WO1999021521A1

WO1999021521A1 - Vaginal introitus sampling system

Info

Publication number: WO1999021521A1
Application number: PCT/AU1998/000894
Authority: WO
Inventors: Jagmohanbir Singh Dillon; William Leonard Mobbs
Original assignee: Noble House Group Pty. Ltd.
Priority date: 1997-10-24
Filing date: 1998-10-26
Publication date: 1999-05-06
Also published as: AUPO999997A0

Abstract

Device and methods for obtaining samples of cellular material from the vaginal introitus are disclosed which, typically, vaginal fluid is adsorbed by a body through a semi-permeable membrane which retains the cellular material. In one form, the device (500) comprises a tampon-like body (502) having a highly adsorbent portion (502b) and a soft but less permeable proximal portion (502a). A semi-permeable membrane (504) is fitted over the body (500). A string (508) is provided to withdraw the body (500) from the vaginal introitus after it has been indwelling therein for some minutes or hours. Fluid imbibed by the body (500) must pass through the membrane and leave behind any cellular material. Upon withdrawal of the device, the filter-like membrane (504) is inverted to protect the sample material from contact with the wall of the vaginal canal. The membrane (504) can be easily removed from the device (500) and the sample material recovered for analysis.

Description

TITLE: VAGINAL INTROITUS SAMPLING SYSTEM

TECHNICAL FIELD

This invention relates to means for collecting and handling biological samples 5 from the vaginal introitus It is particularly, though not exclusively, concerned with devices and methods adapted for self-use, that is, for women themselves to use at home The samples obtained may be used to detect abnormal tissue cells from the cervix, endometπum or vagina, to detect and characterise pathogens, to determine uterine pH, to sample post-coital fluids or to determine the time of o ovulation

Normally medical or paramedical specialists using laboratory facilities will examine the samples obtained as disclosed herein However, the sample collecting means of this invention are also applicable for use with various 5 indicators and/or diagnostic kits that can be employed at home by the user

BACKGROUND TO THE INVENTION

It is well recognised that many women who need to have uterine or cervical samples taken are reluctant to visit a physician for examination for personal or o cultural reasons Accordingly, the prior art is replete with devices which will allow a woman to take her own samples of cervical tissue cells or vaginal fluids Without exception, however, the devices of the prior art are rigid mechanical devices, which are inserted, manipulated and immediately withdrawn These devices have many disadvantages 5 • Women who are reluctant to visit a physician for a cervical examination are likely to find the use of such mechanical contrivances repugnant • Being rigid or semi rigid with the intention of making forceful contact with the cervix to remove tissue cells therefrom, such devices can damage the uterine vault and cervix and lead to infection 0 • Many of these mechanical devices are crooked in shape, having an angled head portion intended to contact a normally located cervix, but not only is the location of the cervix in relation to the uterine introitus highly variable, many women cannot determine by feel whether contact has been made with the cervix or the vaginal vault. • The devices require careful manipulation, not only to ensure proper contact between the sampling swab or brush and the cervix, but also to avoid discomfort or even injury. • In part, no doubt, because they are not used correctly (being unpleasant to use) and in part because they can only take instantaneous samples, it is not surprising that the samples collected by such devices frequently yield false- negative results. 0

