CN115955941A

CN115955941A - Device for biological cell collection and method of use

Info

Publication number: CN115955941A
Application number: CN202080102043.4A
Authority: CN
Inventors: 阿米塔巴·恰克; 桑多德·马科维茨; 丹尼斯·西德拉克; 约瑟夫·威利斯; 里山·阿克洛格; 迈克尔·布蒂莱特; 理查德·亚兹贝克
Original assignee: Case Western Reserve University
Current assignee: Case Western Reserve University
Priority date: 2020-06-16
Filing date: 2020-06-16
Publication date: 2023-04-11
Also published as: JP2023536683A; AU2020453916A1; CA3186131A1; WO2021257058A1; EP4164503A4; EP4164503A1

Abstract

A device for collecting a biological sample in a patient, the device comprising: an expandable portion attached to the tubular member and designed to expand from within the tubular member and retract into the tubular member when expanded; a surface on the expandable portion, the surface being provided with a variable thickness to facilitate movement of the expandable portion between the expanded and retracted states; and a plurality of protrusions on the surface that allow collection of a biological sample when the expandable portion is in the expanded state.

Description

Device for biological cell collection and method of use

Government funding

The invention was made with government support awarded by the national institutes of health under grant numbers P50CA150964, U01CA152756, U54CA 163060. The united states government has certain rights in this invention.

Technical Field

The present disclosure relates to systems and methods suitable for collecting biological samples. In particular, the present disclosure relates to a biological sample collection device comprising an expandable device that may be designed for collecting a sample and retracting into a proximal end portion.

Background

Generally, known tissue collection devices include expandable devices having longitudinally extending folds. The expandable device radially expands at a trapping site within a body lumen, such as the esophagus. After expansion of the device, tissue is collected from the collection site. After the tissue is collected, the expandable device is collapsed. The fold captures the collected tissue when the device is collapsed after collecting the tissue. Known tissue collection devices may be inserted endoscopically to a collection site or via standard catheter intubation techniques.

Disclosure of Invention

There is a need for improvements in the collection of biological samples. In various embodiments, the present disclosure provides solutions to this need, in addition to having other desirable characteristics. The present disclosure relates to a device for collecting a biological sample, and more particularly, to a device for collecting a biological sample such as tissue, cells, proteins, RNA and/or DNA from the esophagus of a subject.

According to an exemplary embodiment of the present invention, a device for collecting a biological sample from a subject is provided. The device includes: an expandable portion attached to the tubular member and designed to expand from within the tubular member and retract into the tubular member when expanded; a surface on the expandable portion, the surface being provided with a variable thickness to facilitate movement of the expandable portion between the expanded and retracted states; and a plurality of protrusions on the surface that allow collection of a biological sample when the expandable portion is in the expanded state.

According to aspects of the invention, the variable thickness is defined by a thinner distal end of the expandable portion relative to a proximal end of the expandable portion. The variable thickness is defined by a collapsible fold positioned circumferentially around a surface of the expandable portion. The expandable portion may include a plurality of different levels of stiffness to facilitate a combination of expansion, contraction, and retraction. The expandable portion is removable from and replaceable on the tubular member using at least one of a friction fit or a mechanical fit. The variable thickness may be defined by a ridge positioned circumferentially around the surface of the expandable portion. A plurality of ridges may be positioned between each row of the plurality of projections to vary the expanded size and shape of the expandable portion. The plurality of ridges may facilitate collection of a biological sample. The expandable portion may include a stretch extending along a length of each row of the plurality of protrusions to create a variable stiffness of the expandable portion. The tubular member may be a catheter coupled to the expandable portion at a proximal end and coupled to the connector at a distal end.

According to aspects of the present invention, the connector may be a Y-fitting having a first leg extending at an angle to a second leg of the connector, the second leg including a stopcock valve. The expandable portion may have an outer surface facing radially outward when the expandable portion is in the expanded state and radially inward when the expandable portion is in the retracted state. The first sidewall of the tissue collection projection may extend generally perpendicular to the outer surface of the expandable portion when the expandable portion is in the non-expanded position between the retracted position and the expanded position, and the second sidewall of the tissue collection projection tapers toward the first sidewall as the sidewall extends radially outward from the outer surface. At least one of the plurality of protrusions may have a V-shape, with a first sidewall facing in a proximal direction and forming an inner wall of the V-shape, and a second sidewall facing in a distal direction and forming an outer wall of the V-shape. The expandable portion has a hardness between 20 shore a and 70 shore a. The device may further comprise a cap extending over the expandable portion when the expandable portion is in the retracted position to retain the expandable portion in the retracted position. The expanded state may be facilitated by the presence of positive pressure. The retracted state may be facilitated by the presence of a negative pressure.

Drawings

These and other features of the present disclosure will be more fully understood by reference to the following detailed description in conjunction with the accompanying drawings, in which:

FIG. 1 is a schematic view of a biological sample collection device constructed in accordance with the present disclosure;

FIG. 2 is a schematic view of the collection device of FIG. 1 shown in a collapsed position;

FIG. 3 is a cross-sectional view of the collection device of FIG. 2;

FIG. 4 is an enlarged plan view of a projection or riser of the collection device of FIG. 1;

FIG. 5 is a cross-sectional view of the tab taken along line 5-5 in FIG. 4;

FIG. 6 is an enlarged plan view of the tab shown after expansion of a portion of the collection device;

FIG. 7 is a schematic view of the tab after expansion of a portion of the collection device taken along line 7-7 in FIG. 6;

FIG. 8 is a schematic view of the collection device showing the stylet and connector of the collection device;

FIG. 9 is an enlarged schematic view of the connector of FIG. 8;

FIG. 10 is a schematic cross-sectional view of a collection device constructed in accordance with another embodiment of the present disclosure;

FIG. 11 is a schematic view of a collection device constructed in accordance with a third embodiment of the disclosure;

FIG. 12 is a schematic cross-sectional view of a collection device constructed in accordance with a fourth embodiment of the present disclosure;

FIG. 13 is a schematic cross-sectional view of a collection device constructed in accordance with a fifth embodiment of the present disclosure;

FIG. 14 is a schematic cross-sectional view of a collection device constructed according to an example embodiment of the disclosure;

FIG. 15 is a schematic cross-sectional view of a collection device constructed in accordance with an example embodiment of the disclosure;

FIG. 16 is a schematic cross-sectional view of a collection device constructed in accordance with an example embodiment of the disclosure;

FIG. 17 is a schematic cross-sectional view of a collection device constructed in accordance with an example embodiment of the disclosure; and is

Fig. 18 is a schematic cross-sectional view of a collection device constructed in accordance with an example embodiment of the disclosure.

