WO2016145501A1

WO2016145501A1 - Devices, kit and method for screening, diagnosing and monitoring the evolution of a disease, used for prognosis and theranostics

Info

Publication number: WO2016145501A1
Application number: PCT/BR2016/050053
Authority: WO
Inventors: Daniela Bauman CORNÉLIO; Caroline Brunetto DE FARIAS
Original assignee: Ziel Biosciências Pesquisa, Desenvolvimento E Diagnóstico Ltda.
Priority date: 2015-03-16
Filing date: 2016-03-14
Publication date: 2016-09-22
Also published as: BR102015005720A2; BR102015005720B1

Abstract

The present invention describes devices that form a kit that can be used for screening, diagnosing and monitoring the evolution of diseases such as cervical diseases, used in prognosis and theranostics. In specific, the present invention comprises devices and methods for monitoring the physiological state of the cervix. The present invention pertains to the fields of medical science and instruments for medical examinations and diagnostic methods.

Description

Patent Invention Descriptive Report

SCREENING, DIAGNOSTIC, PATHOLOGY DEVELOPMENT, PROGNOSTIC AND DEVELOPMENT MONITORING DEVICES, KIT AND PROCESSES

THERANOSTICS

Field of the Invention

The present invention describes devices that make up an apparatus and a kit that can be used in the screening, diagnosis, follow-up, prognosis and teranostic of conditions such as cervical disorders. The present invention is in the fields of medical science, medical examination instruments and diagnostic methods.

Background of the Invention

[0002] UTERINE CANCER SCREENING

Cervical cancer is the second most common cancer in women in Brazil and in many parts of the world, especially in developing countries. In our country affects about 20 thousand women per year, and a quarter of these die due to the disease. Cervical cancer is one of the few tumors that can be prevented; When diagnosed in the early stages, it can achieve 100% healing. Because of this, there is a global effort to discover new methods to improve early screening and diagnosis.

[0004] The incidence of cervical cancer has decreased dramatically in recent decades following the introduction of screening tests. The oldest method that remains the main tool for detecting precursor lesions and cervical cancer is the Pap smear. This consists of introducing a speculum into the vagina, obtaining a cervical sample collected with a spatula and brush, depositing this material on a glass slide and fixation, with subsequent microscopic analysis in the laboratory. The exam is usually collected by a doctor or other healthcare professional. empowered. Cervical cytology depends on proper sample collection and skillful interpretation of cell morphology under a microscope. Both activities require extensive training and ongoing quality assurance.

[0005] The World Health Organization (WHO) advocates that screening for cervical cancer should reach at least 80% coverage for the target population. Unfortunately in Brazil, only 20% of women have had the exam at some time in their lives, for reasons that include poor access to health services, discomfort in gynecological examination, cultural or religious issues and misinformation. Even in high-income countries, where screening programs are widely available, there is low coverage and declining participation rates. A recognized barrier in these cases is the need to undergo a pelvic exam, which some women find uncomfortable, invasive or unacceptable for emotional or cultural reasons.

In addition to the difficulties of access and acceptance of the examination by women, there are other problems. Among the Pap smears that are performed, many are considered unsatisfactory due to errors in collection (collection of material from the vaginal wall and not the cervix), errors in fixation and interpretation of results. An analysis by the Rio Grande do Sul Health Department showed alarming levels of poorly collected tests, reaching 80% in some regions.

Even when performed technically appropriately, Pap smears have limitations, particularly with respect to false-negative screening results (SAFAEIAN et al., 2007). That is, a woman may have a precursor lesion or even cervical cancer, and the exam may show normal results. Studies show that a single Pap smear is only 50% sensitive for detecting high-grade lesions or invasive carcinoma (FRASER et al., 2005).

In addition, up to 10% of Pap smears are classified as ASCUS (atypical squamous cells of undetermined significance), or that is, it is not possible to clearly categorize normal examination, moderate or severe injury, or tumor. However, experience shows that up to 10% of this ASCUS population has high-grade lesions that may go unnoticed (MANOS et al., 1999). On the other hand, a significant proportion of women, especially after menopause, have cytopathological exams classified as ASCUS, and do not have neoplastic lesions. This may be due to lack of estrogen, as there is no complete maturation or glycogenation of the epithelium, which becomes thin, atrophic and friable. Moreover, in the postmenopausal cervix the size of the cervix is reduced and the squamous-columnar junction (where neoplastic lesions originate) migrates into the endocervical canal and is often inaccessible to visual examination. For this group of women, prior topical estrogen treatment is often required to improve epithelial trophism, promote squamous-columnar junction ectopia, and thus not impair screening and diagnostic examination.