Most relevant prior art devices employ a brush or swab on the end of a plunger that slides in a protective tube. Many devices of this type (such as US patents 4,157,709 and 4,318,414 to Schuster, 4,628,941 and to Kosasky, 4,877,0337, 4,877,037 to Ko, and 3,776,219) employ angled or crooked tubes which are 5 intended to place the brush, scraper or swab in contact with the cervix. Some (such as those disclosed by the above Schuster patents, US patent 5,129,402 to Koll et al, 3,776,219) disclose the use of a tube which opens, petal-like, when the brush is extruded therefrom. Others, such as that the above patent to Kosasky disclose the use of cup on the end of the tube which is normally covered by 0 leaves that are deflected by the cervix (when the device is precisely positioned) to expose the sampling swab or brush. Yet other devices (eg, US those disclosed in US patent Nos. 5,787,891 to Sak, 5,445,164 to Worthen, 4,485,824 to Koll and 4,784,158 to Okimuto) employ straight tubes from which a swab or brush can be extruded for sampling and then withdrawn. Or, as disclosed in US patent 5 4,534,362 to Schumacher and US patent 4,131 ,112, the straight tube may serve as a syringe in which the plunger is withdrawn to suck in vaginal fluid. The latter devices have the added disadvantage that the open end of the tube is immediately blocked by the vaginal wall as soon as the plunger is withdrawn; indeed, considerable discomfort if not injury could result if the plunger is further o withdrawn and then the tube is withdrawn without waiting for pressure equalisation. It is well known to smear samples from the swabs brushes or the like collection means of the prior art onto microscopic slides, to fix and/or stain them and to examine them under the microscope for abnormal cells and/or bacteria It is also known to wash the swabs in a fixing solution, to concentrate the cells 5 transferred to the solution in filtration step and to then transfer the filtrate to a microscopic slide for examination Indeed, the latter procedure can be carried out in a substantially automatic manner using the proprietary ThinPrep® process [See "ThinPrep Processor", Wilbur et al, AJCP, Vol 101 No 2, February 1994, pp 209-214] However, since the swabs are far from saturated, placing them in the o fixative solution will tend to drive the collected cells further into the swab as the swab imbibes the solution Unless the rinsing is done with great care and thoroughness much of the sample can be lost in this manner

OBJECTIVES OF THE INVENTION 5 It is therefore an object of the present invention to provide improved means for the collection and handling of biological samples from the vaginal introitus which will not suffer from one or more of the problems outlined above in relation to the prior art

0 OUTLINE OF INVENTION

From one aspect, the present invention is based upon the realisation that the lack of reliability commonly associated with self-sampling can be more than compensated by the use of an indwelling sampling device, since this greatly extends the period of time during which a sample is collected and does not 5 require precise location in relation to the cervix As a result, more sample material is collected and the chance that rare abnormal cells shed from the cervix will be captured is greatly increased It was also appreciated that most women who are reluctant to present to their physicians for vaginal examination are quite at home with the self-insertion and removal of tampons, both with and without the use of 0 simple tubular applicators

From one aspect, the sample collection means of the invention comprises (i) a resilient and pliable body having a shape and configuration that adapt it for retention in the vagina with its distal end within the vaginal vault near the cervix,

(ii) sample retention means on the distal end of the body adapted to retain vaginal mucosa and cellular material and (iii) means for withdrawing the body from the vagina. [The terms 'distal' and 'proximal' are used herein to signify the 5 inner and outer portions of the device, when inserted, in order to be consistent with the conventional usage of these terms that takes the physician's perspective.]

The body is preferably such that it can be readily and fully inserted into the o vagina by the user and wholly retained therein so that the user can undertake normal duties while the device is indwelling (as in the case of tampons). The body may be of a generally spherical or oblate shape, or it may be cylindrical in shape, a cylinder of about 45 - 65 mm long and 12 - 15 mm in diameter being known to be resistant to expulsion and to present its distal end at or near the 5 cervix. Such a body could have a figure-of-eight section (rather than a circular section) so that it conforms more naturally and closely to the anatomical cross- section of a relaxed vagina. The body may be solid or hollow. It may be cup- shaped with a proximal open end for attachment to an applicator rod (if used), or cup-shaped with an open distal end adapted to accommodate a swab-like sample o retention means.

Though preferably formed from fibrous or open-cell sponge materials that are strongly water adsorbent, the body may also be made of materials - such as closed-cell sponges - which are not water adsorbent. Biocompatible open and 5 closed cell synthetic sponges suitable for use as the body are commercially available, for example from Lunde Manufacturing Corp of Minneapolis, USA. Adsorbent biocompatible fibrous materials suitable for use in the body are typically those employed for swabs, wound dressings and tampons; for example, a mix of treated cellulose and polyester fibres. Such materials are well known to 0 those skilled in the art.

Where the body is not adsorbent, the sample retention means may be swab-like and adsorbent, it may present a fibrous surface that is adapted to capture vaginal mucous or it may carry a natural charge which assists the capture of cellular material. Where the body is adsorbent, the sample retention means preferably comprises a semi-permeable membrane that acts as a filter, allowing water to pass into the body but retention cellular and other matter on its external surface. 5 The membrane may also have a fibrous and/or charged surface to assist in the capture of mucosa and cells.

