WO2013036412A1

WO2013036412A1 - Device and method for accessing small lumen

Info

Publication number: WO2013036412A1
Application number: PCT/US2012/052765
Authority: WO
Inventors: Matthew Ryan; John Dutton
Original assignee: The Children's Hospital Of Philadelphia
Priority date: 2011-09-07
Filing date: 2012-08-29
Publication date: 2013-03-14

Abstract

A device includes a hollow body portion having a proximal end portion, a distal end portion opposite the proximal end portion, and a fluid passage extending between the proximal end portion and distal end portion, The proximal end portion has an outer diameter within a first range, and the distal end portion has an outer diameter withi n a second range. The outer diameter of the proximal end portion may be greater than the outer diameter of the distal end portion. The device may be used for accessing small spaces, such as microvasculature and small luminal structures. In addition, the device may be used in a procedure or with a kit for preparing a 3-D model of a small space, such as the microvascular system of a human or animal.

Description

DEVICE AND METHOD FOR ACCESSING SMALL LUMEN

FIELD

The present invention relates generally to devices for cannulating vessels and spaces in the body, and more specifically to a device, method and kit for accessing microvasculature and other structures in the body having very small lumen,

BACKGROUND

There has been growing interest in the ability to access microvasculature and other small lumen using a device that can be inserted into the lumen. Unfortunately, existing devices and methods are not designed to access tiny vessels, ducts or bronchioles. Fine needle syringes and cannulae are too large in diameter to access microvasculature. In addition, needles and cannulae have relatively thick walls with sharp edges that easily puncture microvasculature.

Researchers working with laboratory mice have attempted to cannulate microvasculature and biliary systems using PE-10 surgical tubing. The tubing is stretched to reduce the tubing diameter. PE-10 tubing is difficult to stretch, however, and stretching can easily snap the tubing. In addition, stretched PE-10 tubing can only stretch so far before the lumen becomes constricted or closed. Moreover, surgical tubing is difficult to cannulate into a microvasculature system because it loses cross-sectional stability or rigidity after it is stretched. Stretched tubing tends to bunch up or buckle when advanced into small vessels.

Because there are no readily available devices for accessing microvasculature and other small lumen in-vivo, some investigators who perform research on mice choose to wait for the mice to age at least 120 days before attempting to access the luminal space. See, e.g. Sparks, Erin E., et al. "Notch Signaling Regulates Formation of the Three- Dimensional Architecture of Intrahepatic Bile Ducts in Mice", Hepatology, Vol. 51, Issue 4, April 2010. At this age, the lumen is large enough to be cannulated. This delayed approach prevents the researcher from studying the animal's anatomy during the animal's growth phase. This missed opportunity can prevent researchers from

identifying and studying early on-set diseases. Having to wait for laboratory animals to reach a proper age delays important research, and consequently, the publication of important research. Waiting for the animals to age also increases costs associated with housing the animals while they grow to the proper size.

Based on the foregoing, conventional devices and procedures for accessing vasculature fall short of the needs of researchers and others who desire to access microvasculature and other structures having small lumen. SUMMARY

The drawbacks of conventional devices and procedures for accessing vasculature are addressed in several respects by devices and procedures in accordance with this description.

In one embodiment, a device includes a hollow body portion having a proximal end portion, a distal end portion opposite the proximal end portion, and a fluid passage extending between the proximal end portion and distal end portion. The proximal end portion has an outer diameter within a first range, and the distal end portion has an outer diameter within a second range. The outer diameter of the proximal end portion may be greater than the outer diameter of the distal end portion. The device may be used for accessing small spaces, such as microvasculature and small luminal structures. In addition, the device may be used in a procedure or with a kit for preparing a 3-D model of a small space, such as the microvascular system of a human or animal.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing summary and the following description will be better understood in conjunction with the drawing figures, of which :

Figure 1 is a perspective view of a kit in accordance with one exemplary embodiment of the invention;

Figure 2 is a schematic view of an image generated using kits and devices in accordance with the invention;

Figure 3 is a perspective view of a n access device included in the kit of Figure 1 ; Figure 4 is a perspective view of another access device in accordance with the invention;

Figure 5 is a perspective view of another access device in accordance with the invention ;

Figure 6 is a perspective view of another access device in accordance with the invention;

Figure 7 is a perspective view of another access device in accordance with the invention; and

Figure 8 is a perspective view of another access device in accordance with the invention.