An alternative method for improving the diagnostic performance of cervical cytology was the development of liquid based cytology (CBL). Today, many screening programs are already using liquid-based cytology rather than conventional Pap smears. Through CBL, samples are collected using a small plastic brush and stored in a liquid transport medium. Glass slides are prepared from the cells in this transport medium in the laboratory. This eliminates errors in the fixation of the material by the sample collector, and the visualization of cells is facilitated, allowing a better interpretation of the slides.

Further advances in cervical cancer screening have been achieved following the discovery of human papillomavirus (HPV) as the main etiological agent, as well as several molecular indicators of neoplastic injury, such as GRPR, p16INK4a, KI67, among others. The gastrin-releasing peptide receptor (GRPR) demonstrates overexpression in dysplasias and cervical cancer, and seems to be implicated in the carcinogenic process of these tumors. In addition, it demonstrates high accuracy for ASCUS classified lesions. P16INK4a is considered a marker for HPV oncogenic activities in cervical cells and its overexpression is well established in CIN and invasive cancer through many studies. Ki-67 is an antigen that identifies proliferating cells and is expressed at all stages of the cell cycle.

HPV DNA has been shown to be present in more than 95% of cervical carcinomas. It is now widely accepted that HPV tests are used to screen women with dubious cytology and to predict recurrence after treatment for precancerous lesions. Data from randomized trials have consistently shown that women with negative HPV tests have a lower risk of developing CIN 3 and invasive cancer compared with women with a normal Pap smear. Thus, there is already a recommendation to modify the secondary cervical cancer prevention policy and use an HPV test as the primary screening test, either alone or in combination with the Pap smear. The HPV test has the advantage that it can be performed by a vagina sample by the women themselves, and may provide the opportunity for screening for those women reluctant to pelvic exams.

[0012] EXAMINATION BY AUTO COLLECTION

An alternative that has been employed to assist in cervical screening, both in the developed world and in developing countries, is to obtain self-collecting cervical material. Auto collection can overcome two major problems inherent in current tracking strategies: cost and coverage. It is difficult to maintain the large number of clinics needed for mass population screening, especially in resource-constrained regions. Studies have shown that self-collection is a practical and effective way to obtain cervical cell samples. womb, being widely acceptable by women and eliminates the cost of a visit to a doctor.

In the last decade numerous studies have been conducted in a wide variety of countries and ethnic groups, demonstrating that self-collection is well accepted by women and in some groups may be preferable to cervical sampling obtained from the speculum. Virtually all acceptability measures, including pain, embarrassment, and anxiety, favored the self-collection approach. In addition, there appear to be no specific cultural or religious barriers to self-sampling. The self-collection approach allows women to obtain samples with privacy and comfort, with the added benefit of choosing the time and place of sampling.

[0015] The most commonly used devices for self-collection are cotton swabs, which can be made of spun polyester fiber or treated cotton on a plastic rod. Another device used is a small brush-like or Christmas tree-shaped nylon brush. Women may be reluctant to wear devices that look uncomfortable or resemble medical instruments. Even simple cotton swabs may be rejected by some women. Hence the need to develop an easy-to-use, comfortable and safe self-collection device, thus promoting greater tracking compliance and saving costs in the long run.

AUTO COLLECTION SENSITIVITY AND SPECIFICITY

Studies have already shown that self-collected samples capture more cells compared to samples taken from traditional sampling. In a recent meta-analysis that evaluated 36 studies with 154,000 patients, HPV self-collection tests averaged 76% of CIN 2 or more severe lesions and 84% of CIN 3 or more severe lesions. Specificity to exclude CIN 2 or CIN 3 and more severe lesions was 86 and 87%, respectively. Sensitivity of auto collection was lower than the collection by professional (0.88), as well as the specificity (0.96). The lower sensitivity of 11% using self versus professional collection led the authors to recommend the latter, with self-collection being the option for those women who do not participate in screening programs (ARBYN, M., 2014). However, this analysis was based on a heterogeneity of effects considering the different methods used. When PCR-based HPV tests were used, the relative sensitivity was similar to that collected by professional in all cases, and the relative specificity was similar in 6 of 7 tests used, suggesting that a test with higher analytical sensitivity would be necessary to ensure similar accuracy to professional collection.

