Percutaneous serial sampling port for biologic investigations and therapies

Abstract

A device, system, and method are provided for accessing and sampling target tissues in body cavities. In some embodiments, the device includes a sheath with a sampling lumen for needle passage, a distal flange for anchoring, and optional features like balloons, cuffs, and suction catheters. The system may incorporate a sampling needle, possibly with an SPME coating. Insertion methods use guidewire and dilator techniques for minimally invasive placement. This enables repeated, low-risk sampling for diagnostic and research applications.

Description

PERCUTANEOUS SERIAL SAMPLING PORT FOR BIOLOGIC INVESTIGATIONS AND THERAPIESCross-Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 675,838, filed on July 26, 2024, now pending, the entire contents of which are incorporated herein by reference.Field of the Disclosure

[0002] The present disclosure relates to devices and methods for allowing the introduction of fine gauge measurement devices (such as needles) into tissues, and in particular, into tissues within body cavities, and for obtaining multiple percutaneous biologic samples using solid phase microextraction or other sampling method.Background of the Disclosure

[0003] It is possible to obtain samples of drugs or natural biologic substances using extremely efficient and minimally invasive methods such as Solid Phase Microextraction (SPME). In SPME. a thin needle (such as an acupuncture needle), or “fiber,” coated with an absorptive layer can be placed into almost any normal or abnormal (e.g., cancer) biologic tissue with little risk for trauma or significant bleeding. Thus, relatively easy, repetitive organ measurements of important naturally occurring biologic molecules or administered drugs is now possible. This is an important advance because it allows faster confirmation of biologic responses or drug deliveries without requiring indirect methods like radiologic tests or other surrogate measurements. Unfortunately, such thin needles can bend easily and miss their targets because of veering off course or uncertainties in depths of penetrations. Furthermore, samples are often desired of organs in deep body cavities requiring the coated needles to interact with or be obstructed by intervening tissues that could contaminate measurements.Brief Summary of the Disclosure

[0004] The present disclosure addresses the aforementioned needs by providing a device, system, and method for accessing and sampling target tissues of an individual. In some embodiments, the disclosure includes a sheath with a proximal end, a distal end having a flange, and a sampling lumen configured for passage of a sampling needle. Optional features include asampling head with ports, suction catheters, inflatable balloons for flange formation or fixation, tissue ingrowth cuffs, and additional lumens for fluid sampling.

[0005] In some embodiments, a method for inserting the sheath involves a modified guidewire technique with dilator assistance, optionally through a surgical access port. The system may include the sampling needle. Such a sampling needle may include an absorptive coating for SPME.

[0006] Alternative embodiments integrate the sampling head into the proximal end and provide various fixation mechanisms at the distal end. The various embodiments and optionally with fixation features enable minimally invasive, repeated sampling with reduced risk.Description of the Drawings

[0007] For a fuller understanding of the nature and objects of the disclosure, reference should be made to the following detailed description taken in conjunction with the accompanying drawings.

[0008] Figure 1 A: A side elevation view of a device according to an embodiment of the present disclosure.

[0009] Figure IB: A perspective view of the device of Figure 1A.

[0010] Figure 1C: A top view of the device of Figures 1 A and IB.

[0011] Figure 2: Another embodiment of a device according to the present disclosure and including a suction port.

[0012] Figure 3: A detail view of a balloon on a catheter tip according to another embodiment of the present disclosure.

[0013] Figure 4: A detail view of a flange on a catheter tip according to another embodiment of the present disclosure.

[0014] Figure 5: A side elevation view of a device according to another embodiment of the present disclosure.

[0015] Figure 6A: Photograph of an example SPME needle.

[0016] Figure 6B: Photograph of another embodiment of an example SPME needle.

[0017] Figure 7: Front view (left) and lateral cross section view (right) of thorax of an individual.