DETAILED DESCRIPTION

Although the invention is illustrated and described herein with reference to specific embodiments, the invention is not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims and without departing from the invention.

In one embodiment, a device for accessing microvasculature and small luminal structures includes a hollow body portion having a proximal end portion, a distal end portion opposite the proximal end portion, and a fluid passage extending between the proximal end portion and distal end portion. The proximal end portion has an outer diameter between about 0.15 mm and about 0.25 mm, and the distal end portion has an outer diameter between about 0.05 mm and about 0.15 mm.

In another embodiment, the device may include a hollow needle and a hollow flexible tube. The flexible tube has a first end and a second end, the first end connected to the needle, and the second end connected to the proximal end portion of the body portion, the flexible tube interconnecting the body portion and the needle in fluid communication.

In another embodiment, the body portion of the device may be formed of glass. In addition, the body portion may include a hollow middle portion between the proximal end portion and the distal end portion. The middle portion may have an outer diameter greater than the outer diameters of the proximal end portion and distal end portion. For example, the middle portion may have an outer diameter between about 1.0 mm and about 2.0 mm. The middle portion may also enclose a sample collection space.

In another embodiment, the body portion may define a longitudinal axis extending between the proximal end portion and the distal end portion . The distal end portion of the device may be bendable through an angle of 45 degrees with respect to the longitudinal axis of the body portion.

In another embodiment, a method of cannulating a small lumen includes the step of inserting a tubular device into a lumen, the device featuring a hollow body portion having a proximal end portion, a distal end portion opposite the proxima l end portion, and a fluid passage extending between the proximal end portion and distal end portion . The proximal end portion may have an outer diameter between about 0.15 mm and about 0.25 mm, and the distal end portion may have an outer diameter between about 0.05 mm and about 0.15 mm. The device may include a hollow flexible tube connected to the proximal end portion of the body portion. The device may further include a needle connected to the flexible tube.

In another embodiment, the method may include the step of preparing a cast of the small lumen using the device. The step of preparing a cast may include the step of injecting a compound through the device and into the lumen, and allowing the compound to set. The method may also include inserting the distal end portion through the wall of a vessel surrounding the lumen and advancing the distal end portion to a desired location in the lumen. In addition, the method may include the step of securing the distal end portion at the desired location i n the lumen. The step of securing the distal end portion at the desired location in the lumen may include tying a suture around the vessel wall and distal end portion.

In another embodiment, a kit for preparing a 3-D model of a microvascular system may include a microvasculature access device having a hollow body portion . The body portion may include a proximal end portion, a distal end portion opposite the proximal end portion, and a fluid passage extending between the proximal end portion and distal end portion. The kit may also include a hollow needle and a hollow flexible tube. The needle may be a 30 gauge needle. The flexible tube may include a first end and a second end, the first end connectable to the needle, and the second end connectable to the proximal end portion of the body portion.

In another embodiment, the proximal end portion may have an outer diameter between about 0.15 mm and about 0.25 mm, and the distal end portion may have an outer diameter between about 0.05 mm and about 0.15 mm. For example, the proximal end portion may have an outer diameter of about 0.2 mm and the distal end portion may have an outer diameter of about 0.1 mm. The kit may further include one or more compounds for preparing a cast. For example, the kit may include a silicon resin.

Referring now to Figure 1, a kit 10 is ihown in accordance with one exemplary embodiment of the invention. Kits in accordance with the invention can be used to access small lumen for a variety of purposes and applications. For example, kits in accordance with the invention can be used to access ducts, bronchioles, lymphatic systems, renal tubules, airways or other spaces. In addition, kits in accordance with the invention can be used for preparing casts of small spaces, aspirating small spaces, or other functions. In this example, kit 10 is used to construct a three-dimensional cast for use as a model for visualizing and studying small structures in the body.

