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`US. Patent
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`Jul. 10, 2001
`Jul. 10, 2001
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`U.S. Patent
`US. Patent
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`Jul. 10, 2001
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`U.S. Patent
`US. Patent
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`Jul. 10,2001
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`U.S. Patent
`US. Patent
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`Jul. 10, 2001
`Jul. 10, 2001
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`U.S. Patent
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`Jul. 10, 2001
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`US 6,258,044 Bl
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`1
`APPARATUS AND METHOD FOR
`OBTAINING TRANSEPITHELIAL SPECIMEN
`OF A BODY SURFACE USING A
`NON-LACERATING TECHNIQUE
`
`This application claims the priority of U.S. provisional
`application Ser. No. 60/093,910 filed Jul. 23, 1998.
`
`FIELD OF THE INVENTION
`
`The present invention is directed to a method and appa(cid:173)
`ratus for obtaining transepithelial specimens of body sur(cid:173)
`faces using a non-lacerating technique. Specifically, the
`invention is directed to tools for sampling squamous epi(cid:173)
`thelium from lesions found in the oral cavity and in similar
`body tissues. The invention is also directed to an improved 15
`method of testing all lesions that involve the epithelium of
`the oral cavity and/or similar body tissues.
`
`2
`surgically with either a scalpel or a laser so that a histologi(cid:173)
`cal section of the removed tissue can be prepared for
`microscopic evaluation. Histology can be generally defined
`as the microscopic inspection or other testing of a cross
`5 section of tissue. This prior art form of oral surgical biopsy
`is generally performed by a surgeon, and is often
`inconvenient, painful, and expensive. Furthermore, since the
`greatest number of oral cancers develop on the lateral border
`of the tongue and floor of the mouth, the difficulty and
`10 potential complications of biopsying these lesions, including
`pain, bleeding, and scar formation, can be significant. Not
`infrequently, biopsy is delayed either by the patient due to
`fear of the procedure, or by the clinician due to technical
`difficulty in obtaining an adequate specimen.
`Since the majority of oral abnormalities detected clini-
`cally prove benign when tested microscopically, and given
`the limitations of biopsy, including cost, inconvenience, pain
`and potential for complications, relatively few oral lesions
`are subjected to biopsy. It is primarily for this reason that
`20 only oral lesions with clinical features strongly suggestive of
`cancer or precancer are referred for biopsy as described in
`the prior art. As a result, many patients with ominous, but
`visually less suggestive lesions are allowed to progress to
`advanced oral cancer, with their condition undiagnosed and
`25 untreated.
`In many body sites, but not the oral cavity, a technique
`known as cytology is commonly utilized as an alternative to
`performing a lacerating biopsy and histological evaluation.
`In these body sites, pre-cancerous and cancerous cells or cell
`30 clusters tend to spontaneously exfoliate, or "slough off"
`from the surface of the epithelium. These cells or cell
`clusters are then collected and examined under the micro(cid:173)
`scope for evidence of disease.
`Since prior-art cytology is directed towards the micro(cid:173)
`scopic examination of spontaneously exfoliated cells,
`obtaining the cellular sample is generally a simple, non(cid:173)
`invasive, and painless procedure. Exfoliated or shed cells
`can often be obtained directly from the body fluid which is
`contiguous with the epithelium. Urine can thus be examined
`for evidence of bladder cancer, and sputum for lung cancer.
`Alternatively, exfoliated or shed cells may be obtained by
`gently scraping or brushing the surface of a mucus mem(cid:173)
`brane epithelium to remove the surrounding mucus using a
`spatula or soft brush. This is the basis for the well known
`procedure known as the Pap smear used to detect early stage
`cervical cancer.
`Because of the ease by which a cellular sample can be
`obtained from these body sites, prior-art cytology is typi(cid:173)
`cally utilized to screen asymptomatic populations for the
`presence of early stage disease. In the cervical Pap smear, for
`example, the entire surface area of the cervical regions
`where cancer generally occurs is gently scraped or brushed
`to collect and test the mucus from those regions. Abrasion of
`the underlying cervical epithelium is undesired, as it can
`cause bleeding and discomfort to the patient. This procedure
`is thus typically performed when no particular part of the
`cervix appears diseased, and when no suspect lesion is
`visible.
