(12> Ulllted States Patent
`Lonky et al.
`
`US006258044B1
`(16) Patent N6.=
`US 6,258,044 B1
`(45) Date of Patent:
`*Jul. 10, 2001
`
`(54) APPARATUS AND METHOD FOR
`OBTAINING TRANSEPITHELIAL SPECIMEN
`OF A BODY SURFACE USING A
`NON-LACERATING TECHNIQUE
`
`(75) Inventors: Neal M. Lonky, Yorba Linda, CA (US);
`Jeremy James Michael Papadopoulos,
`Milwaukee, WI (Us)
`
`(73) Assigneer 0ralscan/Trylon Joint Venture,
`Suffern, NY(US)
`
`(*) Notice:
`
`This patent issued on a continued pros-
`ecution application ?led under 37 CFR
`1.53(d), and is subject to the tWenty year
`patent term provisions of 35 U_S_C_
`154(a)(2)_
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`(21) Appl, N()_j 09/360,425
`_
`(22) Filed:
`
`Jul. 23, 1999
`
`Related US. Application Data
`(60) Provisional application No. 60/093,910, ?led on Jul. 23,
`1998-
`(51) Int. Cl? ................................................... .. A61B 10/00
`(52) us CL ________________ __
`600/569; @0562
`(58) Field Of Search
`..... .. 600/562 569
`600/570; 604/1; 606/161; 15/DIG. 6, 206,
`207.2
`
`(56)
`
`References Cited
`
`Us PATENT DOCUMENTS
`
`2,675,572 * 4/1954 Nomiya ................................ .. 15/164
`2,839,049
`6/1958 MacLean _
`600/569
`2,955,591
`10/1960 MacLean
`.. 600/569
`4,227,537 * 10/1980 Suciu et al. ..
`600/569
`4,759,376 * 7/1988 Stormby
`.. 128/756
`4,873,992 * 10/1989 Bayne . . . . . .
`. . . .. 600/569
`5,067,195 * 11/1991 Sussman ..
`15/167001
`
`5,184,626
`
`2/1993 Hicken . . . . .
`
`. . . .. 600/569
`
`382/224
`10/1993 Luck er a1,
`5,257,182
`600/569
`5,623,941 * 4/1997 Hedberg et al. .
`. . . .. 600/569
`5,713,369 * 2/1998 Tao et al. . . . . . . . . .
`5,761,760 * 6/1998 Dumler et al. ....................... .. 15/206
`5,937,870 * 8/1999 Gueret ................................ .. 132/218
`
`* Cited by examiner
`
`Primary Examiner—Cary O’Conner
`Assistant Examiner—Charles Marrnor, II
`(74) Attorney, Agent, or Firm—Levisohn, Lerner, Berger &
`Langsam
`
`(57)
`
`ABSTRACT
`
`Anon-lacerational technique to collect cells in an oral mouth
`Cavity utilizes a brush With bristles Which have an abrading
`surface and collect cells from the super?cial, interrnediate
`and basal layers of the Oral tissue
`
`39 Claims, 8 Drawing Sheets
`
`

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`U.S. Patent
`US. Patent
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`Jul. 10, 2001
`Jul. 10, 2001
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`Sheet 1 0f 8
`Sheet 1 0f 8
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`US 6,258,044 B1
`US 6,258,044 B1
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`y "All
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`24
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`22
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`FIG‘. 2
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`

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`U.S. Patent
`US. Patent
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`Jul. 10, 2001
`Jul. 10, 2001
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`Sheet 2 0f 8
`Sheet 2 0f 8
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`US 6,258,044 B1
`US 6,258,044 B1
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`FIG‘. 3
`FIG. 3
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`