Kit 10 includes an access device 100, a length of tubing 200, a needle 300 and a silicon resin compound 400 to be administered through the needle, tubing and device. Needle 300 is a 30 gauge needle with female luer connector. Compound 400 can be perfused into small lumen and allowed to set to create a 3-D cast of small structures. The cast can be removed from the surrounding tissue and scanned using X-ray computed tomography or other imaging method to create a 3-D image of the structure. Figure 2 provides a schematic line illustration of one such scan. The scan was taken from a cast made by perfusing a silicon resin compound into the liver of a mouse using a devices and methods in accordance with the invention .

Access device 100 is attached to a first end 210 of tubing 200 with an adhesive 250. Syringe 300 is attached to a second end 220 of the tubing with adhesive 260, which may or may not consist of the same material contained in adhesive 250.

Adhesives 250 and 260 join the components together and provide seals at the tubing ends that prevent fluid from leaking out of the tubing. Tubing 200 provides a link between device 100 and needle 300, so that the needle can be operated away from the device. In this arrangement, tubing 200 keeps the bulkier needle 300 and other objects away from the work area in the immediate vicinity of the patient or subject. This allows the work area around device 100 to remain clear and uncluttered. Tubing used in accordance with the invention may be formed of any material suitable for the intended use. In kit 10, the tubing 200 is made of PE-10 laboratory tubing having an inner diameter of about 0.3 mm, an outer diameter of about 0.64 mm and a length of about 45.7 cm.

Referring to Figure 3, device 100 is shown in more detail. Device 100 is designed to provide an access port into anatomical structures having very small passages, such as microvasculature, or the biliary tree in the liver. Unlike syringes and catheters, which are much larger in diameter, device 100 can be inserted into and navigated through small lumen without rupturing vessel walls or tissues that surround the lumen. As such, device 100 can be used as an adapter that allows much bulkier devices, like syringes and catheters, to be fluidly connected to very small lumen. The small size allows device 100 to cannulate microvasculature of mice as young as 17.5 days, which compares favorably to prior devices and methods that require the mice to mature to an age of 120 days.

Device 100 includes an elongated tubular body portion 110. Body portion 110 has a proximal end portion 120 and a distal end portion 130. During use, the proximal end portion 120 is configured for connection to tubing and/or other devices. The distal end portion 130 is configured for insertion into a small lumen. Proximal end portion 120 forms a proximal opening 122 and distal end portion 130 forms a distal opening 132. A longitudinal axis X extends between the center of proximal opening 122 and the center of distal opening 132. For purposes herein, the term "longitudinal axis" means an axis that interconnects the center point taken at each cross section of an object through its longest dimension. Proximal end portion 120 and distal end portion 132 are aligned coaxially with one another along longitudinal axis X. A fluid passage 134 extends between the proximal opening 122 and distal opening 132.

Device 100 offers a unique combination of small diameter size, rigid cross section, and longitudinal flexibility. The small diameter size allows the device 100 to access very small lumen. Preferably, proximal end portion 120 has a diameter between about 0.15 mm to about 0.25 mm. More preferably, proximal end portion 120 has a diameter between about 0.19 mm to about 0.21 mm. Distal end portion 130 preferably has a diameter between about 0.05 mm to about 0.15 mm. More preferably, distal end portion 130 has a diameter between about 0.09 mm to about 0.11 mm. The small diameter of distal end portion 130 prevents the end of the tube from puncturing vessel walls or tissue surrounding the lumen. The rigid cross section allows the device 100 to resist collapsing, buckling or folding, which can create a blockage in the device that prevents the flow of fluid in fluid passage 134.

Longitudinal flexibility allows the device 100 to bend when needed . To provide

5 flexibil ity for bending, the proximal and distal end portions 120 and 130 have lengths that are much longer than their respective diameters. For example, length L_P of proximal end portion 120 may be 1.3 cm or longer. Length L_D of distal end portion 130 may be 3.8 cm or longer. Shorter lengths also work, but longer lengths generally provide a larger range of bending motion, which may be desirable i n certain procedures. In l o preferred embodiments, the proximal and distal end portions are each bendable up to 45 degrees with respect to longitudinal axis X. The small diameter size of distal end portion 130, combined with its cross-sectional rigidity and longitudinal flexibility, allow s the distal end portion to bend easily to follow a vessel, while maintaining structu ral integrity without shattering, and while keeping fluid passage 134 open to allow fluids to be i s introduced into the lumen, or drawn out of the lumen, depending on the application .

