Patent Publication Number: US-2009240164-A1

Title: Device and Method for Collecting Tissue Samples

Description:
BACKGROUND 
     1. Field of the Invention 
     The present invention relates generally to medical sampling devices and in particular to a device and method for collecting tissue samples. 
     2. Description of Related Art 
     Within the medical industry there are a variety of devices for sampling tissue from various sites of the human body. Sampling of the endometrium has a long history of utilizing different samplers ranging from curettes and pipelles to various brushes and simple swabs. Historically, all of these devices have their limitations. For example, the curette can obtain a significant amount of tissue from the endometrium. However, it requires a surgical setting, anesthesia, and can cause possible permanent scarring of the endometrial lining which can lead to infertility. The pipelle technique involves aspiration of the tissues sample and can be done on an outpatient basis. However, diffuse sampling of the endometrium is limited. Different brushes are used and have limitations such as large size which makes tissue collection uncomfortable for the patient or brushes having the inability to exfoliate sufficient cells for examination or inability to capture the exfoliated cells, or there are not indicators on the depth of placement of the brush into the cavity, and/or brushes can cause contamination of the sample by other body sites such as the cervix and the vagina. Furthermore, there is no provision among known existing brushes for adjusting the brush to accommodate differing anatomy. 
     Because current technology provides a single brushhead length and limited bristle length, there is a compromise between patient comfort and collection effectiveness. Therefore, a need exists for an improved device and method for collecting tissue samples. 
     All references cited herein are incorporated by reference to the maximum extent allowable by law. To the extent a reference may not be fully incorporated herein, it is incorporated by reference for background purposes and indicative of the knowledge of one of ordinary skill in the art. 
     SUMMARY 
     The problems presented in existing tissue sampling devices are solved by the device and method of the present invention. In accordance with one embodiment a tissue sampling device is provided. The tissue sampling device includes a spirally twisted flexible wire with opposed proximal and distal ends. Also included is a plastic tube covering a significant portion of the wire to provide additional rigidity without making the overall brush stiff. Along the distal end portion of the wire is a brush that includes bristles that were used for collecting a tissue sample. The bristles are fixed within the spirally twisted wire near the distal end and are tapered from smaller to larger towards the distal end of the wire. Tapering of the bristles from the distal end of the device allows for more global tissue collection of the endometrium because of the shape of the endometrial cavity. An atraumatic bulb is located on the extreme distal end of the twisted wire. The atraumatic bulb aids in insertion into the cervical area without trauma and helps prevent further trauma to the uterus. The tissue sampling device also includes a handle on the extreme proximal end of the plastic core. 
     In accordance with another embodiment, the plastic tube and twisted wire are contained within a sheath of shorter length than the twisted wire, such that the sheath can be moved along the plastic tube to the atraumatic bulb on the distal end of the twisted wire, thereby covering the brush during insertion and removal after tissue collection. Before insertion, the sheath can be moved into position over the distal end of the twisted wire to protect the brush during insertion. Having the brush covered during insertion also increases comfort for the patient and protects the brush from collecting tissue from unintended areas. The sheath is moved back toward the proximal end of the twisted wire after the device has been inserted to the proper collection depth, exposing the brush and allowing for collection of a tissue sample. The sheath may be moved to completely uncover the brush or may be moved in gradients to uncover portions of the brush. This allows the practitioner to adjust the effective collection area of the brush based on the anatomy of the patient. The plastic tube covering the wire is scored in centimeter gradations along the plastic tube with markings indicating the exact length of the brush inserted into the uterus, starting from the distal tip of the brush to the proximal end of the plastic tube. This allows the clinician to know how deeply the brush is inserted into the uterus. The sheath is approximately the same length as the plastic tube and in position to cover the brush bristles prior to insertion. The sheath may be formed of a clear material such that the gradations on the plastic tube may be viewed through the sheath. The ability to measure insertion depth increases the certainty that the tissue sample collected is from the correct area, After a tissue sample is collected from the proper area, while the tissue sampling device remains inserted, the sheath can be moved back along the distal end of the twisted wire to cover the brush bristles before removing the brush. This allows for the tissue sample to be protected on the brush within the sheath during removal. 