Detailed Description

In some embodiments, the devices of the present disclosure can be used to collect a biological sample in a subject. The device may include an expandable distal end portion attached to the tubular support member. The expandable distal end portion may be designed to expand from within a proximal end portion that is coupled to or part of the tubular support member. The expandable distal end portion may expand outwardly from the proximal end portion, expand outside of the proximal end portion, and retract into the proximal end portion upon contraction. In some embodiments, a surface on the expandable distal end portion may be provided with a variable level of thickness to facilitate movement of the expandable distal end portion between the expanded and retracted states. The variable thickness of the expandable distal end portion may be configured to facilitate any combination of expansion, contraction, and retraction of the expandable distal end portion relative to the proximal end portion. The variable thickness may also affect the shape and flexibility/rigidity of the expandable distal end portion when in any combination of expansion, contraction and retraction in the expandable state. In some embodiments, the surface of the expandable distal end portion may include a plurality of protrusions or standoffs positioned thereon to allow collection of a biological sample while the expandable distal end portion is in the expanded state. Protrusions or risers positioned on the surface can also be accompanied by structures (e.g., ridges, valleys, etc.) formed by the variable thickness of the expandable distal end portion.

Fig. 1-18 illustrate an example embodiment or example embodiments for an improved operation for collecting a biological sample according to the present disclosure, wherein like components are designated by like reference numerals throughout. Although the present disclosure will be described with reference to an example embodiment or embodiments illustrated in the drawings, it should be understood that the present disclosure may be embodied in many alternate forms. Those of skill in the art will also appreciate different ways of varying parameters, such as size, shape, or type of elements or materials, of the disclosed embodiments in a manner that still meets the spirit and scope of the present disclosure.

A collection device 10 for collecting a biological sample constructed in accordance with the present disclosure is illustrated in fig. 1-9. The collection device 10 may be used to collect tissue, cells, proteins, RNA and/or DNA from a body cavity, such as the esophagus of a subject. As discussed herein, the use of the term subject may refer to any other combination of a human patient, an animal subject, or an object that may have a portion that needs to be sampled. The tissue, cells, proteins, RNA and/or DNA collected from the esophagus may be used in any of the methods disclosed in the following applications: U.S. patent application Ser. No. 14/109,041, U.S. patent application Ser. No. 13/670,155, U.S. patent application Ser. No. 13/263,020, U.S. patent No. 8,642,271, U.S. patent No. 8,481,707, U.S. patent No. 8,415,100, U.S. patent No. 8,221,977, U.S. patent No. 7,964,353, U.S. patent No. 7,485,420, and U.S. patent No. 10,660,621, the entire contents of which are incorporated herein by reference.

The collecting device 10 comprises a substantially hollow longitudinally extending collecting portion 12. The collecting portion 12 has a first or proximal axial end portion 14 connected to a second or distal end portion 16. The distal end portion 16 has a first axial end portion 22 connected to the proximal axial end portion 14. The first end portion 22 may be connected to the proximal end portion 14 in any desired manner, such as by using an adhesive or bonding agent. The first axial end portion 22 engages a shoulder 24 on the proximal axial end portion 14. Thus, the collecting section 12 has a smooth outer surface. The distal axial end portion 16 may be connected to the proximal end portion 14 in any desired manner. The proximal axial end portion 14 and the distal axial end portion 16 may be made of a flexible polymer, such as silicone or polyurethane. The distal axial end portion 16 has a lower hardness than the proximal axial end portion 14. The distal axial end portion 16 may have a hardness between 5 shore a and 90 shore a. The hardness of the distal axial end portion 16 is preferably between 20 shore a and 70 shore a, and more particularly, is about 30 shore a.

The distal axial end portion 16 can expand and contract. The first or proximal axial end portion 14 is relatively rigid. Thus, the proximal end portion 14 has a fixed radial extent. The first and second

axial end portions

14, 16 may be formed as separate pieces that are connected together in any desired manner, or may be integrally formed as one piece. Although the axial end portion 14 is illustrated as having a cylindrical shape, the proximal end portion may have any desired shape.

The proximal axial end portion 14 is connected to a support member 20, such as a catheter. The support member 20 may be a tubular member in fluid communication with the interior of the collecting section 12. The proximal axial end portion 14 directs fluid, such as air, from the support member 20 to the distal axial end portion 16. The support 20 resists telescoping when a vacuum is applied to the support member and stretching during withdrawal of the collection device 10 from the collection site.

The second or distal end portion 16 of the collecting portion 12 has an expanded or inflated position (fig. 1) and a collapsed or contracted position (fig. 2-3). The expanded position shown in fig. 1 may be one of many expanded positions for the distal end portion 16. It is contemplated that the distal end portion 16 may expand more than shown in fig. 1, such that the distal end portion obtains a more spherical shape and looks like a hot air balloon. As shown in fig. 1, the distal end portion 16 has a convex shape when in the expanded or inflated position. When in the expanded position, the distal end portion 16 may extend radially outward a greater distance than the proximal end portion 14.

As shown in fig. 2 and 3, the distal end portion 16 extends into the first or proximal axial end portion 14 and has a concave shape when in the collapsed or retracted position. When in the collapsed position, the distal end portion 16 may be retracted. When in the collapsed or retracted position, the distal end portion 16 extends axially into the interior of the proximal end portion 14. Thus, the distal end portion 16 moves axially or longitudinally relative to the proximal end portion 14 when moving between the contracted and expanded positions. The relatively low stiffness of the distal end portion 16 allows the distal end portion to extend axially into the interior of the proximal end portion 14 and have a concave shape when in the collapsed position. The distal end portion 16 may be biased into the collapsed or retracted position in any desired manner.

The proximal end portion 14 has a relatively high stiffness such that it does not collapse when a vacuum is applied to the proximal end portion through the support 20. The shape of the proximal end portion 14 does not change as the distal end portion 16 moves between the contracted and expanded positions. The proximal end portion 14 does not move radially when the distal end portion 16 moves between the contracted position and the expanded position.

The distal end portion 16 has an outer surface 32, the outer surface 32 being for collecting tissue when the distal end portion is in the expanded position. The outer surface 32 faces radially outward when the distal end portion 16 is in the expanded position, and may face radially inward when the distal end portion 16 is in the collapsed or retracted position. It is contemplated that outer surface 32 of distal end portion 16 may have any desired configuration for collecting tissue. The outer surface 32 of the distal end portion 16 may have a plurality of projections or standoffs 40 for collecting tissue. The distal end portion 16 may have any desired number of projections or upstands 40.