Access devices in accordance with the invention may be formed of glass, fiberglass or other materials that provide a substantially rigid tubular body that maintains or substantially maintains its cross sectional shape, thus keeping the fluid passage open when the device is bent or subjected to radial compression forces. Device

20 100, for example, is formed of glass. Glass is inert and has minimal reaction to

chemicals, solvents and drugs. In addition, glass is dimensionally stable, with a very low coefficient of expansion . Moreover, glass tubing can be drawn to provide inner and outer diameters that are controllable with a very high degree of precision. Some

manufacturing processes are capable of controlling the inner and outer diameter to

25 within ±0.001 mm. Once drawn to small diameters, glass tubing is very flexible for

bending, while maintaining a rigid cross section that resists collapse, kinking or buckling .

Devices in accordance with the invention may include a variety of design features between the proximal and distal end portions to address different needs. For example, devices in accordance with the invention may include a larger diameter chamber

30 between the end portions to collect fluid samples, or to serve as a flashback chamber, A larger diameter section between the end portions can also provide a central gripping a rea that can be used when handling the device. Device 100 includes a middle portion 150 having a larger diameter suitable for collecting fluid. Middle portion 150 has a diameter of about 1.25 mm and a length of about 3.8 cm .

35 In one method of manufacture, a device in accordance with the invention is made by heating glass tubing having a diameter of 1.25 mm. A first end portion is heated until the first end portion becomes malleable. The tubing is then removed from the heat source, and the first end portion is stretched or drawn in the longitudinal direction so that the inner and outer diameters of the first end portion decrease. The first end portion is drawn until the outer diameter of the first end portion is approximately 0.2 mm. The second end portion of the tubing is heated in the same manner and drawn until the outer diameter of the second end portion decreases to approximately 0.1 mm. If desired, a middle portion of a desired length can be left intact with the original diameter of 1.25 mm. The length of the middle portion can be controlled by choosing the spacing between the first and second end portions, and controlling the locations where the tubing is heated and stretched.

After the glass cools, the ends of the first and second end portions are trimmed so that each end portion has a desired length. This process creates three distinct sections along the tubing : a first end portion having an outer diameter of about 0.2 mm, a middle portion having an outer diameter of about 1.25 mm, and a second end portion having an outer diameter of about 0.1 mm. The finished length of the first end portion may be 1.3 cm, the finished length of the middle portion may be 3,8 cm, and the finished length of the second end portion may be 3.8 cm.

Referring now to Figure 4, an access device 500 is shown in accordance with another embodiment of the invention. Device 500 includes a structure similar to device 100, but the three sections are assembled from separate sections. The structure includes a proximal end portion 520, distal end portion 530 and middle portion 550 that are joined together end to end. This embodiment provides the advantage of using different materials to make the individual sections. For example, proximal end portion 520 and middle portion 550 may be formed from plastic, while distal end portion 530 may be formed of glass.

Assembled devices in accordance with the invention may include end portions that are connected to middle portions with permanent connections, such as glued

connections. Alternatively, one or both end portions may be connected to the middle portion with a detachable connection. Detachable connections may include, but are not limited to luer fittings or elastic membranes that are pierced by the proximal and distal end portions, In Figure 4, proximal end portion 520 is connected to middle portion 550 by piercing the end of the proximal end portion 520 through an elastomeric membrane or seal 560 in a first side 552 of middle portion. A similar seal 570 is positioned on the second side 554 of middle portion to connect the middle portion to distal end portion 530.

Assembled embodiments with detachable connections, like that shown in Figure 4, provide the option of using interchangeable sections . For example, middle portion 550, which can be used for sample collection, can be removed and replaced with another 3 middle portion that performs a different function. For example, middle section 550 can be removed and replaced with a small vial containing a solid or liquid component to be mixed with a fluid being injected through the device.