`The design of prior art cytology sampling instruments
`reflects their use to sweep up cells which were spontane(cid:173)
`ously exfoliated and present on the superficial epithelial
`surface. Since prior-art cytology brushes need only to gently
`remove surface material, they are designed of various soft
`materials which can collect the cervical mucous with mini(cid:173)
`mal abrasion to the underlying epithelium. These cytology
`sampling instruments therefore either have soft bristles, soft
`
`BACKGROUND OF THE INVENTION
`
`Cancers of the oral cavity and pharynx are a major cause
`of death from cancer in the U.S., exceeding the U.S. death
`rates for cervical cancer, malignant melanoma and
`Hodgkin's disease. According to the American Cancer Soci(cid:173)
`ety's Department of Epidemiology and Surveillance, an
`estimated 30,750 new cases of oral cancer were diagnosed
`in the U.S. during 1997, a figure which accounts for 2% to
`4% of all cancers diagnosed annually.
`Despite advances in surgery, radiation, and chemotherapy,
`the mortality rate of oral cancer has not improved in the last
`20 years. Ultimately, 50% of patients die from their
`malignancy, and 8,440 U.S. deaths were predicted for 1997.
`There are several reasons for the high mortality rate from
`oral cancer, but undoubtedly, the most significant factor is
`delayed diagnosis. Studies have demonstrated that the sur- 35
`vival and cure rate increase dramatically when oral cancer is
`detected at an early stage. For example, the 5-year survival
`rate for patients with localized disease approximates 79%
`compared to 19% for those with distant metastases.
`Unfortunately, approximately two thirds of patients at time 40
`of diagnosis have advanced disease, and over 50% display
`evidence of spread to regional lymph nodes and distant
`metastases.
`Delay in the diagnosis of oral cancer is often the result of
`the limited diagnostic tools available in the prior art. The 45
`dentist or physician who detects an oral lesion which is not
`clearly suggestive of a precancer or cancer clinically, and
`who is limited to the prior art tools and methods, is faced
`with a quandary. Approximately 5-10% of adult patients
`seen in a typical dental practice exhibit some type of oral 50
`lesion, yet only a small proportion (approximately 0.5% to
`1 %) are precancerous or cancerous. These oral lesions are
`commonly evidenced as a white or reddish patch, ulceration,
`plaque or nodule in the oral cavity. The overwhelming
`majority of these lesions are relatively harmless; however, 55
`the multitude of poorly defined lesions in the oral cavity can
`be confounding to the clinician. A diverse group of oral
`lesions may be easily confused with malignancy, and
`conversely, malignancy may be mistaken for a benign
`lesion. Benign tumors, reactive processes, traumatic lesions, 60
`oral manifestations or systemic diseases, inflammatory oral
`disorders, and bacterial, viral and fungal infections all
`display similar oral features thereby impeding establishment
`of an accurate clinical diagnosis.
`The only reliable means currently available in the prior art 65
`to determine if a suspect oral lesion is pre-cancerous or
`cancerous, is to incise or excise (i.e. lacerate) the lesion
`
`10
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`US 6,258,044 Bl
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`4
`all. Since prior-art cytology brushes only need to gently
`remove surface material, they are designed of various soft
`materials which can collect the cervical mucous with mini-
`mal abrasion to the underlying epithelium.
`While abnormal cells can spontaneously exfoliate to the
`epithelial surface and be gently removed by prior art instru(cid:173)
`ments in the uterine cervix and other similar tissues, in many
`oral cavity lesions the abnormal cells never reach the surface
`because they are blocked by the keratin layer. This limitation
`10 is a major cause of the high false negative rate of prior art
`cytological testing to detect lesions of the oral cavity. That
`is, a large proportion of oral lesions found to be positive
`using lacerating biopsy and histology are found to be
`negative using cytology. In one major study, this false
`15 negative rate was found to be as high as 30%.
`It is largely due to this lack of correlation between
`histology and prior art oral cytology that there is currently no
`significant use of oral cytology in the United States or
`elsewhere to test questionable oral lesions. Since it is well
`known that dangerous, truly cancerous oral lesions may
`commonly be reported as "negative" using prior art cyto(cid:173)
`logic sampling techniques, prior art cytologic techniques
`offer little as a reliable diagnostic alternative to the lacerat(cid:173)
`ing biopsy and histology.