The sample retention means may be arranged to be readily separable from the body (after the sampling means has been removed from the vagina) so that it can 0 be further processed without the body. For example, the sample retention means can be rinsed by itself in a fixative solution, avoiding the loss of sample material into the body. Or, sample material from the retention means can be transferred directly to a microscope slide for fixing and examination.

5 The formation of the sample retention means as a detachable layer or membrane on the distal end of the body enables it to invert upon withdrawal and to thereby protect the collected sample material from being rubbed off on the vaginal wall. Of course, the membrane is attached to the body (usually that at the centre of the distal portion of the body) so that it is withdrawn with the body and not left in the o vagina. The use of an inverting sample retention layer or membrane eliminates the need for the conventional rigid protective tube that is universally used to retrieve and guard the sample material in the prior art. It therefore adapts the sampling means for self-insertion, indwelling use and withdrawal, like the familiar tampon. 5

The semi-permeable membrane of the sample retention means may be made using technology well known in the filter art. It may be a sheet of synthetic material having holes of known size formed therein, or it may be a fibrous paperlike or fabric-like material having a pore size sufficiently small to retain tissue and 0 bacterial cells. However, the membrane is preferably hydrophilic, should allow water to flow readily there-through to the supporting adsorbent body and, preferably, should carry a charge that assists in the retention of cellular material. Of course, the membranes need to be biocompatible and certified for use within the human body. Semi-permeable membranes meeting these requirements are commercially available from manufactures such as Whatman of Kent, UK,

Osmonics of Livermore, CA, USA, Pall Gelman Sciences of Ann Arbor, Ml USA, or Corning Science Products Division, Acton, MA, USA.

5

Whether or not the sample retention means is inverting or is fully attached to the distal portion of the body, it is envisaged that a protective skirt-like membrane can be used which will invert over the distal end of the body during withdrawal to protect the sample retention means against rubbing on the vaginal wall. Such a o protective membrane should not be adapted to retain sample material and need not be porous, though it should be comfortable to insert and withdraw. Again, materials of this nature are well known in the biomaterials art.

Though the use of indwelling sample collection means is preferred, the above 5 disclosed features may be applied to self-sampling means which incorporate an applicator rod or tube and which are, therefore, intended for the collection of an 'instantaneous' sample. Thus, an absorbent body may be affixed to the distal end of the applicator and an inverting sample-retention membrane may be fitted over the body, as before. Alternatively, a swab-like sample retention means may be 0 fixed to the applicator and a protective skirt-like inverting membrane used. As already noted, the use of inverting membranes avoids the need for the swab and sample to be withdrawn into a protective tube and, therefore, permits the use of a thin and inexpensive applicator rod.

5 An applicator may also be used for the insertion of the indwelling sampling means of the present invention, if desired. This allows another useful variation if the design of the sampling means to be implemented. If a soft compressible open-cell sponge is used for the body and a semi-permeable membrane is used for the sample retention means, the body can be used as a pump to draw liquid through o the membrane. This feature can be exploited by using an applicator tube to hold the body in a compressed stated until it is released in the vaginal vault, whereupon the sponge of the body will expand and draw fluid from the vault into it through the membrane. To prevent the fluid from bypassing the membrane, the entire body may be covered by the membrane, or the portion which is not so covered (normally the proximal portion) may be sealed or covered with an impermeable layer. Preferably, the filter-like membrane will be bonded to the body on at least its distal portion so that it cannot be displaced from the surface 5 of the body when the body is compressed to fit it into the applicator tube.

The means for withdrawing the indwelling device is, conveniently, a string that extends from the proximal end of the body toward the labia (when in use) so that the user can readily grip it in the same way as the withdrawal string of a tampon. 0 Where an inverting membrane is used as the sample retention means, it will be convenient to use the withdrawal string to secure the centre of the membrane to the distal end of the body. However, other methods of securing the retention means to the body, such as heat or adhesive bonding or physical incorporation, are also envisaged. 5

Where a swab-like element is used as the sample retention means, it need not be highly absorbent and may have a comparatively coarse and open structure - whether fibrous or spongy - so that it will exert a gentle scraping action on the cervix and/or vaginal vault. Indeed, the swab-like sample retention means and o the body may be one and the same physical structure, with the sample retention means comprising the distal surface of the body. Such a combined body and sample retention means might be, for example, a soft resilient pad formed from fine stainless steel wire, as is known in the art and is commercially available.

