This disclosure relates generally to the collection of cell clusters for later use in examining the cell clusters. More specifically, this disclosure relates to a collector that is designed to enhance the capability of the collector to pick-up clusters or clumps of cells, for example from a cervix, and where the clusters of cells are collected in a manner where the spatial arrangement of the collected clusters of cells is preserved.
It is often necessary to collect various cell samples from patients for the purposes of screening for, detecting, and ultimate treatment of, a number of diseases and abnormalities. One of the major reasons for the collection of cellular samples is for the purpose of screening patients for cancer. For example, urine, sputum, breast nipple and fine needle aspirates, and exfoliated cells of the uterine cervix are screened by cytotechnicians and pathologists for the presence of abnormal cells suggestive of the presence of a solid tumor. When such suspicious cells are found, a more definitive diagnosis is reached by removing a sample of the tissue where a lesion is suspected, and submitting the sample for review by a pathologist.
It is generally accepted that diagnosis of cancer at its earliest stages affords the greatest opportunity for effective treatment. A corollary to this is that early diagnosis of a solid tumor corresponds to recognition of localized abnormalities, which at the cellular level are not that different from the surrounding tissue. This presents a challenge for screening of cellular samples where all context and comparison to neighboring cells is lost. One approach to this problem is to concentrate upon elements, i.e. groups of cells, which more closely approximate intact tissue elements. In fact, the presence of such clusters of cells, in and of itself, can be considered to be suggestive of a pre-cancerous or cancerous condition. However, it is also the case that normal tissue elements can be represented as cell clusters in samples collected for cytologic analysis.
Conventional sampling methods utilized in current screening procedures are capable of acquiring cells from a lesion, but then often disperse these cells into a typically much larger number of normal cells obtained from outside of the boundaries of the lesion. This dispersion results in the evaluation of a sample being an exercise in the detection of a rare event; that is, finding one or a few abnormal cells within a background consisting of a very large number (e.g. 50,000-300,000) of normal cells. Furthermore, and perhaps most significantly, dispersion eliminates the information that can be gained from determining the biological characteristics of small areas that might represent preneoplastic lesions. This essential information is present in the relationship among cells, and is not apparent by examining individual cells in isolation from adjacent cells within a tissue. Dispersion also precludes using the sample to determine the location of the lesion on the patient.
Therefore, it would also be desirable to provide improved cell collection procedures that facilitate the collection of cell clusters and which retain the spatial relationship that existed between cells prior to collection.
A cell collector and cell collection method are provided for collecting clusters of cells for subsequent analysis of the cells to screen for abnormalities. The cell collector is designed to enhance the capability of the collector to maintain the integrity of cellular clusters or clumps, and to facilitate transfer of the collected clusters of cells onto a receiving structure, for example a slide. In one embodiment, a combination of the material of the collector, the texture of the collection surface of the collector, and the use of expansion and rotation of the collector during collection facilitate the collection of the clusters of cells.
Preferably, clusters of cells are transferred from the collector to the receiving structure in such a way as to retain the spatial relationships that existed between the cells in the clusters prior to sampling. Orientation marks on the collector and the receiving structure assist in maintaining the spatial relationship during transfer.
The collector is expanded during collection as well as during transfer of the cells. Expansion during collection and transfer can occur through the use of air, by a mechanical expansion system, or through a combination of air and a mechanical system. Preferably, the collector can be expanded during transfer such that the cell clusters obtained from the endo- and ecto-cervical regions end up on a generally common plane for subsequent transfer to the receiving structure.
Cell cluster collection can be applied to a number of regions of the body, for example the cervix, the bladder, the lungs, the colon, and the ovaries. The clusters of cells can be collected from tissue, urine, induced sputum, cells washed from ovaries, and the like.
FIGS. 1A-C illustrate an example of cell collection from a uterine cervix.
FIGS. 5A-C are cross sectional views of the tip of the cell collector illustrating expansion of the cell collection tip during cell cluster collection.
FIGS. 6A-C illustrate the steps of cell cluster collection from a cervix using the cell collector.
FIGS. 7A-C illustrate a collector handle assembly that can rotate the cell collector during collection.
FIGS. 8A-B illustrate the tip of the cell collector prior to and after inflation, respectively, but prior to transfer, with colored marker simulating collected clusters of cells.