[0018] Figure 8: Front view (left) and lateral cross section view (right) of thorax of an individual. Needle in

[0019] Figure 9: Front view (left) and lateral cross section view (right) of thorax of an individual. Wire in

[0020] Figure 10: Front view (left) and lateral cross section view (right) of thorax of an individual. Dilator in

[0021] Figure 11: Front view (left) and lateral cross section view (right) of thorax of an individual. Back load

[0022] Figure 12: Front view (left) and lateral cross section view (right) of thorax of an individual. In place, no cap

[0023] Figure 13: Front view (left) and lateral cross section view (right) of thorax of an individual. Cap on

[0024] Figure 14: Lung collapsed

[0025] Figure 15: Lung inflated

[0026] Figure 16: Vacuum applied. Biopsy needle in place; Different depthsDetailed Description of the Disclosure

[0027] To overcome these barriers, the present disclosure provides a fine needle delivery system (FNDS) which can be positioned in precise desired locations by using imaging guidance or surgical placement. The FNDS may include stabilization features that allow for high reliability sampling penetrations into target tissues. The FNDS can be used in various body sites including the abdominal canty and, with an adaption, use in the thoracic cavity as well. It provides for the introduction of multiple fine needles (or other sensors of having sufficiently thin dimensions) through a port to prescribed depths. It can be maintained as an indwelling devicetraversing the skin with durations (generally weeks) possible for indwelling catheters and can be removed simply without requiring anesthesia. Some embodiments of the presently disclosed device allow even longer-term placement (months) with removal using local anesthesia. The present disclosure is important because researchers working with live animals will be able to do experiments more efficiently by reducing animal numbers and operations needed to obtain tissues. Also, similar to the convenience and improved safety of indwelling intravenous ports (such as for antibiotics or chemotherapies), humans will be able to have a port placed to measure direct effects on the pathologic tissues by regionally or systemically administered therapies to more quickly determine favorable or unfavorable responses.

[0028] Although described w ith reference to SPME. embodiments of the present disclosure are not limited to SPME technology. Other technologies that could be used include, but are not limited to, micro dialysis catheters, small-bore transducers (e.g., Millar catheters, ultrasonic cry stals, etc.), small diagnostic and therapeutic catheters (e.g., photodynamic sensing and / or delivery probes, etc.) SPME devices are sometimes referred to as fibers due to the small gauge of the needle (generally a solid needle, rather than hollow).

[0029] In an aspect, such as that depicted in Figures 1A-1C, the present disclosure may be embodied as a device 100 to provide access for sampling a target tissue of an individual. The device 100 includes a sheath 110 having a proximal end 112 with a sampling head 120, a distal end 114 configured to be fixed to a tissue, and a sampling lumen 116 extending between the distal end 114 and the proximal end 112. The sampling lumen is configured for passage of a sampling needle via the sampling head at the proximal end and through the distal end.

[0030] The sampling head 120 includes one or more sampling ports 122. Such sampling ports provide access to the sampling lumen such that sampling needle or other instruments may be passed through the sampling lumen by way of one of the one or more sampling ports. The sampling head 220 may include a vacuum port 224 (see device 200 of Figure 2). In this way. a vacuum (i.e., negative pressure) may be applied by way of the vacuum port using, for example, a suction catheter or the like. The sampling ports of the sampling head are generally sufficiently small in diameter such that a vacuum applied at the vacuum port is effective at the distal end of the sheath (e.g.. without the need to cap the sampling ports). In some embodiments, caps 230 are placed on one or more of the sampling ports to aid in maintaining a desired level of vacuum.

[0031] The distal end of the sheath may be configured to be fixed to a tissue by way of a balloon, flange, cuff, suture, or the like. For example, the sheath may include a cuff 134 at a location along a length of the sheath 110, which may permit surrounding tissue to grow into the cuff 134 so as to affix the sheath 110 end to the tissue. In another example, the sheath 310 may include an inflation lumen such that a balloon 332 may be selectively inflated or deflated at the distal end (see Figure 3). In another embodiment, the distal end of the sheath 410 may include a flange 436 (see Figure 4). The flange may itself prevent removal of the sheath from its position in the tissue. In some embodiments, the flange may be sutured to the tissue so as to fix the location of the sheath. Other techniques are known for affixing a sheath in position and are within the scope of the present disclosure. Embodiments may include more than one of these and / or other features.