The projections or upstands 40 may have a V-shape (fig. 4). Each tab 40 has a first side 42 and a second side 44 extending from an intersection 48. The first and second sides 42, 44 extend in a generally proximal direction from the intersection 48 when the distal end portion 16 is in the expanded position (fig. 1). The first and second sides 42, 44 extend in a generally distal direction when the distal end portion 16 is in a collapsed or retracted position (fig. 2 and 3). The first and second sides 42, 44 define a cup 50 for receiving a collected biological sample. The cup 50 faces in the proximal direction when the distal section 16 is in the expanded position and in the distal direction when the distal section is in the collapsed position.

The first and second sides 42, 44 may extend at an angle of approximately 90 ° relative to each other. It is contemplated that the first and second side portions 42, 44 may extend at any desired angle relative to one another. The desired angle may be determined based on the type of biological sample to be collected. Alternatively, the projection 40 may be cup-shaped or have a semi-circular shape.

Each of the projections or upstands 40 has side walls 54 and 56 (fig. 5), the

side walls

54 and 56 extending radially outwardly from the outer surface 32 when the distal portion 16 is in the expanded position. The sidewall 56 faces in the proximal direction when the distal portion is in the expanded position and forms the inside of the cup 50. The sidewall 54 faces in the distal direction when the distal portion is in the expanded position and forms an outer wall of the cup 50. Sidewalls 54 and 56 extend from outer surface 32 to a radially outer surface 58 of projection 40. When distal end portion 16 is in the unexpanded position between the expanded position and the collapsed position, sidewalls 56 extend substantially perpendicular to outer surface 32 and outer surface 58 of tab 40. When the distal end portion 16 is in the non-expanded position, the sidewall 54 tapers toward the sidewall 56 as the sidewall 54 extends from the outer surface 32 toward the radially outer surface 58 of the projection 40.

The side walls 56 may form a flap, hood, or lip 59 (fig. 6-7) when the distal end portion 16 is in the expanded position. The lip 59 aids in collecting the sample for the collection site. A lip 59 extends from the outer surface 58 of the projection 40 towards the proximal end portion 14. The projection 40 elongates from the shape shown in fig. 4 to the shape shown in fig. 6 during expansion of the distal end portion 16. The protrusion 40 also reduces the height from the shape shown in fig. 1 to the shape shown in fig. 7 during expansion of the distal end portion 16. The elongation and reduction in height of the projection 40 causes a collection lip 59 to be formed on the collection side of the projection 40. The difference in taper between the

side walls

54, 56 produces a biased incline of the wall portion to roll up toward the side wall 56. In the non-expanded state, the tabs 40 are offset and concave on the side walls 56, and this is further enhanced during expansion. When elongation of the tab 40 occurs, the tab becomes thinner and less stable to hold in a vertical column, which causes the top edge to roll over toward the sidewall 56, forming a lip 59 on the proximal or collection side of the tab. Both sidewalls 54, 56 may taper at any desired angle. It is also contemplated that the

sidewalls

54 and 56 may not taper toward one another.

The distal end portion 16 may include a plurality of projections or standoffs 60 (fig. 1) extending from a distal portion of the distal end portion 16. The projection 60 has the same general V-shape as the projection 40 and is smaller than the projection 40. The tab 60 has a first side 62 and a second side 64, the first side 62 and the second side 64 having a smaller length than the first side 42 and the second side 44 of the tab 40.

The projections or

uprights

40, 60 are arranged in circumferentially extending rows (fig. 1). It is contemplated that each row has six

projections

40, 60. It is contemplated that each of the rows may have any desired number of

tabs

40 or 60. Each of the

projections

40, 60 is circumferentially offset relative to the projections on an adjacent row. The ribs 66 extend circumferentially between

adjacent projections

40, 60 in each row. The rib 66 extends between the ends of the

side walls

54, 56 opposite the intersection 48.

The catheter 20 may have a stylet 100 (fig. 8), which stylet 100 provides rigidity to the catheter 20 so that a physician or operator may place the collection portion 12 in the back of the throat of the subject for easier swallowing. The stylet 100 may extend through the catheter 20 from the first or proximal axial end portion 14 of the adjacent collection portion 12 to the connector 102. The connector 102 is connected with the catheter 20 and allows introduction of fluid into the catheter for expanding the distal end portion 16 of the collecting section 12. The stylet 100 is preferably made of a Polyetheretherketone (PEEK) polymer. However, the stylet may be a stainless steel guidewire, a polymer monofilament extrusion, and/or a stainless steel monofilament core. The stylet 100 may have a rounded flexible distal end 104 spaced from the collecting portion 12 (see fig. 3). The flexible distal end 104 may be a graduated sharpened tip for added flexibility. The distal end 104 may be the most flexible portion of the stylet 100.

The proximal end 106 (fig. 8-9) of the catheter 20 is connected to the connector 102. The connector 102 may be a Y-shaped fitting having a first branch 110 connected to the proximal end 106 of the stylet 100. The proximal end 106 of the stylet 100 extends through the first branch 110 into a cap 112 that seals and encloses the first branch. The proximal end 106 is connected to the cap 112 and the first leg 110 with epoxy and is cut off flush with the proximal end of the cap 112. An epoxy may connect the cap 112 to the first branch 110. It is envisaged that the stylet 100 may be fixedly connected to the cap 112, such as by insert moulding. The stylet 100 may then be inserted into the Y-fitting 102 and catheter 20 and connected to the Y-fitting by a cap. The stylet 100 can then be removed from the catheter 20 and the Y-fitting 102, if desired. The catheter 20 may be lubricated to allow removal of the stylet 100 from the catheter. It is also contemplated that the proximal end 106 may extend through a Tuohy-Borst adapter connected to the first branch 110 to allow the user to unfasten the Tuohy-Borst adapter and remove the stylet 100, thereby reducing the stiffness of the catheter 20. It is also contemplated that the stylet may extend along the outside of the catheter 20.

The Y-shaped fitting 102 has a second branch 120 extending at an angle relative to the first branch 110. The second branch 120 may have a stopcock valve 122 for opening and closing the second branch. A syringe may be connected to the second branch 120 for introducing a fluid, such as air, into the Y-fitting 102 and the conduit 20 to expand the distal end portion 16 of the collection portion 12 and apply a vacuum to remove the fluid after collection of the sample to collapse the distal end portion 16. Stopcock 122 may be used to retain fluid in conduit 20 and collection portion 12 while taking a sample. Stopcock 122 and the syringe help control the injection of fluid to move distal end portion 16 between the collapsed and expanded positions.