FIGS. 11A-C are detailed views of the tip of the cell collector of
A collector that is constructed to enhance the ability of the collector to pick-up clusters or clumps of cells, and to facilitate transfer of collected clusters of cells onto a receiving structure, for example a slide. In one embodiment, a combination of the material of the collector, the texture of the collection surface of the collector, and the use of expansion and rotation of the collector during collection facilitate the collection of cell clusters. Collected clusters of cells can then be transferred from the collector to the receiving structure in such a way as to retain the spatial relationships that existed between the cells in the clusters prior to sampling. Orientation marks on the collector and the receiving structure assist in maintaining the spatial relationship during transfer.
For purposes of explanation, the inventive concepts will be discussed below with respect to the collection of clusters of cells from a cervix to screen for cervical cancer. However, it is to be realized that the inventive concepts can be used to collect cell clusters from other regions of the body for use in screening for other diseases, for example the bladder to screen for bladder cancer, the lungs to screen for lung cancer, breasts to screen for breast cancer, the colon to screen for colon cancer, and the ovaries to screen for ovarian cancer. The clusters of cells can be collected from tissue, urine, induced sputum, breast secretions, cells washed from ovaries, and the like.
FIGS. 1A-C illustrate the concepts of cell cluster collection from a uterine cervix 50.
In addition, the collector 100 has a visible orientation mark 106 to permit the individual collecting the clusters of cells to orient the collector upon sampling of the cervix, and maintain that orientation upon subsequent transfer of cell clusters to a receiving structure 101 which also includes a corresponding orientation mark 108 as shown in
The cell collector 100 can have a number of different configurations as long as it is capable of collecting clusters of cells from both the endo- and ectocervices 56, 62 to ensure collection of cell clusters from the transition zone 58. In one embodiment, a combination of the material of the collector surface 104, the texture of the collector surface 104, and the use of expansion and rotation of the collector surface during collection facilitates the collection of the clusters of cells.
With reference now to FIGS. 2A-C, details of a cervical cell collector assembly 150 embodying the concepts of the invention are illustrated. The collector assembly 150 includes a hollow tube 200 that is detachably connected to an expandable collection tip 201. The tube 200 is made from, for example, plastic or cardboard. The expandable tip 201, which is also the cell collection region of the collector 150, is a resiliently flexible structure that is made of an elastomeric material, for example a thermoplastic elastomer alloy such as Versaflex® CL30 available from GLS Corporation of McHenry, Ill. The expandable tip 201 preferably has a texture that enhances the ability of the collector to collect clusters of cells from the transition zone 58 upon expansion and rotation of the tip 201. For example, the tip 201 can have a texture of MT-11010. Other elastomeric materials could be used for the tip 201, for example microporous polyvinyl acetate, nitrile rubber, nitrile foam, urethane foam, silicone rubber, latex rubber, polyurethane and other elastomers having low durometer, high percent elongation and adequate texture to enhance collection of cell clusters.
The tube 200 is generally hollow from one end 202 to the other end 204, with the end 202 of the tube 200 being open. With reference in particular to
The probe 306 can have a diameter of approximately 2 mm and project beyond the end of the expander probe 305 a distance between approximately 8 to 10 mm. The body of the expander probe 305 forward of the shoulder 324 can have a diameter of approximately 6 mm, while the shoulder 324 has a diameter of approximately 10 mm.
A coil spring 326 is disposed between the shoulder 324 and the end of the outer casing 307 for biasing the expander probe 305 to the left in
The outer tube 307 also includes a tube lock 309. The tube lock 309 comprises a resilient member fixed to the outer tube 307 that projects upwardly through an aperture 332 (see
Returning to
A handle 312 is fixed to a support 313 that is connected to the inner tube 308. The handle 312 is rotatably secured to the support 313 by a pivot 314 to allow the handle 312 to pivot between the position shown in
As best seen in
The user then pushes on the spring cap 311 with the thumb or other digit as shown in
During its movements, the expander probe 305 expands the tip region 210 of the expandable tip 201 into engagement with the endocervix 56. In addition, the shoulder 208 and/or transition section 212 of the expandable tip 201 compresses against the ecto-surface of the cervix 50. As a result, both endocervical and ectocervical cells, including cells from the transition zone 58, can be collected.
The expandable tip 201 is also rotated during collection in order to collect clusters of cells from the transition zone by shearing cell clusters from the transition zone 58 assisted by the texture of the tip 201. The tip 201 is rotated, for example, twenty to thirty degrees. The tip 201 can be rotated by the user manually rotating the handle assembly 303 and the collector assembly 150 connected thereto. Alternatively, the tip 201 can be rotated using a suitable mechanical rotation mechanism which causes rotation of the tip 201 once the tip region 210, shoulder 208 and transition section 212 of the tip 201 are expanded by the handle assembly 303 into contact with the endo- and ecto-cervices.