`
`25
`
`SUMMARY OF 1HE INVENTION
`
`3
`flexible fimbriated or fringed ends, or even, as in the case of
`the cotton swab or spatula, no bristles at all.
`Examples of prior art cytological sampling tools include
`the wooden, metal or plastic spatula. According to the
`traditional method of Pap smear sampling, the spatula is 5
`placed onto the surface of the cervix and lightly depressed
`or scraped across the surface of the cervix to pick up
`exfoliated cells.
`Further examples of prior art cytological sampling tools
`include the Cytobrush®; a device which uses soft and
`tapered bristles to sample shed cells from the cervical canal.
`U.S. Pat. No. 4,759,376, which allegedly covers this
`product, likewise describes a conical tapered soft bristle
`brush (a mascara brush shape) which is placed into the
`cervical canal and rotated for endocervical sampling. U.S.
`Pat. No. 4,759,376 teaches that the bristles "are to be
`relatively soft such as that of a soft toothbrush to more
`readily bend and avoid damaging the tissues." By way of
`further example, physicians have long used the common
`swab, commercially known as the Q-Tip®, to perform 20
`endocervical sampling.
`Other prior art cytological sampling tools designed to
`obtain a cytological sample from the cervix may combine
`both endocervical and exocervical sampling regions into one
`device. These devices swab the surface of mucous-covered
`tissue by soft brushing the mucous layer of the endocervix
`and exocervix at the same time, thereby collecting the cells
`contained in the mucous layer tissue of those surfaces. These
`devices include the Unimar®-Cervex Brush™, a brush that
`has a contoured fiat comb-like head with a single layer of
`flexible plastic bristles (similar to a fiat paint brush having
`only one row of bristles) in which the center bristles are
`longer than the bristles on the ends. According to the method
`of use for the device, the center bristles are inserted into the
`cervical canal until the lateral bristles bend against the
`exocervix. The device is then removed and the cells are
`swabbed across a microscope slide similar to painting with
`a paintbrush.
`Similarly, the Bayne Pap Brush™, which Medical
`Dynamics, Inc. represents is covered by U.S. Pat. No.
`4,762,133, contains a center arm, made of soft DuPont
`bristles, running horizontal to the cervical canal and a
`second arm of soft bristles at ninety degrees to the first arm,
`creating an L-shape. The center arm is placed within the 45
`cervical canal and then rotated. Upon rotation, the soft
`bristles of the second arm automatically sweep the surface of
`the exocervix in a circular motion thereby sampling the
`exocervix along with the endocervix.
`Although cytology has been adopted for use in several 50
`other body sites, it has not been found useful to test
`questionable lesions of the oral cavity. This is in large part
`due to the fact that the prior art devices and methods used to
`obtain a cellular sample for cytology are unsatisfactory
`when used to sample lesions of the oral cavity and similar 55
`epithelia. Unlike the uterine cervix, questionable lesions of
`the oral cavity and similar epithelia may be typically coated
`with multiple layers of keratinized cells. This "keratin layer"
`forms a relatively hard "skin-like" coating over the surface
`of the lesion and may thus hide the abnormal cells lying 60
`underneath it and prevent their exfoliation from the surface.
`As noted above, the design of prior art cytology sampling
`instruments reflect their use in tissues where spontaneously
`exfoliated abnormal cells are commonly present on the
`surface of an area of epithelium that harbors disease. These
`cytology sampling instruments therefore either have soft
`bristles, soft flexible fimbriated ends, or even no bristles at
`
`35
`
`30
`
`It is an object of the present invention to provide an
`apparatus and method for sampling epithelial cells from the
`anatomy without the pain or injury of lacerational biopsies.
`It is a further object of the present invention to provide an
`apparatus for sampling epithelial tissue in the oral cavity, the
`vulva, and similar keratinized epithelia.
`It is a further object of the present invention to provide a
`non-lacerating apparatus for readily sampling cells from all
`levels of a surface epithelial lesion, including the basal,
`intermediate and superficial layers of the lesion.
`It is a further object of the present invention to provide an
`apparatus for sampling cells from the entire surface of a
`40 lesion, to completely sample a suspect lesion which may be
`multifocal.