[0032] The sheath may have a length which varies according to the need (i.e., according to the location in the body which needs to be accessed and the location of the sampling head external to the body). The sheath may be configured as described above. For example, the sampling lumen of the sheath may have a diameter of between 1 F and 5 F. inclusive.

[0033] In another aspect, the present disclosure may be embodied as a system for accessing a target tissue of an individual, the system having a sampling needle and a sheath. The sheath has a proximal end with a sampling head, a distal end configured to be fixed to a tissue, and a sampling lumen extending between the distal end and the proximal end. The sampling lumen is configured for passage of the sampling needle via the sampling head at the proximal end and through the distal end. The various components of the system (sheath, sampling head, sampling needle, etc.) may have any of the configurations as described above.

[0034] With reference to Figure 5, in some embodiments, the present disclosure may be embodied as a device 500 to provide access for sampling a target tissue of an individual. The device 500 includes a sheath 520 having a proximal end 522 and a distal end 524. The distal end 524 may include a flange 530. A sampling lumen 526 extends through the sheath 520 between the proximal end 522 and the distal end 524. The sampling lumen is configured for passage of a sampling needle, such as an SPME needle, from the proximal end, through the sheath, and through the flange of the distal end. For example, in various embodiments, the sampling lumen may have a diameter of 1-2 French (F). in some embodiments the sampling lumen may have a diameter of between 1 F and 5 F, inclusive.

[0035] In some embodiments, a sampling head 540 is configured to be attached to the proximal end 522 of the sheath 520. The sampling head 540 has one or more ports 542 providing access to the sampling lumen. In this way. a sampling needle may be inserted through a port of the sampling head and through the sampling lumen to obtain access to the target tissue.

[0036] In some embodiments, the device 500 further includes a suction catheter 550 which is configured for application of a vacuum to the flange 530 of the sheath 520.

[0037] An embodiment of the present device may be made using, for example, a modified vascular access sheath 2-8 French introduced into or proximate to the desired target tissue using any accepted surgical or interventional approach such as the Seidinger method. While there are several useful alternate embodiments, a short-term intrathoracic device will be described primarily, and then alternate embodiments will be mentioned. The following are descriptions of non-limiting, example embodiments of devices for providing access for tissue sampling and methods for deploying such devices.Short-term duration (< 7 days) intrathoracic 2 needle sampling embodiment

[0038] While performing Video-Assisted Thoracoscopic Surgery (‘WATS”) (thoracoscopy) a surgeon determines a location over the desired portion of the lung for sampling by using optical guidance or some other accepted localization method. An 18-gauge (0.9 mm ID) needle is introduced through the chest wall externally to internally. Then the surgeon introduces a standard 0.035"’ (0.875mm) J-wire though the needle and removes the needle. Over the wire is placed (external to internal) a dilator for a 4 F (1.3mm ID) vascular access sheath. For typical vascular access, the dilator would then be removed (leaving the wire in place) and reinserted (external to internal) within the entire access sheath assembly into the desired vessel. Instead, the dilator sheath is left in place and the 0.035” wire inside the chest is brought out through an existing VATS access port such that the wire passing through the thorax (into, and then out from the thorax).

[0039] This allows loading of a modified sheath onto the end of the wire exiting from the VATS port. The sheath along with the integrated suction tubing is then pushed in a retrograde fashion into the chest with a pusher catheter to load onto the dilation sheath in reverse fashion to have the sheath exit the chest (internal to external). Then the wire and sheath are removed leaving a flange of the catheter pulled tightly up to the rib interspace which prevents it frombeing withdrawn and keeps an end of the flange generally perpendicular to the lung surface — advantageous for later needle insertion. The suction tubing travels laterally from the insertion site and exits from the same VATS port it was introduced or can be moved to egress from another port if desired. The purpose of this suction line will be to stabilize the lung during biopsy as well as provide a tether for later extraction of the system. The 4F 15cm lung catheter is then trimmed to a length (4-8 cm) as determined by the thickness of the patient’s overlying chest wall tissues and the length of the SPME needle.