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`US. Patent
`U.S. Patent
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`Jul. 10, 2001
`Jul. 10, 2001
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`Sheet 3 0f 8
`Sheet 3 0f 8
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`US 6,258,044 B1
`US 6,258,044 B1
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`U.S. Patent
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`Jul. 10, 2001
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`Sheet 4 0f 8
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`US 6,258,044 B1
`US 6,258,044 B1
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`\
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`'0
`FIG. 5
`S5
`Lk
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`U.S. Patent
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`Jul. 10 2001
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`Sheet 5 of8
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`FIG. 6
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`» W/
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`U.S. Patent
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`Jul. 10, 2001
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`Sheet 6 0f 8
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`US 6,258,044 B1
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`70
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`80
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`F / 6‘ . 7
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`FIG. 8
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`‘I
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`9o
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`92
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`W 94
`Fla 9
`FIG‘. /0A
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`26
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`0W
`7// /// [/w
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`FIG‘. // ?s
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`F/G. lUB
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`U S Patent
`U S Patent
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`Jul. 10, 2001
`Jul. 10, 2001
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`US 6,258,044 B1
`US 6,258,044 B1
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`U.S. Patent
`US. Patent
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`Jul. 10, 2001
`Jul. 10, 2001
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`Sheet 8 0f 8
`Sheet 8 0f 8
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`US 6,258,044 B1
`US 6,258,044 B1
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`F{3* AW?
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`F161 {38'
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`US 6,258,044 B1
`
`1
`APPARATUS AND METHOD FOR
`OBTAINING TRANSEPITHELIAL SPECIMEN
`OF A BODY SURFACE USING A
`NON-LACERATING TECHNIQUE
`
`This application claims the priority of US. provisional
`application Ser. No. 60/093,910 ?led Jul. 23, 1998.
`
`FIELD OF THE INVENTION
`
`The present invention is directed to a method and appa
`ratus for obtaining transepithelial specimens of body sur
`faces using a non-lacerating technique. Speci?cally, the
`invention is directed to tools for sampling squamous epi
`thelium from lesions found in the oral cavity and in similar
`body tissues. The invention is also directed to an improved
`method of testing all lesions that involve the epithelium of
`the oral cavity and/or similar body tissues.
`
`15
`
`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 US. death
`rates for cervical cancer, malignant melanoma and
`Hodgkin’s disease. According to the American Cancer Soci
`ety’s Department of Epidemiology and Surveillance, an
`estimated 30,750 neW cases of oral cancer Were diagnosed
`in the US. during 1997, a ?gure 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 US. deaths Were predicted for 1997.
`There are several reasons for the high mortality rate from
`oral cancer, but undoubtedly, the most signi?cant factor is
`delayed diagnosis. Studies have demonstrated that the sur
`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
`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
`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
`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,
`the multitude of poorly de?ned 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,
`oral manifestations or systemic diseases, in?ammatory 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
`to determine if a suspect oral lesion is pre-cancerous or
`cancerous, is to incise or excise (i.e. lacerate) the lesion
`
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`surgically With either a scalpel or a laser so that a histologi
`cal section of the removed tissue can be prepared for
`microscopic evaluation. Histology can be generally de?ned
`as the microscopic inspection or other testing of a cross
`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 ?oor of the mouth, the dif?culty and
`potential complications of biopsying these lesions, including
`pain, bleeding, and scar formation, can be signi?cant. Not
`infrequently, biopsy is delayed either by the patient due to
`fear of the procedure, or by the clinician due to technical
`dif?culty 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
`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
`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
`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
`scope for evidence of disease.
`Since prior-art cytology is directed toWards the micro
`scopic examination of spontaneously exfoliated cells,
`obtaining the cellular sample is generally a simple, non
`invasive, and painless procedure. Exfoliated or shed cells
`can often be obtained directly from the body ?uid 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
`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
`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
`re?ects their use to sWeep up cells Which Were spontane
`ously exfoliated and present on the super?cial 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
`mal abrasion to the underlying epithelium. These cytology
`sampling instruments therefore either have soft bristles, soft
`
`