5 The collected sample may be isolated and handled in a variety of ways. If a separable sample-retention membrane is not employed, the distal end of the body may be smeared onto a microscope slide or rinsed in a container of preservative, in the conventional manner for Pap Smears. The body of the device may then be disposed of like a tampon. If an everting sample retention membrane is o employed, it can be attached to the distal end of the body at a single point and can be readily severed from the body at the point of attachment and dropped into a jar of fixative solution without being handled in any other way. A separable swab-like sample retention means can be treated similarly, either being wiped onto a slide or severed from the body and dropped into fixative solution.

However, a number of alternatives are possible where a filter-like sample- 5 retention semi-permeable membrane is used. After separation from the body, the membrane can be laid onto a slide or a porous transfer plate (with or without preliminary rinsing) with the sample side against the slide or plate. Transfer of the sample (filtrate) from the membrane onto the slide can be assisted by the application of mechanical, hydraulic or pneumatic pressure from a hand-operated o syringe-like device or by the use of a semi-automated machine. If the membranous sample retention means cannot be processed immediately in this manner, the user can place the membrane flat on moist sterile fixative pad which is then covered and hermetically sealed for transfer to a processing laboratory. The preserved membrane sample may then be used in a semi-automated 5 machine that transfers the sample filtrate material onto a microscope slide in a similar manner as samples are transferred from ThinPrep® filter paper to slides. This avoids the need to transfer the sample material to a dilute solution and then re-concentrate it by filtration. However, as already noted, the sample retention means may - if desired - be dropped into or rinsed out in a fixative solution in the o conventional manner now employed in ThinPrep® analysis.

From another aspect, the invention comprises a method of taking samples from the vaginal introitus which is characterised by fully inserting a soft and pliable swab-like sampling device into the vagina, leaving the device in place (preferably 5 for a period between a few minutes and a few hours, more preferably for between

15 minutes and three hours and, most preferably, for a period of between 30 and 90 minutes), removing the device, and extracting a sample of intra-vaginal material from the device. The method may include the procedures for the removal of the sample retention means, its fixing and/or preservation and the 0 processing of the sample material as outlined above. DESCRIPTION OF EXAMPLES

Having broadly portrayed the nature of the present invention, particular examples will now be described by way of illustration only. In the following description, reference will be made to the accompanying drawings in which:

5

Figure 1 is a diagrammatic representation of the sampling system that forms the first example of the invention; parts (a) to (f) of this Figure showing successive stages in the collection and processing of samples.

Figure 2 is a diagrammatic representation of a sampling device, which forms o the second example of the invention; parts (a) to (e) of this Figure showing successive stages in the collection of samples. Figure 3 is a diagrammatic representation of a sampling device, which forms the third example of the invention; parts (a) to (f) of this Figure showing successive stages in the collection of samples. 5 Figure 4 is a diagrammatic representation of a sampling device, which forms the fourth example of the invention; parts (a) and (b) of this Figure showing two stages in the collection of samples. Figure 5 is a diagrammatic representation of a sampling device, which forms the fifth example of the invention; parts (a) to (c) of this Figure o showing three stages in the collection of samples

Figure 6 is a diagrammatic representation of a sampling device, which forms the sixth example of the invention.

In the sample collection means of the first example, the body and the sample 5 retention means are integral in that the sample retention means comprises the formamenous surface 100 of a soft and resilient swab-like body 102 which can be formed from synthetic sponge material, a soft pad of stainless steel wire, and/or from cellulose and polyester fibres - all of which are known in the art. When uncompressed, body 102 has a generally spherical shape of 15 to 20mm in 0 diameter so that it will be retained in the vaginal vault 104 (Figure 1 (b). It should be considerably softer than a tampon so that it can be readily deformed as it is withdrawn. In this case, the withdrawal means is a string 106 secured to the body. In this example, it is preferable to use an applicator 108 comprising an open ended tube 110, a piston rod 111 and an elongate piston 112 which is slotted to accommodate the withdrawal string 106, as shown in Figure 1(a) Tube 110 is 5 preferably of about 10 mm in diameter so that it will enter and pass along the vaginal canal 114 [Figure 1 (b)] comfortably, while not making it difficult to load body 102 therein