[0040] Then, a multiple access cap head is applied to the cut end (new proximal end) of the 4F catheter. Through this head multiple useful maneuvers can be performed including the introduction of #30 G (0.3 mm) SPME needles, which can be of different lengths to achieve different depths of sampling. In the illustration shown in Figure 14. 2 x 22G (0.6mm ID) catheter lumens are used. The depth of penetration can be confirmed by imaging or direct trial insertion observation through the thoracoscope. The lung is allowed to reinflate to enable the biopsy process later. When the biopsy is desired, suction is applied to the sheath (Figures 14-16).Because the acupuncture needle insertion lumens are so small, a majority of the applied suction is transmitted to the surface of the lung which temporarily fixates it. In embodiments w here a vascular access sheath is modified for use in the present disclosure, a diaphragm (normally present in such devices to prevent back bleeding) is removed to allow suction to be applied as described. Confirmation of contact with the lung occurs when suction flow rate falls quickly. This suction, combined with the 4F sheath preventing veering, forces the needle to penetrate the tissue surface to the desired depth. Furthermore, the suction confirms that no hemorrhage (unlikely with a 30 G needle) is occurring and reports bleeding if it does.

[0041] SPME needles typically remain in place for about 20 minutes and then are withdrawn. A hub of the needle prevents it from migrating into the sheath during this sampling. Finally, the ports are capped and the suction is turned off. Optionally, injection of vital dye into the assembly before turning off the suction would create a superficial mark on the lung to confirm the site of SPME. The assembly can be glued or sutured to the skin if desired to prevent dislodgement or migration beneath the skin’s surface. When no longer needed, the access cap(s) is (are) removed and the sampling sheath is retrieved from the VATS port using the suction tubing like removing a chest tube. This does not typically require sedation or anesthesia. If the device is to be used in the post-operative phase, the tubing could also exit a chest tube site.Short to Medium-term duration (0-8 weeks) body cavity site (thoracic, abdominal, cranial) multiple needle sampling embodiment

[0042] For these embodiments, the access sheath is introducing into the desired location by surgical technique or accepted imaging method. For instance, iodinated contrast, induced pneumothorax, induced pneumoperitoneum may be used to create a space to position the sampling assembly over the desired target organ using a Seidinger technique similar to placing other devices like vascular access catheters and chest tubes. Once in position, a functional flange may be created near the distal tip of the catheter to prevent dislodgement by inflating a distal tip balloon, expanding the semiflexible catheter material using a dilation balloon, activating a mechanical burr, or a similar method. If placed during laparoscopy or thoracoscopy, the tip flange can be anchored by temporary sutures to the target. Also, an inflammation inducing product could be applied to the region to speed integration and isolation of the flange into the targeted tissue. Depending on the application, integrated suction can be applied and used as described above. Care of the access port site would be similar to peripherally inserted central catheters (PICC) which provide medium term function. When no longer needed, the device may be extracted manually without the need for anesthesia.Short to Medium-term duration (0-8 weeks) soft-tissue multiple needle sampling embodiment

[0043] In some embodiments, such as those expected to remain in place for periods of up to 8 weeks, and where the tissue to be sampled is not within a body cavity, a tip of the device is configured to be inserted into a soft tissue of interest such as a muscle, organ likely to resist hemorrhage, or tumor. No suction, distal flange member, or additional tissue anchoring will be necessary other than for anchoring at the skin site like vascular catheters or other drains. The remainder of the system may remain the same as described above — e.g., with the ability to insert multiple devices into the target using the stabilizing effect of the sheath. Care and removal are as described above with respect to the short- to medium-term body cavity embodiment.Long-term duration body cavity and soft-tissue multiple needle sampling embodiment (0-6 months)