     Additionally, the gradations along the flexible tube allow the practitioner to measure the length of bristles exposed. As the practitioner pulls the sheath from its insertion position towards the handle, the further the sheath is pulled the more bristles are exposed. The gradations (ruler) provide a visual confirmation of this measurement and allow the practitioner to be precise in exposing only a certain length of the brush bristles. This measurement allows the practitioner to have better control of where the tissue is sampled and allows the practitioner to adjust the length of brush based on patient specific parameters; such as uterine size measured during previous tests or inferred based on patient history. Control of brush exposure increases sampling precision and patient comfort. 
     Other objects, features, and advantages of the present invention will become apparent with reference to the drawings and detailed description that follow. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a perspective view of a tissue sampling device in accordance with an embodiment of the present invention; 
         FIG. 1B  is a close up of the distal end of the device in  FIG. 1A  with conically tapered brush bristles; 
         FIG. 1C  is a close up of the distal end of the device in  FIG. 1A  with step tapered brush bristles; 
         FIG. 2A  is a perspective view of a tissue sampling device in accordance with an embodiment with a sheath positioned to cover the brush bristles; 
         FIG. 2B  is a close up of the distal end of the device in  FIG. 2A  with conically tapered brush bristles enclosed within the sheath; 
         FIG. 2C  is a close up of the distal end of the device in  FIG. 2A  with step tapered brush bristles enclosed within the sheath; 
         FIG. 3A  is a perspective view of a tissue sampling device in accordance with an embodiment with the sheath partially pulled back from the brush bristles; 
         FIG. 3B  is a close up of the distal end of the device in  FIG. 3A  with conically tapered brush bristles; 
         FIG. 3C  is a close up of the distal end of the device in  FIG. 3A  with step tapered brush bristles; 
         FIG. 4A  is a perspective view of a tissue sampling device in accordance with an embodiment with the sheath pulled all the way back to fully expose the brush bristles; 
         FIG. 4B  is a close up of the distal end of the device in  FIG. 4A  with conically tapered brush bristles; 
         FIG. 4C  is a close up of the distal end of the device in  FIG. 4A  with step tapered brush bristles; 
         FIG. 5  is a view of the tissue sampling device inserted within a uterus with the brush totally covered by the sheath; 
         FIG. 6  is a view of the tissue sampling device inserted within a uterus with the brush partially exposed; 
         FIG. 7  is a view of the tissue sampling device inserted within a uterus with the brush fully exposed. 
     
    
    
     DETAILED DESCRIPTION 
     All references cited herein are incorporated by reference to the maximum extent allowable by law. To the extent a reference may not be fully incorporated herein, it is incorporated by reference for background purposes and indicative of the knowledge of one of ordinary skill in the art. 
     In the following detailed description of the preferred embodiments, reference is made to the accompanying drawings, which form a part hereof, and in which is shown by way of illustration specific preferred embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is understood that other embodiments may be utilized and that logical mechanical changes may be made without departing from the spirit or scope of the invention. To avoid detail not necessary to enable those skilled in the art to practice the invention, the description may omit certain information known to those skilled in the art. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined only by the appended claims. 
     Referring to  FIG. 1 ,  FIG. 1A  is a perspective view of a tissue sampling device  10  in accordance with an embodiment of the present invention,  FIG. 1B  is a close up of the distal of the device  10  in  FIG. 1A  with conically tapered brush bristles  22 , and  FIG. 1C  is a close up of the distal of the device  10  in  FIG. 1A  with step tapered brush bristles  22 . A similar format is used in subsequent figures for consistency. 