`

`US 6,258,044 B1
`
`3
`?exible ?mbriated 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
`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.
`US. 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. US.
`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
`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 BrushTM, a brush that
`has a contoured ?at comb-like head With a single layer of
`?exible plastic bristles (similar to a ?at 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 BrushTM, Which Medical
`Dynamics, Inc. represents is covered by US. 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 ?rst arm,
`creating an L-shape. The center arm is placed Within the
`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
`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
`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
`underneath it and prevent their exfoliation from the surface.
`As noted above, the design of prior art cytology sampling
`instruments re?ect 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 ?exible ?mbriated ends, or even no bristles at
`
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`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
`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
`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
`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
`signi?cant 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
`logic sampling techniques, prior art cytologic techniques
`offer little as a reliable diagnostic alternative to the lacerat
`ing biopsy and histology.
`
`SUMMARY OF THE INVENTION
`
`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 super?cial 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
`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 suf?cient 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 de?ned 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
`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
`
`

`

`US 6,258,044 B1
`
`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
`logic sample. That is, by utilizing the invention disclosed
`herein, cells can readily and consistently be obtained from
`all levels of the epithelium (basal, intermediate and
`super?cial) of a suspect lesion, thus overcoming the limita
`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
`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 in?ammatory
`oral diseases such as pemphigus and lichen planus, oral
`lesions Which represent manifestations of systemic diseases
`such as nutritional de?ciencies 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
`mens of a body surface. The invention relates to a non
`lacerational method and apparatus to obtain such a speci
`men. The reason one seeks to obtain a transepithelial sample
`is because suspect cells appearing at the super?cial 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
`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
`ebeloW because metastases may be suspected depending on
`the cellular architecture existing at just beloW or at the
`basement membrane through to the super?cial 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
`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 transepithelial layer,
`the cell architecture Would be readily apparent, but such an
`approach Would also materially harm the patient. Therefore,
`obtaining a more limited specimen and collection of cells is
`What is desired, and the preferred embodiment of using the
`brush is identi?ed.
`In accordance With the present invention, a toroidal or
`donut shaped brush is provided for cell sampling, as dis
`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.
`The structure of the brush and bristles including the
`stiffness thereof as Well as the shape of the bristle tips
`
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`contribute to the effectiveness of the brushing or scrubbing
`action in retrieving cells from the transepithelial layers. 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
`ered as an assemblage of pentrating edges.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`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
`bristles shoWing the bristle tips.
`FIG. 9 is a side vieW of an alternate structure for abrading.
`FIGS. 10A and 10B 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
`ments of the blunt or square cut bristle ends.
`FIGS. 13A and 13B are electron microscopic enlarge
`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 speci?c 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
`suf?cient 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 dif?
`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 B1
`
`7
`between the thumb and fore?nger While pressed against a
`lesion. Another Way to reach areas that are someWhat
`dif?cult 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
`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 af?xation 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.
`Wires or cables 30 are preferably bent to form an incom
`plete toroid 34 Which is perpendicular to the longitudinal
`axis of handle 20. In other Words, toroid 34 preferably
`de?nes a circular plane, the plane being provided perpen
`dicular to the longitudinal axis of the handle 20 of brush
`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
`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
`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.
`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
`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 identi?ed as a
`cantilever or lateral tip de?ection stiffness. Each end of the
`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 speci?cally made stiff or semi
`rigid, going against the teachings of the art. As described
`above, for example, US. 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 Us. Pat. No.
`4,762,133, is also meant to be soft, as is it provided for
`sampling the exocervix along With the endocervix. This
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`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 super?cial layer of the
`epithelium is not knoWn to have been achieved With prior art
`brushes. In contrast, in the present invention, it is speci?
`cally desired to disrupt the tissue of a lesion and penetrate
`beneath the super?cial layer of the epithelium to sample all
`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
`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
`ably made of Tynex® brand nylon laid in a double layer and
`have a diameter of betWeen 0.010 cm and 0.022 cm. 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 cm 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
`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
`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
`scope enlargements of the front edge or tips of the bristles
`of this invention. The tips of the bristles provid