An example of a mechanical rotation mechanism is illustrated in FIGS. 7A-C.
A gripping sleeve 258 is slidably disposed on the portion 252 and the portion 254 over where the portions 252, 254 connect. Helical teeth (not shown) are disposed on the inside surface of the sleeve 258 for engagement with the teeth 256 on the portion 254.
During use of the assembly 250, after mounting the collector assembly 150 onto the handle assembly 250, as the user inserts the probe, the probe 305 (shown in FIGS. 5A-C) is moved forward, causing the tip 201 to expand (
After insertion, and expansion and rotation to achieve cell cluster collection, the pressure is released and the return spring brings the mechanism back to the original position. The tube lock 309 is depressed and the cervical cell collector assembly 150 is then detached.
The assembly 400 also includes a rear tube 408 having a front end thereof received within the rear end of the tube 402. A slot 410 is formed in the rear tube 408 and a button 412 is slideably disposed in the slot 410. The button 412 is connected to a projection 414 disposed within the slot 406 of the front tube 402.
The button 412 is illustrated in
Once the button 412 is pushed all the way forwardly and the collection tip expanded, the tip is then rotated. The tip can be manually rotated, as discussed above, by manually rotating the rear tube 408. Alternatively, a suitable mechanical rotation mechanism can be provided for rotating the collection tip.
After collection, cell clusters can be transferred from the tip 201 to a receiving structure for subsequent analysis of the cell clusters. Examples of suitable receiving structures include a slide, a petri dish, and other structures to which cells may be transferred for subsequent analysis of the cell clusters. The surface of the receiving structure has greater adhesiveness than the surface of the tip 201 containing cell clusters to enhance the transfer of cell clusters from the tip to the receiving structure. When the receiving structure is a slide, the slide can be provided with a coating that results in the greater adhesiveness.
The tip 201 of the collector 150 is preferably inflated using air during transfer. When the tip 201 is made from a thermoplastic elastomer alloy such as Versaflex® CL30, the elastomer allows uniform expansion of the tip during inflation. During inflation, the tip region 210 and the transition section 212 substantially go away (see
After transfer, the tip 201 can be removed from the tube 200 and put into a container with preservative to preserve remaining cell clusters on the tip 201. The tube 200 can then be discarded or connected to a new tip 201 for further collections. If the tip 201 does not need to be preserved, the tip 201 can be discarded.
With reference now to
The cell sampling region 12 can be a resiliently flexible structure that is made of a suitable elastomeric material such as microporous polyvinyl acetate, thermoplastic elastomer, nitrile rubber, nitrile foam, urethane foam, silicone rubber, latex rubber, polyurethane or any material having suitable low durometer, high percent elongation and surface qualities.
As suggested by
Contact and rotation of the cell sampling member 12 against the surfaces of the cervical os and cervical canal causes exfoliated cervical cells to adhere to the exterior surface of the cell sampling member. Retraction of the pusher 22 withdraws the tip expander 16 from the tip of the cell sampling member 12, thus allowing the cell sampling member to return to its initial extended state. The cervical cell collector 10 may then be removed from the cervical canal 100 and vagina and the cells collected on the surface of the cell sampling member prepared for analysis.
Cell clusters of the ecto- and endocervices are collected using a collector with the characteristics described above. The sample may be collected by a physician or health care worker. Alternately, it should be possible to train women to collect their own samples.
While the invention has been described in conjunction with a preferred embodiment, it will be obvious to one skilled in the art that other objects and refinements of the present invention may be made with the present invention within the purview and scope of the present invention.
The invention, in its various aspects and disclosed forms, is well adapted to the attainment of the stated objects and advantages of others. The disclosed details are not to be taken as limitations on the invention.
This application claims the benefit of U.S. Provisional Application No. 60/642,008 filed Jan. 6, 2005; U.S. Provisional Application No. 60/681,901 filed May 17, 2005; U.S. Provisional Application No. 60/686,150 filed Jun. 1, 2005; U.S. Provisional Application No. 60/708,150 filed Aug. 15, 2005; U.S. Provisional Application No. 60/729,854 filed Oct. 25, 2005; and U.S. Provisional Application No. 60/729,857 filed Oct. 25, 2005. Each of the above-referenced applications is incorporated herein by reference in their entirety.
Number | Date | Country | |
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60642008 | Jan 2005 | US | |
60681901 | May 2005 | US | |
60686150 | Jun 2005 | US | |
60708150 | Aug 2005 | US | |
60729854 | Oct 2005 | US | |
60729857 | Oct 2005 | US |