After self-insertion using applicator 108, swab-like body 102 is retained within o vaginal vault 104 for at least 30 minutes, preferably some hours, while the user goes about her normal duties It is then withdrawn using string 106 and applied by the user to at least one microscope slide 1 16 [Figure 1 (c)] to form one or more Pap-smears Immediately after smearing the sample on slιde(s) 116, a fixative solution is applied from an eyedropper 118 and the slιde(s) are packaged and 5 sent to a pathology laboratory for professional microscopic assessment The microscope is indicated diagrammatically at 120 in Figure 1(f)

Alternative to, or in addition to, the preparation of slιde(s) 116, swab 102 can be dropped into a fixative solution 122 in a container 124 [Figure 1 (c)] Or, device 0 100 can simply be dangled from string 106 into fixative solution 122 and jiggled about to dislodge and wash off the sample material into solution 122 Container 124 is then sealed, packaged and sent to a pathology laboratory that has a ThinPrep machine for assessment The ThinPrep machine 126 filters the fixative solution 122 [Figure 1 (d)] and transfers the filtrate to a microscope slide 128 5 [Figure 1(e)] that is then assessed under microscope 120 by a pathologist

The device 200 of the second example comprises a body 202 that is shaped and proportioned like a tampon but is not made of adsorbent material Body 202 is preferably made from closed-cell plastic sponge that is soft to touch but not 0 readily deformable, again, like a tampon It has a cup-like distal end 203 that accommodates a swab-like sample retention means 204 which can be formed like the swab 102 of the first example, or as in the present example, can be formed from dry compressed absorbent material, such as cellulose, which expands considerably when wet A thin protective skirt-like membrane 206 that is lubricated and substantially impermeable is located between swab 204 and body 202, the swab 204, membrane 206 and body 202 being held together by a withdrawal string 208 that passes through the centre of all components and 5 extends from the bottom of body 202

As shipped [Figure 2(a)], the proximal portion 207 of sample retention means 204 is shaped to fit snugly a cup-like recess formed in the upper (distal) end of body 202 capturing the centre of membrane 206 which is arranged to extend in the o proximal direction Preferably the outer surface of membrane 206 is lubricated to assist insertion of the device The proximal portion of the withdrawal string is shown folded at 208a The entire device is enclosed in a hygienic and sterile package 209

5 After removal from package 209 and self-insertion using a finger or an applicator as preferred, sample retention means 204 is located in the vaginal vault near the cervix (not shown), the proximal entry to the vaginal vault (not shown) being effectively sealed by membrane 206 and body 202 As moisture and sample material is collected by the swab-like retention means 204, it expands somewhat 0 as shown in Figure 2(b) Upon withdrawal using string 208 [Figure 2(c)], membrane 204 is everted by rolling on the vaginal wall to cover retention means 204 [Figure 2(d)] and to reduce the loss of sample material on the vaginal wall

The user then arranges membrane 206 to uncover retention means 204 and 5 either smears a slide 210 [Figure 2(e)] or severs the string 208 at a point between body 202 and means 204 [Figure 2(d)] and drops swab 204 (without membrane 206) into container 212 of fixative [Figure 2(e)] Slide 210 and/or container 212 are then processed in the same manner as for the first example

o The device 300 of the third example [Figure 3] comprises a body 302 of absorbent material such as a blend of cotton and polyester fibres, body 302 being manufactured in a dry and compressed state Preferably, the distal portion 302a of the body 302 is highly absorbent while the proximal portion 302b is much less absorbent. This may be achieved by varying the composition of the material, by varying the degree of compression or by employing two different materials.

Preferably, the proximal end 302c is treated to be impervious to water, as by dipping it in a suitable polymer or the like.

5

Semi-permeable membrane 304 serves as the sample collection means and is fitted over body 302 so as to completely cover it, excepting for its bottom face. The centre of membrane 304 can be bonded to the distal end of a withdrawal string 308 that passes right through body 302, as shown; or, the centre of o membrane 304 can be bonded to the centre of the distal end of body 302 by adhesive, ultrasonic welding or heat. Membrane 304 may be formed from short bonded cellulose, polyethylene and/or polypropylene fibres in the manner well known in the filter paper art so that cellular and bacterial material will be retained thereon while water is enabled to pass there-through. While membrane 304 may 5 be lubricated to make insertion more comfortable, it is preferable to avoid lubricants (especially those which are greasy) and to rely upon the composition and texture of the material for comfortable insertion.