The disc 126 may be connected to the proximal end of the catheter 20 or the distal end of the connector 102. The disc 126 extends radially away from the catheter 20 to prevent insertion of the connector 102 into the mouth and/or throat of a subject.

With the distal end portion 16 in the collapsed or contracted position, the collecting portion 12 is moved to a collecting site within a body cavity, such as the esophagus. The collecting portion 12 may be swallowed by the subject. The stylet 100 can be manipulated to place the collection portion 12 into the back of the throat of the subject to assist in swallowing the collection portion. It is also contemplated that the subject may be cannulated with the collection portion 12 attached to the catheter. The distal end portion 16 may be held in the collapsed or retracted position by applying a vacuum to the collection portion 12 through the support member 20. The support member 20 or catheter may have depth markings to determine a collection site within the subject's anatomy. The collecting portion 12 can be moved past the Lower Esophageal Sphincter (LES) and pulled in a proximal direction towards the LES. When the collecting portion 12 engages the LES, the operator or physician may sense the increased tension in the catheter 20. The distal end portion 16 of the collecting portion 12 may expand when LES is sensed. When the collecting portion 12 is at or near the collection site, the distal end portion 16 moves from the collapsed position to the expanded position. A syringe connected to the Y-fitting 102 may be activated to apply a pressurized fluid, such as air, to the distal end portion 16 to axially move the distal end portion from the collapsed position to the expanded position.

When the distal end portion 16 is in the expanded position, the collection portion 12 moves within the esophagus or body lumen to collect a biological sample, such as tissue, cells, proteins, RNA, and/or DNA, from a collection site. It is contemplated that the collection portion 12 is moved in a proximal direction only such that the expanded distal end portion 16 engages a collection site to collect the biological sample. Depth markings on the support member 20 or catheter may be used as a guide. For example, the catheter may have markings on its length that begin at 20cm of the proximal end of the balloon and extend to 60cm in 5cm increments. After collection of the biological sample, the distal end portion 16 is moved from the expanded position to the collapsed or retracted position. The distal end portion 16 may be moved from the expanded position to the collapsed position by applying a vacuum to the collection portion 12 using a syringe connected to the Y-shaped fitting 102. When the collection portion 12 is moved out of the body cavity, the distal end portion 16 does not engage the body cavity and prevents the collected biological sample from being contaminated by tissue from areas along the body cavity other than the collection site. Once the collection device 10 is removed from the subject, the biological sample is collected via the impactor, and/or the collection portion 12 or distal end portion 16 may be cut from the support member 20 and placed in a biological sample vial.

Another embodiment of a collection device 140 is shown in fig. 10. The collection device 140 is generally similar to the collection device shown in fig. 1-9 and has a collection portion 142, the collection portion 142 having a first or proximal end portion 144 and a second or distal end portion 146. The distal axial end portion 146 can expand and contract. The first or proximal axial end portion 144 is relatively rigid. Thus, the proximal end portion 144 has a fixed radial extent. The second or distal end portion 146 of the collecting portion 142 has an expanded or expanded position similar to the expanded position shown in fig. 1, and a collapsed or contracted position shown in fig. 10. The distal end portion 146 has a convex shape when in the expanded or expanded position. The distal end portion 146 extends into the first or proximal axial end portion 144 when in the collapsed or retracted position and has a concave shape. The distal end portion 146 may be retracted when in the collapsed position. The distal end portion 146 extends axially into the interior of the proximal end portion 144 when in the collapsed or retracted position. Thus, the distal end portion 146 moves axially or longitudinally relative to the proximal end portion 144 when moving between the collapsed position and the expanded position.

A reinforcing sleeve 148 is connected to the proximal end portion 144. Sleeve 148 may be axially inserted into proximal end portion 144 of collecting portion 142 such that distal end portion 146 extends into the sleeve when the distal end portion is in the collapsed position. The sleeve 148 is retained in the proximal end portion 144 by a distal undercut edge 150 on the proximal end portion. Sleeve 148 may be axially inserted into proximal end portion 144 until undercut edge 150 snaps over the sleeve to retain the sleeve in the proximal end portion. The undercut edge prevents the sleeve 148 from being able to slide out into the distal end portion 146. Sleeve 148 may be a polypropylene molded cylinder that provides additional column strength to proximal end portion 144 to help prevent the column and sidewalls from telescoping during vacuum retraction of distal end portion 146. The sleeve 148 allows for a thinner wall of the proximal end portion 144. The thinner walls of the proximal end portion 144 provide more space inside the proximal end portion to make the distal end portion 146 easier to retract. The ease of retraction of distal end portion 146 may enhance the ability to collect as much biological sample as possible. If there is too much friction between the surfaces of the distal end portion 146 as the distal end portion retracts into the proximal end portion 144, the sample may be scraped off. Sleeve 148 enhances the reliability of retraction and reduces the friction of the surfaces of distal end portion 146 against each other during retraction. The sleeve 148 may be a polymer and/or metal thin-walled sleeve inserted or insert molded into the proximal end portion 144. Sleeve 148 provides hoop strength and helps prevent proximal end portion 144 from telescoping under vacuum.

The distal end portion 146 has an outer surface for collecting tissue when the distal end portion is in the expanded position. The outer surface faces radially outward when the distal end portion 146 is in the expanded position, and may face radially inward when the distal end portion is in the collapsed or retracted position. The outer surface of distal end portion 146 may have a plurality of protrusions or standoffs 152 for collecting tissue. The protrusion 152 may have a V-shape similar to the V-shaped protrusion 40 illustrated in fig. 1-7.

Another embodiment of a collection device 160 is illustrated in fig. 11. The collection device 160 is substantially similar to the collection device shown in fig. 1-9, however, the collection device 160 illustrated in fig. 11 has a double V-texture. The collection device 160 has a collection portion 162, the collection portion 162 having a first or proximal end portion 164 and a second or distal end portion 166. The distal axial end portion 166 may expand or contract. The first or proximal axial end portion 164 is relatively rigid. Thus, the proximal end portion 164 has a fixed radial extent. The second or distal end portion 166 of the collecting portion 162 has an expanded or expanded position similar to the expanded position shown in fig. 1 and a collapsed or contracted position similar to the collapsed position shown in fig. 3. The collecting portion 162 is shown in fig. 11 in a non-expanded position between an expanded position and a collapsed position. The distal end portion 166 has a convex shape when in the expanded or expanded position. The distal end portion 166 extends into the first or proximal axial end portion 164 and has a concave shape when in the collapsed or retracted position. The distal end portion 166 extends axially into the interior of the proximal end portion 164 when in the collapsed or retracted position. Thus, the distal end portion 166 moves axially or longitudinally relative to the proximal end portion 164 when moving between the retracted position and the expanded position.