     The distal end  14  of the tissue sampling device  10  shows twisted wire  18  extending from the plastic tube  12 . In accordance with one embodiment the tissue sampling device  10  is used for uterine endometrial tissue collection. The tissue sampling device of the present embodiment includes an elongated twisted wire  18  having an opposed proximal end  16  and distal end  14 . The length of the wire  18  in the present embodiment is approximately 28.5 cm, which has been found to be a functional length for the present application. However, one skilled in the art will understand that a wire  18  of different length may be used for different applications. The wire  18  should not be too rigid as to cause discomfort for the patient, but also cannot be so flimsy that proper insertion is made difficult. One skilled in the art will understand that the wire  18  can be made from a variety of flexible materials, such as stainless steel, and the like. 
     The twisted wire  18  is comprised of a single elongated wire that is contained within the tube  12 . The wire  18  is spirally wrapped at its half-length such that the wire is folded over and the two half lengths are twisted together to form its final length. The wire  18  should be made of stainless steel to protect the health of the patient. While one skilled in the art will understand that the diameter of the wire can vary and still obtain its usefulness, the diameter must be such that the wire  18  can be spirally wrapped at its half-length and enclosed within a tube  12  having an approximate diameter of 3 mm. The distal end  14  of the wire  18  includes a brush  20  approximately 5.5 cm in length along the distal end  14  of the wire  18 . The brush  20  includes bristles  22  fixed within the spirally wrapped wire  18  that protrude beyond the wire  18 . The bristles  22  can be made from most materials that are used for current brush tissue sampling systems, such as nylon and other FDA approved materials for such devices. 
     The tissue sampling device  10  includes an atraumatic bulb  24  located on the distal end  14  of the wire  18 . The bulb can be made from any biocompatible material, such as a flexible plastic, that will protect the surrounding tissue during collection. The device  10  also includes a handle  26  on the proximal end  16  of the wire  18 . Any of a variety of handles can be used with the device. For example, a ring can be used which may help with removing the device after collection. As shown, handle  26  is a hexagonal cylinder, which may assist with rotating the device during tissue collection. In production, the twisted wire  18  and tube  12  are firmly attached to the handle  26  and may extend into the handle  26  to facilitate a firm connection. 
     Additionally, the plastic tube  12  may be scored or printed with centimeter gradations  30 , such as every centimeter from the distal end  14  of the plastic tube  12  to the proximal end  16  of the plastic tube  12 . In an embodiment, the gradations are numbered to show the distance from the distal tip of the device  10 . An additional sheath mark  32  may be added among the gradations as is discussed in more detail below. The gradations  30  allows for insertion depth measurement and brush exposure measurement to ensure accurate tissue sampling in a variety of anatomies. 
     As shown more clearly  FIGS. 1B and 1C , the diameter of the bristles  22  about the distal end  14  of the wire  18  may be tapered smoothly or in a step fashion, respectively. It has been found that the conically tapered brush bristles  22  may be easier to manufacture in some systems, but a step tapered brush bristles  22  pattern may be desired by some practitioners to give more certainty on the length of bristles  22  exposed during partial exposure of the bristles  22  as described with reference to  FIG. 3 . 
     In the tapered pattern of  FIG. 1B , the bristles  22  extend approximately 2 mm to 4 mm from the wire  18  to give a brush diameter of approximately 4 mm to 8 mm. The bristles extend approximately 5 cm to 7 cm along the wire  18  to give the practitioner the option of exposing a long or short brush, as discussed below. While one skilled in the art will understand that varying the brush length in small increments will not cause a discernible loss of functionality, a brush of this length has been found to have advantages over shorter brushes, especially when included with tapered bristles, such as more accurate tissue collection. 
     The stepped embodiment of  FIG. 1  C includes bristles  22  that begin approximately 5 mm from the atraumatic bulb  24  on distal end  14  of wire  18 . The bristles  22  have a length that forms a brush  20  first diameter of approximately 8 mm and cover approximately 2 cm of the distal end  14  of the wire  18 , then step down to bristles  22  having a length that forms a brush  20  second diameter of approximately 7 mm that cover the next approximately 2 cm of the distal end  14  of the wire  18 , and finally step down to bristles  22  having a length that forms a brush  20  third diameter of approximately 6 mm that cover the next approximately 2 cm of the distal end  14  of the wire  18 . These dimensions are provided as an embodiment only and may be adjusted to include more or less steps to provide the desired brush shape. 