After insertion [Figure 3(b)], the distal portion 302a of body 302 draws in moisture 0 from the vaginal vault through membrane 304 so that portion 302a expands relative to lower portion 302b. The flow of moisture into the distal portion 302b of body 302 is inhibited by the higher density of that portion and by the impermeable layer 302c. Accordingly, substantially all moisture taken up by the body 302 is imbibed through the central and distal portion of membrane 304. This portion of 5 membrane 304 thus collects tissue and bacterial cells on its external surface.

Upon withdrawal of the device, membrane 304 is everted upon itself [as shown in Figure 3(c)], so that all the sample material and filtrate that has been retained on its external face is now protected on the inside thereof. Membrane 304 is then o separated from attachment area 306 by cutting or tearing [Figure 3(d)] and placed in a sample container (not shown) as in the previous examples, or it is placed upon a slide or transfer plate 310 [Figure 3(e)] so that the filtrate is presented to plate 310. Transfer of the filtrate from membrane 304 may be assisted by air pressure applied, for example, by the use of a simple pump 312. This technique is known and employed in the ThinPrep® system.

The fourth example is illustrated in Figure 4 and comprises a device 400 having 5 a highly adsorbent elongate body 402 which has the shape and size of a tampon and which is formed from an open-cell polymeric foam, or from cellulose and polyester fibres like a tampon. The distal face of body 402 is loosely covered with a semi-permeable filter membrane 404 while the rest of body 402 - including the entire proximal portion 403 - is covered by an impermeable plastic bio-compatible o membrane 406 that may be a coating on body 402, or a separate container-like covering, which extends to the periphery of filter membrane 404 to which it is bonded. A skirt-like membrane 408 is bonded to impermeable membrane 406 at or near the periphery of filter membrane 404. Finally, a withdrawal string 410 is affixed to body 402 and extends through the proximal face 412 of impermeable 5 membrane 406.

Figure 4(a) shows device 400 as it might appear when inserted like a tampon in a vagina 420 so that its distal end with filter membrane 404 is located in the vaginal vault 422 in close proximity to the cervix 424. The proximal portion 403 of body 0 402 and the skirt 408 then effectively close off the vaginal canal 426 and skirt

408 lines most if not all of the canal. Figure 4(b) shows the device 400 as it might appear just after removal from vagina 420. Skirt 408 has been inverted over filter membrane 404, protecting the sample material collected thereon. Moreover, by peeling off the walls of vaginal canal 426 as device 400 is being 5 withdrawn, the use of skirt 408 makes the withdrawal process - as well as the insertion process - comfortable for the user. Skirt 408 also protects the proximal portion 403 of body 402 from contact with vaginal fluids so that it is not unpleasant to grasp or touch.

0 It will be appreciated that the use of impermeable membrane 406 over all of the body which is not covered by filter membrane 404 ensures that all moisture imbibed by body 400 is drawn from the vaginal vault 422 in close proximity to the cervix and all cellular matter entrained therewith is retained on filter membrane 404. To separate filter membrane 404 from the rest of device 400, the user grasps the distal portion 403 of body 400 in one hand and the free end of inverted skirt 408 in the other and pulls to detach skirt 408 and filter membrane filter membrane 404 from body 402 and impermeable membrane 406. Filter 5 membrane 404 can then be cut free from skirt 408 and processed in the manner described in the previous examples.

The fifth example, shown in Figures 5 (a) to (c) can be regarded as a variant of the device of the fourth example that is applicable where the use of an applicator 0 tube is not objectionable. In this case, as shown in Figure 5(a), the device 500 has a body 502 that is of spherical or oblate shape and is formed from open-cell water-imbibing plastic foam that is readily compressible. The proximal portion of body 502 is covered with a water-impermeable coating 502a while its distal portion is covered with a semi-permeable filter-like membrane 502b of the type 5 previously described. A protective skirt-like membrane 504 surrounds body 500 and is conveniently attached to the junction between proximal coating 502a and distal membrane 502b on body 500.