`Further objects of the invention will become apparent in
`conjunction with the disclosure herein.
`In accordance with the present invention, an apparatus is
`provided for sampling all types of epithelium, particularly
`squamous epithelium, from lesions found in the oral cavity,
`the vaginal cavity, and other similar keratinized epithelia.
`Further in accordance with the invention, an improved
`method is provided for testing questionable lesions found in
`the epithelium of the oral cavity and other body tissues. The
`method invented involves exerting sufficient pressure in the
`lesion area with a surface or edge capable of dislodging cells
`in and under a keratinized layer.
`For purposes of this patent application, the prior art
`scalpel procedure is defined as lacerational, whereas the
`novel invention herein is non-lacerational and therefore
`minimally invasive. To the extent that an abrasive brush has
`characteristics that may cause minor discomfort and/or
`bleeding, there is substantial difference between the prior art
`scalpel trauma and the minimal trauma associated with the
`present invention.
`In accordance with the present inventions, focal sampling
`of questionable lesions of the oral cavity and of similar
`65 epithelia is provided using a specialized, stiff-bristled, brush
`device disclosed herein. By rubbing harder than normal
`cytological sampling, and using a device which penetrates
`
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`US 6,258,044 Bl
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`6
`contribute to the effectiveness of the brushing or scrubbing
`action in retrieving cells from the transepitheliallayers. The
`shape of the bristle tips is determined by the bristle cutting
`process. The bristle tips, preferably, have scraping edges.
`The tips of the brush and the brush itself may be consid(cid:173)
`ered as an assemblage of pentrating edges.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`5
`epithelium but not very deep on each stroke, one can reach
`to the basement membrane without lacerating. As opposed
`to the prior art, use of the device allows cell sampling which
`can readily and consistently produce a transepithelial cyto(cid:173)
`logic sample. That is, by utilizing the invention disclosed 5
`herein, cells can readily and consistently be obtained from
`all levels of the epithelium (basal, intermediate and
`superficial) of a suspect lesion, thus overcoming the limita(cid:173)
`tion in the prior art of abnormal epithelial cells being
`inaccessible to cytology for a variety of reasons, including
`because they are covered by a keratin layer. The resulting
`cellular sample functionally approximates the cellular
`sample of a lacerating biopsy device, but is obtained with the
`ease of a swab application, and without discomfort to the
`patient. The subject invention therefore makes practical the 15
`routine testing of questionable lesions of the oral cavity, thus
`allowing early detection and treatment of oral cancer and
`pre-cancer. Furthermore, the invention can be utilized in
`testing benign neoplasms, a diverse group of inflammatory
`oral diseases such as pemphigus and lichen planus, oral
`lesions which represent manifestations of systemic diseases
`such as nutritional deficiencies and anemia, viral, bacterial,
`and fungal infections, reactive and traumatic processes, and
`chromosomal sex determination.
`While the preferred embodiment has been described with
`respect to a brush, the present invention generally describes
`a method and apparatus for obtaining transepithelial speci(cid:173)
`mens of a body surface. The invention relates to a non(cid:173)
`lacerational method and apparatus to obtain such a speci(cid:173)
`men. The reason one seeks to obtain a transepithelial sample 30
`is because suspect cells appearing at the superficial layer of
`the epithelium originate at the basal layer within the tissue.
`With respect to the oral cavity, basal cells originate in the
`general area of the basement membrane separating the
`epithelial tissue from the tissue below the membrane known 35
`as the submucosa. In determining whether or not a patient
`has a precancerous or cancerous condition, it is important to
`reach down to the basement membrane and slightly ther(cid:173)
`ebelow because metastases may be suspected depending on
`the cellular architecture existing at just below or at the 40
`basement membrane through to the superficial layer.
`Alternate ways to obtain such a transepithelial specimen
`without laceration include electromagnetic, optical,
`microwave, ultrasound, mechanical and chemical. With
`regard to chemical, it is possible that the enzyme hyalurona- 45
`dase could be used since this chemical could separate the
`epithelium from between the basement membrane. If one
`could actually obtain the entirety of a transepitheliallayer,
`the cell architecture would be readily apparent, but such an
`approach would also materially harm the patient. Therefore, 50
`obtaining a more limited specimen and collection of cells is
`what is desired, and the preferred embodiment of using the
`brush is identified.