The distal end portion 166 has an outer surface for collecting tissue when the distal end portion is in the expanded position. The outer surface faces radially outward when the distal end portion 166 is in the expanded position, and may face radially inward when the distal end portion is in the collapsed or retracted position. The outer surface of the distal end portion 166 may have a plurality of projections or standoffs 172 for collecting tissue. The protrusion 172 may form a double V shape. Each of the projections 172 is similar to the V-shaped projection 40 illustrated in fig. 1-7. Each V-shaped projection 172 is directly connected to an adjacent V-shaped projection.

Another embodiment of a collection device 180 is illustrated in fig. 12. The collection device 180 is generally similar to the collection device shown in fig. 1-9 and has a collection portion 182, the collection portion 182 having a first or proximal end portion 184 and a second or distal end portion 186. The distal axial end portion 186 can expand and contract. The first or proximal axial end portion 184 is relatively rigid. Thus, the proximal end portion 184 has a fixed radial extent. The second or distal end portion 186 of the collecting portion 182 has an expanded or expanded position similar to the expanded position shown in fig. 1, and a collapsed or contracted position shown in fig. 12. The distal end portion 186 has a convex shape when in the expanded or expanded position. The distal end portion 186 extends into the first or proximal axial end portion 184 when in the collapsed or retracted position and has a concave shape. The distal end portion 186 may be retracted when in the collapsed position. The distal end portion 186 extends axially into the interior of the proximal end portion 184 when in the collapsed or retracted position. Thus, the distal end portion 186 moves axially or longitudinally relative to the proximal end portion 184 when moving between the retracted position and the expanded position.

The distal end portion 186 has an outer surface for collecting tissue when the distal end portion is in the expanded position. The outer surface faces radially outward when the distal end portion 186 is in the expanded position, and may face radially inward when the distal end portion is in the collapsed or retracted position. The outer surface of the distal end portion 186 may have a plurality of projections or standoffs 192 for collecting tissue. The protrusion 192 may have a V-shape similar to the V-shaped protrusion 40 illustrated in fig. 1-7.

The collection device 180 includes a gel cap or gelatin cover or cap 194 that can be loaded over the end of the collection portion 182. The cap 194 retains the distal end portion 186 in the collapsed position during insertion and movement of the collection portion 182 to the collection site. When the collection portion 182 reaches the body cavity, the cap 194 drops, pops off, and/or dissolves. The cap 194 may be dislodged in response to movement of the distal end portion 186 from the collapsed position to the expanded position.

Another embodiment of a collection device 200 is illustrated in fig. 13. The collection device 200 is generally similar to the collection device shown in fig. 1-9 and has a collection portion 202, the collection portion 202 having a first or proximal end portion 204 and a second or distal end portion 206. The distal axial end portion 206 may expand and contract. The first or proximal axial end portion 204 is relatively rigid. The second or distal end portion 206 of the collection portion 202 has an expanded or expanded position similar to the expanded position shown in fig. 1, and a collapsed or contracted position shown in fig. 13. The distal end portion 206 has a convex shape when in the expanded or expanded position. The distal end portion 206 extends into the first or proximal axial end portion 204 when in the collapsed or retracted position and has a concave shape. The distal end portion 206 may be retracted when in the collapsed position. The distal end portion 206 extends axially into the interior of the proximal end portion 204 when in the collapsed or retracted position. Thus, the distal end portion 206 moves axially or longitudinally relative to the proximal end portion 204 when moving between the collapsed position and the expanded position.

The distal end portion 206 has an outer surface for collecting tissue when the distal end portion is in the expanded position. The outer surface faces radially outward when the distal end portion 206 is in the expanded position, and may face radially inward when the distal end portion is in the collapsed or retracted position. The outer surface of the distal end portion 206 may have a plurality of protrusions or standoffs 212 for collecting tissue. The protrusion 212 may have a V-shape similar to the V-shaped protrusion 40 illustrated in fig. 1-7.

The collection device 200 includes a weight 214 connected to the proximal end portion 204. The weight 214 may assist in swallowing the collection portion 202. The weight member 214 may be made of tungsten and inserted into the proximal end portion 204. It is contemplated that the weight member 214 may be insert molded to the proximal end portion 204.

Collection devices

140, 160, 180, and 200 may be used with catheter 20, stylet 100, and/or connector 102 of fig. 8-9. It is also contemplated that the sleeve 148, cap 194, and/or weight 214 may be used with or separate from any of the collection devices.

In some embodiments, a device 300 for collecting a biological sample in a subject. The device 300 may include an expandable distal end portion 316 attached to the tubular support member 20. The expandable distal end portion 316 may be designed to expand from within the proximal end portion 314, the proximal end portion 314 being coupled to the tubular support member 20 or being part of the tubular support member 20. The expandable distal end portion 316 may be expanded to extend outwardly from the proximal end portion 314 and contracted to retract within the proximal end portion 314. In some embodiments, a surface on the expandable distal end portion 316 may be provided with a variable thickness to facilitate movement of the expandable distal end portion 316 between the expanded state and the collapsed and retracted states. The variable thickness of the expandable distal end portion 316 may be configured to facilitate any combination of expansion, contraction, and retraction of the expandable distal end portion 316 relative to the proximal end portion 314. The variable thickness may also affect the shape and flexibility/rigidity of the expandable distal end portion 316 in any combination of expanded, contracted, and retracted states. In some embodiments, the surface of the expandable distal end portion 316 may include a plurality of protrusions or standoffs 312 positioned thereon to allow collection of a biological sample when the expandable distal end portion 316 is in the expanded state. The protrusions or standoffs 321 positioned on the expandable distal end portion 316 may also be accompanied by structures (e.g., ridges, valleys, etc.) formed by the variable thickness of the expandable distal end portion. The structure created by the variable thickness of the surface may also assist in trapping cells and transitioning between states of the expandable distal end portion 316.

Referring to fig. 14, in some embodiments, the collection device 310 may be designed for structured retraction of the distal end portion 316 into the proximal end portion 314, similar to as discussed with respect to

collection devices

140, 160, 180, and 200. Fig. 14 shows an example illustration of the distal end portion 316 expanded and at least partially expanded from the proximal end portion 314. To facilitate more predictable and consistent contraction and retraction of distal end portion 316 into proximal end portion 314, the structure of distal end portion 316 may be sized, shaped, constructed from a combination of materials, using a combination of stiffness, or a combination thereof, such that predictable contraction and retraction of distal end portion 316 is enabled. In some embodiments, the distal end 316a of the distal end portion 316 may be configured to be thinner in thickness and/or formed of a material that is thinner than the material of the proximal end 316b of the distal end portion 316. The thinner distal end 316a of the distal end portion 316 may be provided to facilitate improved retraction and retraction of the distal end portion 316.