In order to use device 500, it is compressed and fed into an applicator tube 506. o The compression of the body 502 forces air therefrom through semi-permeable membrane 502b. Figure 5(b) shows the device loaded in tube 506. The device is then inserted into the vaginal vault (not shown) using applicator 506, allowing the foam body 502 to expand and to apply a negative pressure on the inside or proximal face of the filter membrane to suck fluid from the vault into the body. 5 Though the pressure in body 502 will be quickly equalised with that of in the vaginal vault, fluid will continue to be imbibed by the body through capillary attraction. As before, cellular material will be collected on the surface of the semi- permeable membrane. Finally, after a suitable period, the device is removed using withdrawal string 508, causing skirt 504 to be inverted over membrane 0 502b as shown in Figure 5(c). The collected sample material can now be readily rinsed off membrane 502b by squeezing body 502 a few times while membrane 502b is immersed in a fixative solution (not shown). The sixth and final example is shown in Figure 6. In this example, the device 600 comprises a swab-like member 602 mounted on the distal end of an applicator rod 604. Member 602 consists of an adsorbent body 606 moulded onto the distal end of applicator 604, and a layer of semi-permeable material 608 coated 5 on the exposed surface of body 606. As in previous examples, it is preferable to employ a guard skirt 610 around the proximal peripheral edge of body 606.

The device of the sixth example is inserted into the vagina until the cervix or vaginal vault is felt and left in place for a few minutes to allow body 502 to imbibe o fluid from the vault through membrane for coating 608. The device is then withdrawn, causing skirt 610 to be protectively inverted over loaded coating 608.

It will be appreciated from the above-described examples that the body of the sample collection means serves one or more functions: 5 • it can act as a tampon-like indwelling applicator by which the sample retention means is inserted by the user,

• it can serve to locate and retain the sample retention means in the vault of the vagina and in close proximity to the cervix, and/or

• it can act as a pump that draws moisture through the sample retention means 0 by both hydrostatic and capillary pressure.

Similarly, it will be appreciated that the membrane-like sample retention means can also have multiple functions:

• it filters out and thus concentrates cellular material onto a surface from which 5 such material can be readily transferred, and

• it can invert upon withdrawal, to prevent the sample material which has been collected from rubbing off on the vaginal wall.

Similarly, it will be appreciated that the use of an everting protective membrane o that does not serve as the sample retention means also has a number of functions:

• it can lubricate insertion of the device, • it can effectively seal-off the vaginal vault during sample collection so that the liquid from the vault cannot by-pass the sample-retention means,

• it can facilitate comfortable withdrawal of the device by peeling off the vagina wail, • it can serve as a sterile package or container for the device as shipped, and

• it can protect the user's fingers from contact with vaginal fluids during insertion, removal and subsequent handling of the device.

While a number of examples have been described which fulfil the objectives of the invention, it will be appreciated that many others are possible, and that many variants of the examples are possible, without departing from the scope of the invention as defined in the following claims.

Claims

1 Sampling means adapted for insertion into and temporary retention within the vaginal introitus for the purpose of obtaining biological samples therefrom, the sampling means comprising: 5 a body of soft bio-compatible material having a shape and configuration adapted to retain it within the vaginal introitus, said body having an external distal surface, a proximal portion supporting said surface and sides, sample retention means forming said external distal surface of the body or affixed thereto, said sample retention means being adapted engage and retain o vaginal mucosa and/or cellular material contained therein, and means attached to the body for withdrawing said body together with said sample retention means from the vagina to recover biological samples retained by said sample retention means.

5 2 Sampling means adapted for insertion into the vaginal introitus for obtaining biological samples therefrom, said means comprising: a body of biocompatible material, said body having an external distal surface, a proximal portion supporting said surface and sides, sample retention means forming said external distal surface of the body or o affixed thereto, said sample retention means being adapted engage and retain vaginal mucosa and/or cellular material contained therein, and an elongate applicator attached to said proximal portion of the body for introducing said body into the vaginal introitus and for withdrawing said body from the vaginal introitus. 5

3 Sampling means according to claim 1 or 2 wherein, said body is formed from water-imbibing and adsorbent material, and said sample retention means comprises a semi-permeable membrane that is permeable to water but adapted to retain cellular material thereon, 0 so that at least part of the aqueous fluid imbibed by said body material, when the sampling means is retained in the vaginal introitus is drawn through said membrane and said distal surface. 4 Sampling means according to claim 1 or 2 wherein: the sample retention means comprises a membrane that normally rests upon and covers at least part of said distal surface of the body, said membrane has a central portion and a peripheral edge, and 5 the membrane is attached to the body by its said central portion so that its said peripheral edge extends laterally beyond the sides of the body, so that, when the body is withdrawn from the vaginal introitus using said withdrawing means, said membrane will be inverted by contact between the introitus and said peripheral edge and so that sample material on said sample 0 retention means will be protected from contact with the vaginal introitus by being substantially enclosed within the inverted membrane.