     Turning now to  FIG. 2 ,  FIG. 2A  is a perspective view of a tissue sampling device with a sheath  28  positioned to cover the brush bristles,  FIG. 2B  is a close up of the distal of the device in  FIG. 2A  with conically tapered brush bristles,  FIG. 2C  is a close up of the distal of the device in  FIG. 2A  with step tapered brush bristles. In accordance with this embodiment, the tissue sampling device  10  includes a movable sheath  28  of shorter length than the wire  18  that slides over the tube  12  to allow for selective covering of the bristles  22 . The sheath  28  in the present embodiment is approximately 21 cm in length. While the sheath  28  may be of differing lengths without losing its functionality, the sheath  28  should be shorter than the wire  18  by the length of the brush  20 . The sheath  28  can be moved laterally either towards the distal end  14  or proximal end  16  of the wire  18 . When moved toward the distal end  14  of the wire  18 , the sheath  28  covers the brush  20 . Therefore, before inserting the tissue sampling device  10  for collection, the sheath  28  can be moved to the distal end  14  of the wire  18  to protect the brush  20  from errant tissue contamination during insertion. 
     When the sheath  28  covers the brush  20  during insertion, the bristles  22  of the brush  20  are pressed against the steel wire  18  in the distal end  14  direction, providing a small diameter insertion device which improves comfort for the patient. While covered during insertion, the bristles  22  are also protected fiom collecting tissue from unwanted areas, reducing the risk of misleading results. After the device  10  has been inserted to a proper depth for tissue collection, the sheath  28  can be moved in the proximal end  16  direction to expose the bristles  22  of the brush  20  for proper tissue collection, as shown in  FIGS. 3 and 4 . Once tissue collection is complete, the sheath  28  can be moved back to the distal end  14  of the tube  12  so that the bristles  22  and associated tissue sample are protected upon removal. The sheath  28  should have an inside diameter just larger than the outside diameter of the tube  12  so that movement of the sheath  28  along tube  12  can be made with ease. Similar to the tube  12 , the sheath  28  should be made of a material that is rigid enough to keep its shape during insertion of the device  10  and during the opening and closing of the sheath  28  during tissue collection. However, it should be flexible so as not to cause discomfort for the patient. In contrast to tube  12 , it is desirable for sheath  28  to be clear, allowing the practitioner to see any markings on tube  12  while tube  12  is covered by sheath  28 . One skilled in the art will understand that the sheath  28  can be made of plastic, other polymers approved by the FDA for such uses, and the like. 
     Another reason to have a transparent sheath  28  is to adjust the exposure of brush  20  during use as described below. In addition to gradations  30 , a sheath mark  32  may be added along tube  12  to indicate the proximal end of sheath  28  when brush  20  is fully covered. As sheath  28  is moved in a proximal end  16  direction, the amount of brush uncovered may be determined by reference to the distance between the proximal end  16  of the sheath  28  and the sheath mark  32 . Combining the sheath mark  32 , transparent sheath  28 , and a longer brush  20  with a wide range of bristles  22  lengths allows the practioner to use a single brush on a wide variety of anatomies without compromising either patient comfort or collection effectiveness. In particular, the uterus  34  has a generally conical shape, although the size will vary from patient to patient. The tapered brush  20  is longer in the area of the uterus  34  where a longer brush is easily tolerated by the patient and shorter where a longer brush would be uncomfortable and sample unwanted areas. 