With continued reference to fig. 14, the configuration of the distal end portion 316 may have a variable level of stiffness to facilitate controlled contraction and retraction into the proximal end portion 314. In some embodiments, the distal end 316a of the distal end portion 316 may be constructed of a lower durometer material than the proximal end 316b of the distal end portion 316. The lower hardness of the distal end 316a of the distal end portion 316 may be provided to facilitate improved retraction and retraction of the distal end portion 316. For example, the distal end 316a of the distal end portion 316 may be a silicone material having a hardness between approximately 20 shore a and 30 shore a, and the proximal end 316b may be a silicone material having a hardness between approximately 40 shore a and 50 shore a.

In some embodiments, the distal end portion 316 may include any combination of different stiffness levels at different locations to improve any of expansion, biological cell collection, contraction, and retraction to the proximal end portion 314. For example, the hardness level of the material of the distal end portion 316 may decrease from the proximal end 316b having the highest hardness level to the distal end 316a, with the distal end 316a having the lowest hardness level. In another example, the hardness level at an intermediate portion between the proximal end 316b and the distal end 316a may be a minimum hardness level.

Referring to fig. 15, in some embodiments, the distal end portion 316 may be designed to telescope in a layered, stackable, and/or compressible structure. For example, as depicted in fig. 15, the distal end portion 316 may have a plurality of collapsible folds forming an accordion or similar design to facilitate collapsing and retraction into the proximal end portion 314. Fig. 15 shows an example illustration of the distal end portion 316 expanded and at least partially expanded from the proximal end portion 314. In addition to the shape, each of the collapsible sections may have a different level of stiffness to ensure uniform compression. The collapsible sections may be formed using any combination of methods. For example, the distal end portion 316 may be formed entirely using a die, or using a combination of steps, such as using a die and then forming the fold as a second process using a heated die. In some embodiments, the accordion design may include a combination of different materials for the inner and outer folds to maintain the shape of the distal end portion 316 and the expansion, contraction, and retraction of the distal end portion 316.

Referring to fig. 16 and 17, in some embodiments, the distal end portion 316 may be designed to include additional structure for providing different stiffness of the distal end portion 316. Fig. 16 and 17 show example illustrations of the distal end portion 316 expanded and distended and at least partially expanded from the proximal end portion 314. Additional structure may include the tabs or upstands 312 discussed with respect to the tabs or

upstands

40, 60, 152, 212, as well as additional structural features. For example, as depicted in fig. 16, the distal end portion 316 may include a plurality of ridges 318 between the protrusions or standoffs 312 (e.g., chevron shape) on the surface of the distal end portion 316. The plurality of ridges 318 may be configured to change the expanded size and shape of the distal end portion 316. The ridge 318 may also be designed to assist the protrusion or riser 312 in collecting a biological sample. For example, the ridges 318 may be sized and shaped such that they are capable of capturing the target biological material.

In some embodiments, as depicted in fig. 17, ridges 318 may be provided as structural features as well as the primary cell collection element of distal end portion 316. The ridge 318 may be formed of any combination of materials, in any combination of shapes and sizes, in any combination of any stiffness. In some embodiments, the ridge 318 may be formed from the same material as the distal end portion 316, either as part of the same molding process used to manufacture the distal end portion 316 or as a separate process formed on the surface of the distal end portion 316. In some embodiments, the ridge 318 may have a rectangular cross-section made of the same material (e.g., silicone) as the rest of the distal end portion 316. The ridges may also be other shapes such as semi-circular, triangular, or any combination of polygonal or other shapes.

Referring to fig. 18, in some embodiments, the distal end portion 316 may be designed to include additional structure for providing different stiffness of the distal end portion 316. For example, the distal end portion 316 may include a stretch 320 along the length of the protrusion or riser 312 to create variable stiffness. The stretcher 320 may be created from any combination of sizes, shapes, and/or materials, including the same material as the rest of the distal end portion 316 having a higher level of stiffness or a different material having a higher level of stiffness. For example, the stretch may be in the range of half a degree to several degrees.

Fig. 18 shows an example illustration of the distal end portion 316 expanded and at least partially expanded from the proximal end portion 314.

As will be appreciated by those skilled in the art, the collection device 300 and in particular the distal end portion 316 may be designed for specific expansion and expansion characteristics, including any combination of the designs discussed with respect to the contraction and retraction designs discussed with respect to fig. 14-18.

In some embodiments, the distal end portion 316 is replaceably and removably connected to the proximal end portion 14. In other words, the distal end portion 316 may be removed from the proximal end portion 314 without the need to damage the distal end portion 316 (e.g., by cutting the proximal end portion 314). Distal end portion 316 may be removably coupled to proximal end portion 314 using any combination of methods and systems. For example, the distal end portion 316 may be threaded onto the proximal end portion 314 and/or the distal end portion 316 may be held on the proximal end portion 314 using a friction fit, an adhesive, or by a mechanical connection. Enabling the distal end portion 316 to be removed enables the remainder of the collection device 300, including the proximal end portion 314, to be cleaned and reused. Once removed, the distal end portion 316 may be packaged and/or sent for analysis of any collected biological sample. In some embodiments, the proximal end portion 314 can be removed from the catheter 20, and a combination of the retracted distal end portion 316 and the proximal end portion 314 can be provided for analysis. The proximal end portion 314 can be removed and replaced from the catheter 20 using any combination of methods, such as any combination of the methods discussed herein with respect to the removable and replaceable distal end portion 316.

Any combination of elements from fig. 1-18 may be combined to form a collection device according to the present disclosure. From the above description of the invention, those skilled in the art will perceive improvements, changes and modifications. Such improvements, changes and modifications are intended to be covered by the appended claims.

In operation, the

collection device

10, 160, 180, 200, 300 may be used to collect a biological sample within a subject's target location. For example, collection device 300 may be used to collect any combination of tissue, cells, proteins, RNA, and/or DNA in the esophagus of a subject. The collection device 300 may be provided as part of a kit that may be pre-assembled or otherwise required to be assembled prior to the biological sample collection process. For example, the kit may include a coiled catheter 20 coupled proximally to the connector 102 and distally to a removable and replaceable proximal end portion 314 and/or distal end portion 316. The kit may include any combination of the components discussed herein. In some embodiments, the kit may further include one or more syringes for controlling the expansion, contraction, and/or retraction of the distal end portion 316. The components of the kit may be inspected, assembled and prepared for use with a subject. For example, the proximal end portion 314 and/or the distal end portion 316 may be soaked in clean water to simulate and provide lubricity.