`In accordance with the present invention, a toroidal or
`donut shaped brush is provided for cell sampling, as dis- 55
`closed below. The brush provides a more complete sampling
`of the epithelium than the brushes of the prior art. In
`accordance with the present invention, a method is further
`provided for sampling epithelial cells. According to the
`method, the brush of the present invention may be rotated
`against or brushed parallel to, an epithelial surface, to
`burrow into and deeply sample epithelial cells. A rotation
`motion or other scrub motion essentially operates to scrub
`across the lesion thereby causing cells to be lifted from the
`surrounding tissues and adhere to the bristles of the brush. 65
`The structure of the brush and bristles including the
`stiffness thereof as well as the shape of the bristle tips
`
`20
`
`10
`
`FIG. 1 is a perspective view of an apparatus for sampling
`epithelial tissue in accordance with the present invention.
`FIG. 2 is a side view of the apparatus for sampling
`epithelial tissue shown in FIG. 1.
`FIG. 3 is a perspective view of using the brush of the
`present invention to sample a lesion, in accordance with the
`method of the present invention.
`FIG. 4 is an enlarged perspective view of the brush of this
`invention.
`FIG. 5 is a side view of the enlarged view of the brush of
`this invention shown in FIG. 4; and
`FIG. 6 is an end view showing the bristles of the brush
`shown in FIG. 4.
`FIGS. 7 and 8 are side views of alternate structures for the
`25 bristles showing the bristle tips.
`FIG. 9 is a side view of an alternate structure for abrading.
`FIGS. lOA and lOB are alternate brush structures.
`FIG. 11 is a sectional view of the tissue in the oral cavity
`showing the brush penetrating the basement membrane and
`reaching to the submucosa.
`FIGS. 12A and 12B are electron microscopic enlarge(cid:173)
`ments of the blunt or square cut bristle ends.
`FIGS. 13A and 13B are electron microscopic enlarge(cid:173)
`ments of the wedge or chisel cut bristle ends.
`
`DETAILED DESCRIPTION OF THE
`INVENTION AND THE PREFERRED
`EMBODIMENTS
`
`FIGS. 1-3 were submitted with the original provisional
`patent application. FIGS. 4--6 are more detailed and more
`accurate representations of the brush and bristle structure
`including its specific construction. Submitted in this detailed
`description are photographs taken by an electron microscope
`of the ends of the bristles further illuminating the structural
`aspects of the bristles which contribute to the effectiveness
`of the brush in obtaining transepithelial samples.
`A preferred embodiment of the invention is provided in
`FIG. 1. In accordance with the invention, a device 18 is
`provided which comprises a handle or elongate member 20,
`having both a proximal end 22 and a distal end 24. In the
`preferred embodiment, the total length of the device is
`approximately six inches.
`Handle 20 is designed for gripping by a user, and is of a
`sufficient length to allow the user to manipulate the device
`within a body cavity from a location just outside the body.
`In the preferred embodiment, handle 20 is semi-rigid so as
`to assist in reaching the target tissue notwithstanding diffi-
`60 cult angles or narrow passages. In the preferred
`embodiment, the handle is approximately 5 inches long.
`The brush handle can be constructed of a plastic, such as
`polypropylene, or any other suitable semi-rigid material.
`The handle can be solid, but is hollow in the preferred
`embodiment. It is further preferred that handle 20 also have
`at least one area whose cross-section is substantially circular
`such that the elongate member may be readily twirled
`
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`US 6,258,044 Bl
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`7
`between the thumb and forefinger while pressed against a
`lesion. Another way to reach areas that are somewhat
`difficult in the oral cavity would be to hold the handle short
`and rotate and scrub the side of the brush, rather than its end,
`against the lesion area. This will also be effective in the 5
`brush bristles passing through the transepithelial layers to
`retrieve cells in the lesion area.
`At or around the distal end 24 of the handle or elongate
`member 20, the device is provided with a brush head 26.
