen 5 and outflow lumen 6 need not be immediately adjacent to and touching one another ( and contained within or sharing at least a portion of the inner wall ( s ) 22 ), but can be entirely separate , each with one or more respective inner walls 22 . the inner wall 20 essentially forms an inner elongated container or tube that is located within the outer elongated container or tube defined by the outer wall 4 . the inner tube can move independent of the outer tube , so that , for instance , the inner tube can extend outward beyond the outer tube and be placed more precisely with respect to the target tissue 1 , 2 . thus , the inner tube can slide inward and outward with respect to the outer tube . in addition , the inner tube can be rotated within the outer tube or once deployed beyond the inner tube . the internal dividing wall 22 has a distal end that terminates just proximal to a microdialysis membrane 3 . in this manner and as shown by the arrows in fig1 , the fluid , gas other material ( preferably a dialysate mixture ) may flow in through the inflow lumen 5 , around the distal end of the guide wire 8 between the distal end of the guide wire 6 and the membrane 3 , and back in through the outflow lumen 6 . the cellulose ester microdialysis membrane 3 is semi - permeable and allows the transfer of substances of appropriate sizes (˜ 100 , 000 kdaltons ). the membrane 3 is fixed at the terminal ends of the inflow and outflow lumina 5 , 6 . the membrane 3 is affixed over the distal ends of the two lumina 5 , 6 at a distance of approximately 200 μm between the distal end of the internal dividing wall 22 and the membrane 3 . this creates a space 24 between the guide wire 8 and the membrane 3 through which material can pass from the inflow lumen 5 to the outflow lumen 6 . the membrane 3 is attached to a distal end surface of the inner wall ( s ) 20 of the middle lumina 5 , 6 . the membrane 3 can be cemented or glued in place to the inner wall ( s ) 20 . furthermore , an injection / aspiration lumen 7 is positioned adjacent to the inflow and outflow lumina 5 , 6 , and terminates at the end of the outer wall 4 . variations of this design include a device with the sampling unit retracted within the outer wall 4 or one with the sampling unit beyond the outer wall . furthermore , the sampling unit may be deployable and steerable ( via the guide wire ) to analyze structure or tissues adjacent to the fixed shell . typically the external fixed shell 4 is placed via a delivery device such as a needle . the external shell 4 and the accompanying lumina 5 , 6 , 7 can be of variable lengths likely 5 - 8 inches in length . the shell will likely be 25 - 27 gauge but may be variable . as illustrated in fig2 , the aspiration lumen 7 can be separate from the inflow and outflow lumen 5 , 6 , or can touch the inflow and outflow lumen yet would still consist of its own walls that would not be permeable to the other two lumena 5 , 6 . this device 100 can be delivered to target tissues 1 , 2 through a needle to protect its integrity . while the invention has been shown and described as having three lumina 5 , 6 , 7 , more lumen can be provided . preferably however , at least one lumen ( here shown as the injector / aspiration lumen 7 ) of a minimum of the three total lumen 5 , 6 , 7 is dedicated to delivery of substances into the target tissues 1 , 2 or aspiration of substances from the target tissue 1 , 2 . and , the injection lumen 7 can be provided within its own tube that includes another inner wall container . the injection tube can be positioned inside the outer wall 4 of the housing and outside of the inner tube of the inflow / outflow lumina 5 , 6 , as shown . in addition , while the guide wire 8 is shown between the two lumina 5 , 6 , it can be located along the outer wall 4 , or between the lumen 5 , 6 and the injection / aspiration lumen 7 . other suitable variations are also within the scope of the invention . for instance , though the inflow and outflow lumina 5 , 6 are shown in a side - by - side relationship , they can be in a concentric relationship , such as with the inflow lumen 5 at the center surrounded by the outflow lumen 6 , and with the injector lumen 7 to the side or concentric thereto . and , the inner wall 20 can have a circular or oval cross section . furthermore , the distal element of the microdialysis sampling unit 10 can either project beyond the outer wall 4 ( as shown ), or lay within the outer wall 4 . also the distal element may be housed with the supporting structure at placement but may be deployable and steerable in a circular fashion to a set distance via a steering mechanism such as a guide - wire 8 built into the wall 22 separating the dialysis lumina 5 , 6 . for instance , the wall 22 between the two sampling lumina can be reinforced and house a guide - wire mechanism 8 in a hollow structure . a dialysis pump 9 is provided to drive a solute through the inflow lumen 5 to sample and / or exchange substances from