[0044] In some embodiments, such as. for example, those expected to remain in place for periods of time up to 6 months (or even longer), such long-term access will emulate the success of tunneled intrapleural catheters (e.g., Pleurx) for pleural effusions and peritoneal dialysiscatheters. The devices may be similar to the short- to medium-term body cavity embodiment described above but may be encased in silicone or other coating to enable long-term biocompatibility. Also, the shaft may have a cuff near the skin insertion site which allows for ingrowth of tissue preventing dislodgement and bacteria migration dow n the device tunnel. For example, the cuff may be a portion of a hook-and-loop fastener (e.g., the hook-side or the loopside of such a fastener) or other material known to allow' for ingrowth of tissue. In addition to the sampling channel, there may be an inflation lumen to inflate or deflate a distal flange balloon. Some embodiments may also include a cavity lumen to provide vacuum or sample fluid from the desired body cavity’. Care of such a long-term placement would be similar to tunneled silicone catheters including, for example, regular replacement of the sterile caps covering the access ports, covering the site with a membrane, etc. Removal of the device from the individual may require local anesthesia to free the cuff from the surrounding tissue to allow removal. An alternative embodiment is a totally implantable access port that would only domed silicone reservoirs for access w ith a Huber needle and a similar modification for introducing the SPME.Advantages and Improvements over existing methods.

[0045] Obtaining serial measurements from tissues of interest in biologic systems has generally required multiple invasive procedures necessitating sedation or anesthesia. The innovation of the present disclosure was conceptualized for use during the rapidly growing program of lung suffusion at Rosw ell Park Comprehensive Cancer Center and allows multiple instant measurements of locally delivered chemotherapy during the procedure without sacrificing lung tissue. When using current techniques, doctors must wait until the regional therapy procedure is over (when the chemo levels have already started to fall) to rush back into the chest to perform a VATS wedge biopsy. Other attempts to measure lung levels during therapy have been unsuccessful. With the present system, SPME needles can be placed in a minimally invasive fashion (as opposed to the open regional lung therapeutic human trials currently underway).

[0046] Provided a research animal will tolerate the device, experiments monitoring drug or biomarker levels w ould be greatly enhanced by additional sampling to increase accuracy and possibly reduce cost and number of animals.

[0047] This type of access approach is potentially a disruptive technology because sampling of the pathologic (e.g., inflamed or cancerous) tissue will allow' laboratory assessmentwith less pain and blood loss, and with similar convenience to phlebotomy. This could allow confirmation of drug delivery' to affected organs and for oncology assessment of tumor response before the changes are manifested on imaging.

[0048] In some embodiments, devices of the present disclosure may be configured for intracorporeal-to-extemal placement (“in-ouf ' embodiments). Such in-out embodiments may be useful for providing access to body cavities (for example, as describe above). In some embodiments, devices of the present disclosure may be configured for outside-in placement. Such outside-in embodiments may be useful for providing access to solid organs.

[0049] In another aspect, the present disclosure may be embodied as a system for accessing a target tissue of an individual. The system includes a sampling needle. The sampling needle may have an absorptive coating. For example, the sampling needle may have an absorptive coating suitable for SPME. The system includes a sheath having a proximal end, a distal end having a flange, and a sampling lumen extending between the distal end and the proximal end. The sampling lumen is configured for passage of the sampling needle from the proximal end and through the flange of the distal end. A sampling head may be configured to be affixed to the proximal end of the sheath, the sampling head having one or more ports providing access to the sampling lumen. The various components of the system (sheath, sampling head, sampling needle, etc.) may have any of the configurations as described above.