`Brush head 26 is preferably a substantially toroidal or
`"donut" shaped brush which presents bristles both towards
`its end and side, and can be formed from one or more twisted
`or braided wires, backbone or cables 30. Wires or cables 30
`are preferably secured to handle 20 by affixation to backbone
`or the wire 30 in a recess 36 located in the distal end 24 of
`the handle. The brush can be formed from conventional
`twisted wire brush construction. In a preferred embodiment,
`the total length of the twisted wire is approximately 1.1
`inches, with approximately 0.2 inches inserted in the handle,
`and approximately 0.9 inches exposed as part of the toroid. 20
`Wires or cables 30 are preferably bent to form an incom(cid:173)
`plete toroid 34 which is perpendicular to the longitudinal
`axis of handle 20. In other words, toroid 34 preferably
`defines a circular plane, the plane being provided perpen(cid:173)
`dicular to the longitudinal axis of the handle 20 of brush 25
`head 26. Alternatively, a cross-section of the brush forms a
`nautilus or spiral shape at ninety degrees to the handle or
`elongate member 20. The brush could be curled into an
`outward spiral in the same plane. The metallic spine of the
`brush spirals out in a plane which is perpendicular to the 30
`handle. This is more clearly seen in FIGS. 4-6.
`Brush head 26 may be integral with handle 20, or may be
`detachable. It may be a reusable sterilizable or surgical
`holder. Alternatively, the proximal end 22 of the handle 20
`may be detachable from the distal end 24. The detachable
`portion of the brush may be scored, to easily break away,
`may be provided with screw threads to screw off the
`remainder of the device, or so forth. In either embodiment,
`detachment of either the brush head or of a portion of the 40
`handle connected to the brush head, can allow the distal end
`of the brush, having sampled cells collected therein, to be
`separated from the proximal end. This allows the handle or
`the proximal end thereof to be discarded while the distal end
`of the apparatus is forwarded to the laboratory for analysis. 45
`The bristles are also used to collect cells as well as perform
`the transepithelial activity. For example, the distal portion of
`the device can be dropped into a transfer solution, while the
`proximal portion is thrown away.
`Brush head 26 is further provided with a plurality of 50
`bristles 40. In the preferred embodiment, bristles 40 are
`approximately 0.25 inches from tip to tip, protrude 0.05--0.2
`inches from the toroidal wire and have a stiffness of between
`0.04--0.2 lbs/inch. The stiffness is better identified as a
`cantilever or lateral tip deflection stiffness. Each end of the 55
`bristle protrudes a distance of about 0.10 inches from the
`wire spine. The bristles are approximately 0.006 inches
`(0.16 mm) thick.
`Although in the prior art, the sampling brushes provided
`have been soft brushes with soft bristles, in the present
`invention, bristles 40 are specifically made stiff or semi(cid:173)
`rigid, going against the teachings of the art. As described
`above, for example, U.S. Pat. No. 4,759,376 teaches that the
`bristles of the brush should be relatively soft and should
`readily bend Likewise, the brush disclosed in U.S. Pat. No.
`4,762,133, is also meant to be soft, as is it provided for
`sampling the exocervix along with the endocervix. This
`
`8
`preference heretofore in the art to use a soft brush prevents
`damage to tissue. While this is generally desirable in the
`cervix, it is not helpful when the lesions are keratinized, as
`in the oral cavity.
`Moreover, sampling below the superficial layer of the
`epithelium is not known to have been achieved with prior art
`brushes. In contrast, in the present invention, it is specifi(cid:173)
`cally desired to disrupt the tissue of a lesion and penetrate
`beneath the superficial layer of the epithelium to sample all
`10 three epithelial layers. Whereas the prior art brushes are
`generally designed for the cervix where no keratin is present,
`the present brush can penetrate through keratin covered
`lesions to provide a suitable tissue sample. It may be
`preferable to have a plurality of scratches or furrows in the
`15 tissue from the brush, one of which will penetrate the
`basement membrane over a substantial area of the lesion. In
`the present invention, each stroke penetrates a little so that
`the depth of penetration can be controlled by the appearance
`of spot bleeding.
`Accordingly, in the present invention, bristles 40 of brush
`head 26 are each stiff or semi-rigid. The bristles are prefer(cid:173)
`ably made of Tynex® brand nylon laid in a double layer and
`have a diameter of between 0.010 em and 0.022 em. The
`Tynex® brand bristles have their own cantilever stiffness
`which may be at a modulus of 500,000 psi. Preferably, the
`bristles have a diameter of approximately 0.016 em and
`protrude 0.10 inches from the wire spine. Although triple
`and single row densities may be used, double row density
`bristles are preferred. A range of protruding lengths of 0.08
`to 0.16 inches could be used.