Referring now to Figure 5, an access device 600 is shown in accordance with another embodiment of the invention. Device 600 features a proximal end portion 620 connected directly to a distal end portion 630, with no middle portion in between.

Thus far, the proximal and distal end portions have been shown and described as straight linear configurations when in relaxed or undetected states. The proximal and distal end portions need not have straight configurations, however. Distal end portions may have a variety of non-linear configurations that are pre-formed so that the distal end portions are non-linear in a relaxed state. For example, distal end portions may have U-shapes, hook shapes, or one or more bends. Non-linear configurations may be better suited for certain vessels or spaces of interest. For example, the hepatic artery in mice extends from the liver and bends sharply. A straight distal end portion is not ideal for accessing this artery. Pre-formed non-linear configurations allow a distal end portion to be flexed as needed to reach a point in a vessel, and then return to a non-linear configuration that matches or more easily adapts to the non-linear path at that location. Non-linear configurations allow devices to cannulate vessels in a way that allows the vessels to remain free of added stress and tensions as the distal end portion is advanced into the vessel. Too much stress or tension can tear vessels, particularly small vessels like the hepatic artery. Non-linear configurations can also allow for better angles of access that require the removal of less tissue than a straight distal end portion. This reduces the amount of dissection needed, which preserves architecture and saves time.

Pre-formed non-linear configurations can also be used as a means for visually distinguishing different devices that are used in close proximity to one another. For example, a device having one non-linear configuration can be used to access one region of the liver, and another device having a different and distinctive non -linear configuration can be used to access a separate region of the liver.

Referring to Figure 6, an access device 700 with a non-linear distal end portion is shown in accordance with another embodiment of the invention. Device 700 features a proximal end portion 720, a distal end portion 730 and a middle portion 750. Distal end portion 730 includes a first section 732 having a first linear orientation and a second section 734 having a second linear orientation that is offset from the orientation of the first section by an angle of about 135 degrees.

Figure 7 shows an access device 800 with a non-linear distal end portion in accordance with another embodiment of the invention. Device 800 features a proximal end portion 820, a distal end portion 830 and a middle portion 850. Distal end portion 830 includes a first section 832 having a first linear orientation and a second section 834 having a second linear orientation that is offset from the orientation of the first section by an angle of about 45 degrees.

It will be understood that distal end portions may be pre-formed with first and

5 second sections that are angularly offset from one another by angles other than 45

degrees or 135 degrees. First and second sections may be offset by any angles between 0 degrees and 180 degrees. When a distal end portion is pre-formed with an offset angle between the first and second sections, the distal end portion preferably is flexible enough to bend or deform to other angles, shapes and configurations, including a straight lo configuration. The distal end portion preferably has sufficient elasticity to return the distal end portion to the pre-formed angle when stress is removed from the distal end portion.

Figure 8 shows an access device 900 with a non-linear distal end portion in accordance with another embodiment of the invention. Device 900 features a proximal i s end portion 920, a distal end portion 930 and a middle portion 950. Distal end portion 930 has a "looped" configuration formed by a first section 932, a second section 934 and a third section 936. Second section 934 is bent at an angle between 0 degrees and 90 degrees relative to the orientation of the first section 932. Likewise, third section 936 is bent at an angle between 0 degrees and 90 degrees relative to the orientation of the

20 second section 934. Third section 936 extends back toward middle portion 950 and

intersects first section 932, forming a looped configuration.

Instead of the intersecting with first section 932, third section 936 may extend parallel to first section in a U -shaped configuration. Either a U-shaped configuration or a looped configuration can be used for sample collection, suction of fluid in a cavity, or

25 perfusion of casting compounds.

While preferred embodiments of the invention have been shown and described herein, it will be understood that such embodiments are provided by way of example only. Numerous variations, changes and substitutions will occur to those skilled in the art without departing from the scope of the invention. For example, the inner and outer

30 diameters of the proximal and distal end portions may vary from those described above, depending on the intended use. Where larger tubing is preferred for example, the proximal end portion may have a larger outer diameter. Accordingly, it is intended that the appended claims cover all such variations as fall within the scope of the invention.