Due to the fact that clinically relevant lesions originating from the squamous-columnar junction are collected directly during the specular examination, it is expected that the viral load will be higher compared to the self-collecting, which occurs indirectly. This has already been confirmed by Belinson et al. (2010), who demonstrated that the average signal strength of the Hybrid Capture 2 test decreased as samples were collected directly from the endocervix (688 RLU), to the upper vaginal portion (1 18 RLU) and lower (51 RLU). In this study, as expected, self-collected samples demonstrated an intermediate viral load (273 RLU). Thus, a collection device that allows self-collection of material closer to the squamous-columnar junction has the potential to offer tracking performance comparable to professional collection.

[0019] In the search for the state of the art in scientific and patent literature, some documents dealing with the subject were found below.

[0020] There are numerous devices and devices in the market today for auto-collecting HPV detection. However, it appears that all available devices and apparatus do not provide the user with the necessary comfort when collecting the sample, besides the fact that there is no cells as with the device disclosed by the present invention.

Examples of commercially available HPV auto-detection detection devices include: Rovers Evalyn Brush (Rovers Medical Devices BV), FLOQSwabs (Copan Flock Technologies SRL), HPV Home Test (Microbiome Ltd), Just form Me self-sampling brush (Preventive Oncology International Inc.), Abbott Multi-Collect Specimen Collection Kit (Abbott Molecular), Digene Female Swab Specimen Collection Kit (Qiagen Corp), Digene Cervical Sampler (Qiagen Corp), Cytobrush Plus classic version (Carefusion, UK). However, none of said commercially available products confer the advantages of the device disclosed in the present invention, which advantages include greater user comfort, greater sample (and therefore cell) availability, ease of use of the device and do not involve injecting fluids into the user's body.

US 200401 16827 A1 discloses a cervical tissue collecting device which is a stem having a bulb-shaped nylon brush end located within a tube. The end of the tube that approaches the cervix during collection contains a thin protective layer. When the device is inserted into the vagina, the cable is pushed so that the brush pierces the shield. The brush exposed on the cervix is manually rotated to collect cervix and endocervix specimens. Subsequently, the brush handle is pulled back into the tube and the device is removed from the vaginal cavity. To evaluate the collected material, remove the brush from the tube again and transfer the material to a glass plate. However, the present method may cause discomfort for the patient, since the brush bristles are aggressive, and the collection depends on the correct handling of the device, since the rotation is manual, which may result in the collection of an inappropriate material. Document BR PI 0713816 discloses a diagnostic kit for conducting a self-test for detection of cervical cancer precursor lesions. The kit comprises a container for storing methanol and a container for storing medical instruments consisting of a bristle-bristled semi-spherical head brush. This is inserted into the cervix to impregnate the bristles with uterine colon cells and then the brush is inserted into the methanol flask to store the sample for further analysis. Thus, the method of collection is not completely effective as there may be contamination with cells from other regions of the vaginal canal, and the range of cervical range is not wide.

US 6475165 B1 discloses a cervical material collection device that can be used by the patient herself. The device consists of a cylindrical cardboard tube that acts as a telescope and stores a retractable sponge. The extended device is inserted into the vaginal cavity until resistance is obtained, and then the sponge holding rod is pushed and rotated by hand. The rod is retracted to return to the cavity of everything before being removed from the vaginal cavity. Subsequently, the sponge is immersed in a tube containing fixative or preservative. Thus, the technique revealed in this document depends on the correct handling of the operator to obtain an adequate collection, since the sponge rotation is manual. Additionally, sample collection is limited due to the small area the sponge reaches.

US 8672861 B2 discloses a device, kit and method for collecting cervical tissue that can be sampled by the patient herself. The device is a cervical sampling brush that has a cylindrical outer shield and a tool that keeps the brush aligned. In addition, the device has a device that, when used, distends the cervix so that the brush comes in contact with the tissue allowing cell adhesion in the bristles. The device is inserted into the vagina in order to enable rotation. times for cell adhesion to occur on the bristles. Before removing the device, the brush is retracted into the protective tube again. In addition, the document discloses a cervical tissue collection kit comprising the previously described device, a container containing cellular preservative and instructions for use. Thus, the device may cause discomfort to the patient at the time of collection, as there is mechanical distension of the cervix by the apparatus. Therefore, despite the strategy of distending the cervix to allow the collection of a wider surface, this technique can bring extreme discomfort to the patient.