5 Sampling means according to claim 3 wherein, said body is formed from water-imbibing and adsorbent material, and 5 said membrane of the sample retention means is semi-permeable, being permeable to water but adapted to retain cellular material thereon, so that at least part of the aqueous fluid imbibed by said body material, when the sampling means is retained in the vaginal introitus is drawn through said membrane and said distal surface. 0

6 Sampling means according to any one of claims 3 to 5 wherein, said means for withdrawing the body comprises a string extending from the proximal portion of the body, and said string extends through said body and secures the semi-permeable 5 membrane to said body.

7 Sampling means according to any preceding claim wherein: at least portion of the surface of the body, other than said distal surface, is covered by a water-impen/ious layer that prevents moisture entering said portion o of the surface of the body.

8 Sampling means according to any preceding claim wherein: the body is formed from a soft open-cell plastic foam material, and substantially the entire surface of the body, other than said distal surface, is covered by an air and moisture-impervious, so that compression of the body will expel air from said body and so that release of the compressed body within the vagina will cause vaginal fluid to be sucked into the body through said semi-permeable membrane.

9 Sampling means according to any preceding claim wherein, a skirt-like membrane is attached to the body at a point proximal to the sample retention means, so that, when the body is withdrawn from the vaginal introitus, said skirt-like membrane will be inverted to enclose the sample retention means and said distal surface of the body to protect them against contact with the walls of the vaginal introitus.

10 A method of sampling the vaginal introitus comprising the steps of: inserting into the introitus a water adsorbent body having a semi-permeable membrane covering a distal surface of the body, allowing fluid from the introitus to be imbibed by said body through said membrane so that cellular material contained in the fluid is retained by the membrane, and withdrawing said body with said membrane from the introitus to recover said membrane and any cellular material retained thereby.

11 A method according to claim 10 wherein the membrane is attached to the body by a central portion of the membrane only so that, as the body and membrane are withdrawn, the membrane is inverted by contact with the sides of the vaginal introitus and the cellular material thereon is thereby protected from contact with the walls of the introitus.

12 A method of according to claim 10 or 11 including the steps of: inserting into the introitus together with said body a skirt-like membrane attached to the body proximally of said distal surface, and withdrawing said body and said skirt-like membrane from the introitus to cause said membrane to invert and to cover said body and protect its distal surface from contact with at least portion of the walls of the introitus

5 13 A method of sampling the vaginal introitus comprising the steps of inserting into the introitus sample retention means comprising a water permeable sheet-like membrane that is attached to and supported by the distal end of a soft porous body, said membrane having a distal surface adapted to retain tissue cells and microbiological material contained in cervical and vaginal o mucosa, leaving the body and membrane in place for at least 30 minutes, withdrawing said body and sample retention means from the introitus so that the membrane is inverted upon itself thereby shielding material retained on its distal surface from contact with the walls of the introitus during withdrawal 5

14 A method according to any one of claims 10 to13 which includes the following steps after withdrawal of the body and membrane from the introitus detaching the membrane from the body, o placing the membrane into a container of fixative solution, filtering said solution to concentrate particulate material therein, and subjecting the concentrated particulate material to microscopic analysis

15 A method according to claim 10 to 13 which includes the following steps 5 after withdrawal of the body and membrane from the introitus detaching the membrane from the body, laying or smearing the membrane on a microscope slide to transfer portion of the sample material to the slide, and subjecting the material transferred to the slide to microscopic analysis 0

16 A method according to any one of claims 10 to 13 which includes the following steps after withdrawal of the body and membrane from the introitus detaching the membrane from the body, laying the membrane on a pad containing fixative liquid to fix the microbiological and tissue particles therein, hermetically sealing the membrane in a container, 5 shipping said container and membrane for laboratory analysis.

17 A method according to any one of claims 10 to 16 which includes the step of compressing said body to expel air therefrom before placing it in the vagina and then allowing the body to expand to cause vaginal fluid to be sucked l o into the body through said semi-permeable membrane.