`Bristles 40 are preferably provided in a series of arrays 42.
`As shown in FIG. 1, each array 42 is composed of a series
`of bristles 40, the bristles extending radially from a center
`44, to form each of the arrays 42. At center 44, the end of
`35 each bristle 40 is secured within the twisted wire 30 back-
`bone.
`Arrays 42 preferably extend around the entire perimeter
`of toroid 34. In one embodiment, viewing the apparatus
`head-on, from the perspective "A" in FIGS. 1 or 2, tufts of
`bristles are evenly arranged around the perimeter of the
`toroid. Thus, the arrays are arranged at 30 degrees spacings
`along the twisted wire of the brush head.
`The bristles do not form a plane, but rather preferably
`extend upward from center 44 at an acute angle to wire 30.
`As a result of this bristle orientation, rotation will result in
`a degree of bristle abrasion that is effected by the bristles
`splaying under load. Rotation in the opposite direction will
`result in abrasion that is greatly accentuated by maximizing
`the direct piercing of the skin with the stiff bristle ends.
`While the unique drilling combination of bristle pressure, tip
`shape, stiffness, brushing and rotation results in provision of
`the trans-epithelial cytologic sample of the lesion as noted
`above, rotation in the direction which moderates direct
`surface piercing by the bristle ends (clockwise, in the case
`of the preferred embodiment) allows this trans-epithelial
`cytologic sample to be obtained with minimal discomfort to
`the patient.
`Further, an advantage and feature of this invention
`60 achieved with the brush is that a rather large area around the
`lesion area is subject to the action of the brush which
`enhances the cell collection process to provide a more
`effective sampling.
`The photographs of FIGS. 12A-12D are electron micro-
`65 scope enlargements of the front edge or tips of the bristles
`of this invention. The tips of the bristles provide good
`scraping or cutting surfaces. These scraping or cutting
`
`13
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`

`

`US 6,258,044 Bl
`
`5
`
`9
`surfaces help to dislodge the cells from the surrounding
`tissue to be collected on the bristles. The sharp edges do not
`dig too deeply into the epithelial tissue and avoid severe
`injury.
`FIGS. 7 and 8 are cross sectional views of alternate brush
`structures with the front edges of the bristles 70 being
`squared as in FIG. 7 or "file card wire brush type edges" 80
`which are aligned as in FIG. 8. The squared britles of FIG.
`7 form non-penetrating scraping edges and even generate
`negative rake angles when the bristles bend over. Both 10
`brushes are attached to handles 72 and 82 respectively. It is
`preferable to have a large number of such bristles to spread
`the pressure as the brush structure is being used. An alter(cid:173)
`native structure in FIG. 9 illustrates a plurality of small rigid
`scrapers 90 which could be employed at the edge of the
`brush and attached to handle 92. Such scrapers would extend 15
`from handle 92.
`FIGS. lOA or lOB illustrate conventional brush arrange(cid:173)
`ments 94 and 96 adjoined to a handle allowing end or side
`pressure. These brushes can be rubbed back and forth to
`dislodge and remove the cells for their collection. A plurality 20
`of different abrasive materials such as finely ribbed or
`bumpy materials could be employed, where the protrusions
`may be shaped with edges to apply highly localized
`pressure, and catch against cell clusters rather than sliding
`over them. FIGS. 4 through 6 are respectively perspective 25
`side and end views of an enlargement of the brush of this
`invention. The bristles 40 are seen collected and captured in
`the metallic wire 30 to form a relatively irregular surface
`although the side view in FIG. 5 illustrates that the front
`plane 52 of the brush head 26 presents a relatively fiat planar 30
`surface. In use, only the outer front plane 52 or the edge
`planes 54 of the brush head will be used to retrieve cells
`from the epithelial tissue structure. The following is a list of
`alternative models for materials which could sample cells.
`Such materials would generally not be introduced into a 35
`patient's mouth.
`
`10
`maintaining enough separation between the bristles to trap a
`clinically effective amount of cells. The length of the stiff
`bristles of the brush may also