In some embodiments, one or more syringes may be sized/sized before the terminal to accurately perform various expansion, contraction and/or retraction steps. For example, a 10cc to 30cc syringe may be prepared for the collection device 300 by depressing the 10cc to 30cc syringe for connection to the stopcock plug 122, which the stopcock plug 122 pulls back the syringe to a 10cc to 15cc suction vacuum, which will fully retract the distal end portion 316 inside the proximal end portion 314. Thereafter, stopcock valve 212 can be closed to keep distal end portion 316 retracted inside proximal end portion 314 and the syringe can be removed.

Once the collection device 300 is ready, the subject may prepare the proximal end of the swallowing catheter 20, including the swallowing proximal end portion 314 and the distal end portion 316. For example, the subject may be sitting upright and/or a local anesthetic spray and/or lidocaine viscous may be applied to the pharynx to minimize the vomiting reflex. Thereafter, the proximal end portion 314 and the distal end portion 316 can be delivered to the back of the subject's mouth to be swallowed. When the subject swallows, it should be ensured that the length of the catheter 20 follows freely and does not restrict the distal end portion 316 from being swallowed down into the stomach of the subject. When the subject swallows the proximal end portion 314 and the distal end portion 316, the subject may drink a small amount of water. The subject may also be provided with a suitable local anesthetic spray and/or lidocaine mucoadhesive applied to the pharynx to minimize the vomiting reflex.

Once swallowed, peristaltic action helps to advance the catheter 20 and the proximal and

distal end portions

314, 316 to the desired location. In some embodiments, the catheter 20 may have markings to give an estimated location of the proximal end portion 314 and the distal end portion 316. For example, when the marker on the catheter shows 50cm at the dental arch, the proximal end portion 314 and the distal end portion 316 can be estimated to be located in the stomach. A 2cc to 12cc syringe (preferably 5 cc) connected to stopcock 212 can be used to deliver 2.6cc to 12.6cc of air through catheter 20 to proximal end section 314 and distal end section 316, 2.6 to 12.6cc of air being the amount of air delivered when the plunger is pulled all the way to the rear. Once proximal end portion 314 and distal end portion 316 are within the stomach, as judged by labeling or other confirmation methods, 2.6cc to 12.6cc (preferably 5.6 cc) of fluid (e.g., air, gas, liquid, etc.) may be injected from the syringe through catheter 20 to inflate and/or expand distal end portion 316. In some cases, portions of the distal end portion 316 may be confirmed using other methods, such as a stethoscope or using an imaging device. In some embodiments, the distal end portion 316, when in place, may expand to a diameter of 16mm to 18 mm. Thereafter, stopcock valve 212 may be closed and the 2cc to 12cc syringe may be removed.

In some embodiments, with distal end portion 316 expanded within the stomach, the physician may gently retract catheter 20 until moderate resistance is felt due to distal end portion 316 contacting the Lower Esophageal Sphincter (LES) at the gastro-esophageal junction (GEJ). Once the LES/GEJ are contacted by the distal end portion 316, the marking of the catheter 20 at the dental arch may be recorded. Based on the recorded markers, the physician may continue to pull the distal end portion 316 approximately 2cm to 15cm from the proximal position of the LES/GEJ to collect a sample from the distal portion of the esophagus (e.g., abnormal columnar epithelial cells that may indicate Barrett's Esophagus (BE)). As the distal end portion 316 passes through the LES/GEJ, there may be a greater level of resistance until the LES relaxes and the distal end portion 316 moves more freely. Once the distal end portion 316 passes through the LES/GEJ, the expansion of the catheter 20 may subside and then provide a more accurate measurement for a sample length of about 2cm to 15 cm.

In some embodiments, the subject may have an expanded GEJ that can be identified without the LES/GEJ being felt by the user despite the balloon being pulled all the way back 30cm above the dental arch. In this case, additional steps may be taken to help determine the location of the LES prior to sampling. Initially, stopcock valve 212 may be opened and a vacuum pulled (e.g., using a 5cc to 20cc syringe), and distal end portion 316 inverted into proximal end portion 314. Further, the stopcock valve 212 may be moved to the closed position and the proximal end portion 314 may be advanced into the subject's stomach again until the mark on the catheter 20 shows 50cm at the dental arch. Once in place, stopcock valve 212 may be opened and 11cc (e.g., air) may be inserted into catheter 20 to inflate distal end portion 316, and stopcock valve 212 may be closed to maintain the inflation within distal end portion 316. Thereafter, the catheter 20 may be pulled back gently until moderate resistance is felt, indicating that the distal end portion 316 is contacting the LES. This position may be recorded based on markers near the dental arch to indicate the location of the LES. With the location known, the distal end portion 316 can be withdrawn into the proximal end portion 314 (e.g., by applying a vacuum) and the normal steps can be performed with the known location of the LES. For example, a balloon inflation of about 2.6cc to 12.6cc (preferably 5.6 cc) is used and the position in cm from the arch is used for LES.

In some embodiments, once distal end portion 316 has moved the desired distance within the esophagus, distal end portion 316 may be retracted and retracted within proximal end portion 314 to protect any collected biological sample during withdrawal of device 200. For example, once distal end portion 316 is pulled past the sample site at the distal esophagus, stopcock valve 212 may be opened to collapse distal end portion 316. Once deflated, another syringe, e.g., 15cc to 25cc, may be connected to stopcock valve 212 to withdraw 5cc to 20cc of fluid from catheter 20, thereby retracting distal end portion 316, with the distal esophageal sample protected within proximal end portion 314. Stopcock valve 212 may then be closed and the 15cc to 25cc syringe removed.

With the sampling distal end portion 316 protected within the proximal end portion 314, the catheter 20 may be removed. By pulling back the catheter 20, the catheter 20 can be completely removed from the esophagus/mouth, including removing the proximal end portion 314 and the distal end portion 316. The proximal end portion 314 and the distal end portion 316 may feel that they are temporarily stuck at the upper esophageal sphincter and will require a forceful pull to withdraw the collection device 300 as a whole. In some embodiments, the physician may ask the subject to swallow while pulling the proximal end portion 314 and the distal end portion 316 through the upper esophageal sphincter for easier removal. This will relax the upper sphincter and make it easier to extract the proximal end portion 314 and the distal end portion 316.