Claims

CLAIMS What is Claimed ;

1. A device for accessing microvascu lature comprising :

a hollow body portion comprising a proximal end portion, a distal end portion 5 opposite the proximal end portion, and a fluid passage extending between the proximal end portion and distal end portion, the proximal end portion having an outer diameter between about 0, 15 mm and about 0.25 mm, and the distal end portion having an outer diameter between about 0.05 mm and about 0.15 mm;

a hollow needle; and

l o a hollow flexible tube having a first end and a second end, the first end connected to the needle, and the second end connected to the proximal end portion of the body portion, the flexible tube interconnecting the body portion and the needle in fluid communication.

2. The device of claim 1, wherein the body portion is formed of glass.

is 3. The device of claim 1, wherein the body portion comprises a hollow middle portion between the proximal end portion and the distal end portion, the middle portion having an outer diameter greater than the outer diameters of the proximal end portion and distal end portion.

4. The device of claim 3, wherein the middle portion has an outer diameter0 between about 1.0 mm and about 2.0 mm.

5. The device of claim 3, wherein the middle portion encloses a sample collection space.

6. The device of claim 1, wherein the body portion defines a longitudinal axis extending between the proximal end portion and the distal end portion, the distal end5 portion bendable through an angle of 45 degrees with respect to the longitudinal axis of the body portion.

7. The device of claim 1 , wherein the distal end portion comprises a first section and a second section extending at an angle with respect to the first section.

8. The device of claim 7, wherein the second section extends at an angle of0 between about 90 degrees and about 180 degrees with respect to the first section.

9. The device of claim 7, wherein the second section extends at an angle of about 45 degrees with respect to the first section.

10. The device of claim 7, wherein the second section extends at an angle of about 135 degrees with respect to the first section.

5 11. The device of claim 7, wherein the distal end portion further comprises a third section extending from the second section, the first, second and third sections forming a loop.

12. A method of cannulating a small lumen, the method comprising inserting a tubular device into a lumen, the device comprising a hollow body portion having a proximal end portion, a distal end portion opposite the proximal end portion, and a fluid passage extending between the proximal end portion and distal end portion, the

5 proximal end portion having an outer diameter between about 0.15 mm and about 0.25 mm, and the distal end portion having an outer diameter between about 0.05 mm and about 0.15 mm.

13. The method of claim 12 wherein the device comprises a hollow flexible tube connected to the proximal end portion of the body portion.

10 14. The method of claim 13, wherein the device comprises a needle connected to the flexible tube.

15. The method of claim 12, further comprising the step of preparing a cast of the small lumen using the device.

16. The method of claim 15, wherein the step of preparing a cast of the small i s lumen comprises the step of injecting a silicon resin through the device and into the lumen, and allowing the silicon resin to set.

17. The method of claim 12, wherein the step of inserting a tubular device into a lumen comprises inserting the distal end portion through the wall of a vessel surrounding the lumen and advancing the distal end portion to a desired location in the

20 lumen.

18. The method of claim 17, further comprising the step of securing the distal end portion at the desired location in the lumen.

19. The method of claim 18, wherein the step of securing the distal end portion at the desired location in the lumen comprises tying a suture around the vessel wall and

25 distal end portion.

20. A kit for preparing a 3-D model of a microvascular system, the kit comprising :

a microvasculature access device comprising a hollow body portion with a proximal end portion, a distal end portion opposite the proximal end portion, and a fluid 30 passage extending between the proximal end portion and distal end portion;

a hollow needle; and

a hollow flexible tube having a first end and a second end, the first end connectable to the needle, and the second end connectable to the proximal end portion of the body portion.

35 21. The kit of claim 20, wherein the proximal end portion has an outer

diameter between about 0.15 mm and about 0.25 mm, and the distal end portion has an outer diameter between about 0.05 mm and about 0.15 mm.

22. The kit of claim 20, wherein the proximal end portion has an outer diameter of about 0.2 mm and the distal end portion has an outer diameter of about 0.1 mm.

23. The kit of claim 20 further comprising a compound for preparing a cast.

24. The kit of claim 23, wherein the compound comprises a silicon resin.

25. The kit of claim 20, wherein the needle comprises a 30 gauge needle.