[0050] The port of the present disclosure may be used with various devices including, for example, fibers (rigid, semi-rigid, etc.), such as SPME fibers, traditional needles, catheters, such as, for example, micro dialysis catheters, small-bore transducers (e.g. Millar catheters, ultrasonic crystals, etc.), small diagnostic and therapeutic catheters (e.g.. photodynamic sensing and / or delivery probes, etc.) The foregoing are non-limiting examples and other devices may be used with embodiments of the present disclosure.

[0051] Although the present disclosure has been described with respect to one or more particular embodiments, it will be understood that other embodiments of the present disclosure may be made without departing from the spirit and scope of the present disclosure.

Claims

What is claimed is:

1. A device for providing access for sampling a target tissue of an individual, comprising: a sheath having a proximal end, a distal end having a flange, and a sampling lumen extending between the distal end and the proximal end, the sampling lumen configured for passage of a sampling needle from the proximal end and through the flange of the distal end.

2. The device of claim 1, further comprising a sampling head configured to be affixed to the proximal end of the sheath, the sampling head having one or more ports providing access to the sampling lumen.

3. The device of claim 1, further comprising a suction catheter configured for application of a vacuum to the flange of the distal end of the sheath.

4. The device of claim 1. wherein the distal end of the sheath is operable to selectively form the flange.

5. The device of claim 4, wherein the distal end of the sheath comprises a distal tip balloon, sheath dilating balloon, or mechanical tip expander.

6. The device of claim 5, wherein the sheath includes an inflation lumen.

7. The device of claim 1. further comprising a cuff at a location along a length of the sheath to allow ingrowth of surrounding tissue.

8. The device of claim 1, wherein the sheath further comprises a cavity lumen configured to provide access for sampling a fluid of a body cavity.

9. The device of claim 1, further comprising a dilator configured to pass through the sampling lumen.

10. A method for insertion of a sampling catheter, comprising: inserting a needle into a body cavity; inserting a guide wire through the needle and removing the needle from the body leaving the guide wire in place; inserting a dilator into the body cavity over the guide wire; passing a distal end of the guide wire out of the body cavity via a surgical access port;inserting a sheath into the body cavity through the surgical access port by passing a proximal end of a sheath over the distal end of the guidewire and pushing the sheath through the surgical access port; pushing the proximal end of the sheath out of the body cavity over the dilator leaving a flanged distal end of the sheath within the body cavity; and removing the guidewire and dilator.

11. The method of claim 10, further comprising attaching a sampling head to the proximal end of the sheath.

12. The method of claim 11, wherein attaching the sampling head further comprises cutting the sheath to form a new proximal end and attaching the sampling head to the new proximal end.

13. A system for accessing a target tissue of an individual, comprising a sampling needle; a sheath having a proximal end, a distal end having a flange, and a sampling lumen extending between the distal end and the proximal end, the sampling lumen configured for passage of the sampling needle from the proximal end and through the flange of the distal end; and a sampling head configured to be affixed to the proximal end of the sheath, the sampling head having one or more ports providing access to the sampling lumen.

14. The system of claim 13, wherein the sampling needle has an absorptive coating suitable for solid phase microextraction (SPME).

15. A device to provide access for sampling a target tissue of an individual, comprising: a sheath having a proximal end with a sampling head, a distal end configured to be fixed to a tissue, and a sampling lumen extending between the distal end and the proximal end, the sampling lumen configured for passage of a sampling needle via the sampling head at the proximal end and through the distal end.

16. The device of claim 15, further comprising a suction catheter configured for application of a vacuum to a port of the sampling head.

17. The device of claim 15, wherein the distal end of the sheath is configured to be fixed to a tissue by way of a balloon, flange, cuff, suture, or the like.

18. The device of claim 17, wherein the sheath includes an inflation lumen for selectively inflating or deflating the balloon.

19. A system for accessing a target tissue of an individual, comprising a sampling needle; and a sheath having a proximal end with a sampling head, a distal end configured to be fixed to a tissue, and a sampling lumen extending between the distal end and the proximal end, the sampling lumen configured for passage of the sampling needle via the sampling head at the proximal end and through the distal end.

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