In some embodiments, once removed, proximal end portion 314 and distal end portion 316 may be protected from contamination, for example, by placing proximal end portion 314 and/or distal end portion 316 within a sealable container (e.g., a vial, a sample bag, etc.). In some embodiments, the distal end portion 316 is removed from the proximal end portion 314. For example, a 2cc to 12cc syringe may be used to deliver 1cc to 5cc of fluid to inflate the distal end portion 316. The fluid should be delivered at a slow rate to ensure that the biological sample is not inadvertently pushed away from the distal end portion 316. Thereafter, the syringe should be removed and stopcock valve 212 held open to collapse distal end portion 316. The distal end portion 316 may be removed without contacting the surface of the distal end portion 316 and the collected sample. For example, the distal end portion 316 may be severed from the proximal end portion 314, the distal end portion 316 may be uncoupled (e.g., mechanically connected), unscrewed, removed from a friction fit, and the like. The removed distal end portion 316 may be inserted into any type of container for storage, transport, and/or future analysis. In some embodiments, in embodiments of the removable and replaceable distal end portion 316, the collection device 300 can be sterilized for future use and to receive a new distal end portion 316.

As will be appreciated by those of skill in the art, the numbers and devices provided herein are for exemplary purposes only. For example, although the use of different sized syringes is provided, any combination of mechanisms for increasing or removing pressure from the catheter 20 and the distal end portion 316 may be used without departing from the scope of the present invention. Similarly, the range or indicia may vary based on the subject, application, etc., without departing from the scope of the invention.

As used herein, the terms "comprises" and "comprising" are intended to be interpreted as inclusive, rather than exclusive. As used herein, the terms "exemplary," "example," and "illustrative" are intended to mean "serving as an example, instance, or illustration," and should not be construed as indicating or not indicating a preferred or advantageous configuration relative to other configurations. As used herein, the terms "about," "approximately," and "approximately" are intended to encompass variations that may exist in upper or lower limits within subjective or objective value ranges, such as variations in performance, parameters, size, and dimensions. In one non-limiting example, "about," "approximately," and "approximately" are expressed as 10 percent or plus 10 percent or less, or minus 10 percent or less. In one non-limiting example, the terms "about," "approximately," and "approximately" are meant to be close enough to be considered inclusive by a person of ordinary skill in the relevant art. As used herein, the term "substantially" refers to the complete or nearly complete extent or degree of an action, feature, property, state, structure, item, or result, as will be understood by those skilled in the art. For example, an object that is "substantially" circular would mean that the object is completely circular, or close to a circle as would be recognized or understood by one skilled in the art, within mathematically determinable limits. In some cases, the exact degree of allowable deviation from absolute completeness may depend on the particular context. In general, however, near-perfect will have the same overall effect as achieved or attained, both absolute and total. As one of ordinary skill in the art will appreciate, the use of "substantially" when used in a negative sense is equally applicable to refer to the complete or near complete absence of an action, feature, property, state, structure, item, or result.

Many modifications and alternative embodiments of the disclosure will be apparent to those skilled in the art in view of the foregoing description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the best mode for carrying out the disclosure. The details of the structure may be varied substantially without departing from the spirit of the disclosure, and the exclusive use of all modifications which come within the scope of the appended claims is reserved. Embodiments have been described in this application in a manner that enables a clear and concise application to be written, but it is intended and will be appreciated that the embodiments may be combined or separated in various ways without departing from the invention. It is intended that the disclosure be limited only to the extent required by the appended claims and the applicable rules of law.

It is also to be understood that the following claims are to cover all generic and specific features of the invention described herein, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween.

Claims

1. A device for collecting a biological sample from a subject, the device comprising:

an expandable portion attached to a tubular member and designed to expand from within the tubular member and retract into the tubular member when expanded;

a surface on the expandable portion, the surface being provided with a variable thickness to facilitate movement of the expandable portion between the expanded and retracted states; and

a plurality of protrusions on the surface that allow collection of the biological sample when the expanded portion is in the expanded state.

2. The device of claim 1, wherein the variable thickness is defined by a distal end of the expandable portion being thinner relative to a proximal end of the expandable portion.

3. The device of claim 1, wherein the variable thickness is defined by a collapsible fold positioned circumferentially around the surface of the expandable portion.

4. The device of claim 1, wherein the expandable portion comprises a plurality of different hardness levels to facilitate a combination of expansion, contraction, and retraction.

5. The apparatus of claim 1, wherein the expandable portion is removable from and replaceable on the tubular member using at least one of a friction fit or a mechanical fit.

6. The device of claim 1, wherein the variable thickness is defined by a ridge positioned circumferentially about the surface of the expandable portion.

7. The device of claim 6, wherein a plurality of the ridges are positioned between each row of the plurality of projections to vary the expanded size and shape of the expandable portion.

8. The device of claim 6, wherein the plurality of ridges facilitate collection of the biological sample.

9. The apparatus of claim 6, wherein the expandable portion comprises a stretch extending along a length of each row of the plurality of protrusions to create a variable stiffness of the expandable portion.

10. The device of claim 1, wherein the tubular member is a catheter coupled to the expandable portion at a proximal end and to a connector at a distal end.

11. The device of claim 10, wherein the connector is a Y-shaped fitting having a first leg extending at an angle to a second leg of the connector, the second leg including a stopcock.

12. The apparatus of claim 1, wherein the expandable portion has an outer surface facing radially outward when the expandable portion is in the expanded state and radially inward when the expandable portion is in the retracted position.

13. The device of claim 6, wherein a first sidewall of the tissue collection projection extends substantially perpendicular to an outer surface of the expandable portion when the expandable portion is in a non-expanded position between the retracted position and the expanded position, and a second sidewall of the tissue collection projection tapers toward the first sidewall as the sidewall extends radially outward from the outer surface.

14. The device of claim 13, wherein at least one of the plurality of protrusions has a V-shape, the first side wall facing in a proximal direction and forming an inner wall of the V-shape, and the second side wall facing in a distal direction and forming an outer wall of the V-shape.

15. The device of claim 1, wherein the expandable portion has a hardness between 20 shore a and 70 shore a.

16. The device of claim 1, further comprising a cap extending over the expandable portion when the expandable portion is in a retracted position to retain the expandable portion in the retracted position.

17. The apparatus of claim 1, wherein the expanded state is facilitated by the presence of positive pressure.

18. The apparatus of claim 1, wherein the retracted state is facilitated by the presence of negative pressure.