     Referring now to  FIGS. 3 and 4 ,  FIG. 3  shows an embodiment with a portion of the brush  20  exposed, while  FIG. 4  shows the entire brush  20  exposed. In particular,  FIG. 3A  is a perspective view of a tissue sampling device  10  with the sheath  28  partially pulled back from the brush bristles  22 ,  FIG. 3B  is a close up of the distal end  14  of the device  10  in  FIG. 3A  with conically tapered brush bristles  22 ,  FIG. 3C  is a close up of the distal end  14  of the device  10  in  FIG. 3A  with step tapered brush bristles  22 . In contrast,  FIG. 4A  is a perspective view of a tissue sampling device  10  with the sheath  28  pulled all the way back to fully expose the brush bristles  22 ,  FIG. 4B  is a close up of the distal end  14  of the device  10  in  FIG. 4A  with conically tapered brush bristles  22 ,  FIG. 4C  is a close up of the distal end  14  of the device  10  in  FIG. 4A  with step tapered brush bristles  22 . The contrast between  FIG. 3  and  FIG. 4  shows that a range of brush  20  may be exposed to accommodate differing patient anatomy or differing sample goals as discussed further below. 
     In accordance with one method, a tissue sampling device  10  is provided having an elongated plastic tube  12  covering a portion of a spirally twisted wire  18  having opposed proximal  16  and distal  14  ends, wherein the plastic tube  12  is marked in gradations  30  along the length of the plastic tube  12 . The distal end  14  of the plastic wire  18  contains a brush  20  approximately 5 cm to 7 cm along the distal end  14  of the tube  12  and ending approximately one-half cm from the distal end  14  of the tube  12 . The brush  20  includes bristles  22  fixed within the spirally wrapped wire  18  about the diameter of the distal end  14  of the wire  18  protruding beyond the plastic tube  12  for collection of a tissue sample. The diameter of the bristles  22  about the distal end  14  of the wire  18  is approximately 6 to 8 mm and the bristles  22  are tapered from the distal end  14  of the wire  18 , in either a smooth or stepped fashion. The device  10  also including an atraumatic bulb  24  on the distal end  14  of the wire  18  and the proximal end  16  of the wire  18  includes a handle  26 . A movable sheath  28  of shorter length than the wire  18  is enclosed around the tube  12 . 
     Before insertion, the sheath  28  is moved along the tube  12  to the distal end  14  of the wire  18  to abut the atraumatic bulb  24  thereby covering the bristles  22  of brush  20 . Because the bristles  22  of the brush  20  extend in a radial direction, the bristles  22  lay against the wire  18  during insertion and removal to protect the bristles  22  from damage, and also protect the sample collected on the bristles  22 . This improves comfort for the patient and protects the brush  20  upon insertion and removal. The distal end  14  of the device  10  is then inserted into an area of tissue where a sample is to be taken, such as uterus  34  as shown in  FIG. 5 . Using the gradations  30  along the tube  12 , the insertion depth is measured to assure accurate placement of brush  20  within uterus  34 . The sheath  28  is then moved in the proximal end  16  direction to expose at least a portion of the brush  20  as shown in  FIG. 6 . In particular,  FIG. 6  depicts a uterus  34  of relatively smaller size and shows how partial exposure of a tapered brush  20  protects the comfort of the patient and accurate sampling. The length of brush  20  exposed is determined by the distance sheath  28  is pulled in a proximal end  16  direction. In a larger uterus  34 , more of the brush  20  may be exposed, or even the entire brush as shown in  FIG. 7 . The amount of brush being exposed may be determined by reference to the distance between the proximal end of the sheath  28  and the sheath mark  32 . The device  10  is then rotated using the handle  26  to collect a tissue sample. Before removing the device  10 , the sheath  28  is once again moved in the distal end  14  direction to the bulb  24  located on the distal end  14  of the wire  12 , such that the proximal end  16  of the sheath  28  aligns with the sheath mark  32 . This enables protection of the sample upon removal of the device  10 . The device  10  is then removed from the subject, and the tissue sample is collected from the brush  20 . 
     Even though many of the examples discussed herein are applications of the present devices and methods as used for collecting endometrial cells, the present devices and methods also can be applied for collecting tissue samples in other areas of the body or from non-human patients.