the target tissue at the site of the membrane . the solute will return through the outflow lumen 6 to the collection chamber 10 . thus , the pump 9 is in fluid communication with the inflow lumen 5 , and the collection unit 10 is in fluid communication with the outflow lumen 6 . the collection unit 10 can be , for instance , a well or a series of wells that collects the sample . in operation , the device 100 allows for the simultaneous sampling of biological substances . furthermore this may be done prior to and after injection in a real - time fashion . a dialysate mixture or solute is introduced into the inflow lumen 5 by the pump 9 . the solute flows to the distal end of the inflow lumen 5 , where the ph difference between the solute and the target tissue 1 , 2 across the membrane derives the diffusion . at the same time , a medication or biologic agent ( or other substance to be studied ) may be introduced to the target tissue 1 , 2 through the injector lumen 7 . the tissue 1 , 2 reacts to the medication or biologic agent , and the biological substances that would react to that injectate would be sampled across the membrane 3 . the membrane 3 works by simple diffusion , whereby a gradient across the membrane ( i . e ., ph of solute different than ph of intradiscal space ) allows the diffusion of biological substance across it to be sampled . this gives relative levels of these biological substances within the disc via real - time in vivo sampling . the membrane 3 does not allow the dialysate or solution to cross into the ivd ( so that the dialysate or solution stays in the lumena 5 , 6 , and only the gradient allows the molecules of interest to cross over . biological substances that are problematic might also be removed . that mixture is then collected through the outflow lumen 6 , and deposited in the collection unit 10 . thus , the device 100 allows substances beyond the membrane 3 to be sampled . the dialysis pump 9 moves the fluid at a predetermined rate sufficient to move the fluid from the inflow lumena 5 past the membrane 3 into the outflow lumena 6 and into the collection reservoir 10 . however , the rate is sufficiently slow to allow appropriate diffusion . the membrane 3 is only over lumina 5 , 6 because that is the entirety of the sampling unit . the membrane 3 is not placed over the injector lumen 7 because it is needed for injection or possibly aspiration . a syringe is attached to the injection port 11 possibly via a connector tube to inject or aspirate samples . it should be noted that although the arrows in fig1 show movement both in and out of the injection / aspiration lumen 7 , only one movement occurs at a given time . that is , a substance can be injected into the lumen 7 , which moves toward the target tissue 1 , 2 ( right to left in the embodiment shown ). or , substance can be aspirated out of the lumen , which moves away from the target tissue 1 , 2 ( left to right in the embodiment of fig1 ). the pump 9 preferably provides a slow flow rate of about 1 microliter to 1 milliliter per minute . the desired flow rate can vary depending on the sensitivity of the assay . the invention is able to perform micro - dialysis with a very small volume of sample , under 1 milliliter and as little as 1 microliter . of course , any suitable flow rate and sampling volume can be provided . the present invention is able to elucidate the role of various cytokines and neuropeptides within the degenerative cascade of the intervertebral disc . the device 100 can obtain samples at individual molecule using the membrane 3 . the invention is able to obtain samples of the target tissue 1 , 2 in vivo and determine , for instance , how the ivd changes when a biological agent injected . thus , in vivo changes in the ivd neurotransmitters can be analyzed before and after a biological agent is administered to the target tissue 1 , 2 . the device 100 samples tissue locations such as the intradiscal milieu in a real - time fashion . biological tissues contain various cytokines , neuropeptides and substances engaged in the transport of signals in a catabolic or anabolic state . in order to understand the functioning in structures such as the intervertebral disc , which as this time we only understand from cadaveric and surgical specimens , elucidating the real - 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65 . the description and drawings of the present invention provided in the paper should be considered as illustrative only of the principles of the invention . the invention may be configured in a variety of ways and is not intended to be limited by the preferred embodiment . numerous applications of the invention will readily occur to those skilled in the art . therefore , it is not desired to limit the invention to the specific examples disclosed or the exact construction and operation shown and described . rather , all suitable modifications and equivalents may be resorted to , falling within the scope of the invention .