WO 2005041751 A2 discloses a collecting funnel used with a testing device. The funnel stores a fluid sample in order to contact the sample with a diagnostic tape. The funnel also has a chamber that stores buffer, so that there is an access to the chamber with the sample, allowing the buffer to pass through the sample and drag it through the tape. However, this device is structured for liquid samples and does not allow storage of these for subsequent analysis.

Thus, from what is clear from the researched literature, no documents were found anticipating or suggesting the teachings of the present invention, so that the solution proposed here has novelty and inventive activity in relation to the state of the art.

Thus, state-of-the-art devices and kits enable the patient to self-collect; however, given the revealed technology, collection may be inaccurate, resulting in an unsatisfactory or uncomfortable sample for the patient.

Summary of the Invention

Thus, the present invention aims to solve the constant problems in the state of the art from a device and devices that make up a kit, enabling the patient to perform the self-examination in order to collect the sample in a simple way. , needs, in adequate quantity and comfortably. In addition, the present invention enables the sample to be stored so that it can be used for a variety of purposes.

In a first object, the present invention provides a collecting device comprising a plunger with a fringed circular shaped spongy material in the distal portion and a housing, so that when the plunger is actuated, the sponge exits the rotational motion.

In another object, the present invention provides a sample receiving device comprising a chamber containing storage solution.

In another object, the present invention provides a medical kit comprising the collecting device and the sample receiving device.

In another object, the present invention features a screening process comprising the following steps:

a) inserting the collecting device as defined in claim 1 into the body cavity;

b) actuating the plunger so that the spongy material exits the housing;

c) retracting the plunger to collect the spongy material; d) remove the collecting device from the body cavity; e) inserting the distal portion of the collecting device into the sample receiving device as defined in claim 2;

f) depressing the plunger of the collecting device; and

g) retract the plunger of the collecting device.

In another object, the present invention provides a diagnostic process in which the screening process is performed.

In another object, the present invention provides a pathology follow-up process in which the screening process is performed sporadically.

In another object, the present invention provides a prognostic process in which the screening process is performed sporadically. In another object, the present invention provides a teranostic process in which therapy for a pathology, physiological condition or damage repair is performed and, in addition, the screening process.

Still, the inventive concept common to all claimed protection contexts is based on the composition of a kit with the mentioned devices that can be used for assessment of the physiological state of the body cavity under examination of the patient.

[0039] These and other objects of the invention will be immediately appreciated by those skilled in the art and companies having an interest in the segment, and will be described in sufficient detail for their reproduction in the following description.

Brief Description of the Figures

In order to better define and clarify the contents of this patent application, the following figures are presented:

[0041] Figure 1 (a, b, c) shows the outer part of the collecting device in its front, side and top views.

Figure 2 (a, b, c) shows the plunger of the collecting device in its front, side and top views.

Figure 3 (a, b, c) shows the distal portion of the collecting device in its front views,

Figure 4 (a, b) shows an embodiment of a silicone cap next to the distal portion of the collecting device in its closed (a) and open (b) positions.

Figure 5 (a, b, c, d) shows side view of an agar / gelatin cap embodiment containing or not an active, closed (a), being dissolved (b) and allowing exteriorization of the part distal from the collecting device. Figure 5c exemplifies anesthetic-containing agar / gelatin outer cap on the distal portion of the collecting device. Figure 5d exemplifies anesthetic-containing internal agar / gelatin buffer in the distal portion of the collecting device. Fig. 6 (a, b) shows an embodiment of a collecting device receiving device for future collection, storage and / or analysis of the collected sample.

Figure 7 shows the cell count in the Neubauer chamber by the Trypan blue exclusion method, considering the collections with common swab, collector containing at its end a 1 cm diameter sponge (small sponge) and collector containing in Its end is a sponge 3 cm in diameter (large sponge).

[0048] Figure 8 shows the sample pellets. A) cells collected with common cotton swab; B) cells obtained with collector containing at its end a 1 cm diameter sponge (small sponge) and C) cells obtained with collector containing at its end a 3 cm diameter sponge (large sponge).

Figure 9 shows conventional cytology and immunocytochemical examinations of GRPR: A) Cells collected with conventional swab and B) Cells collected with large sponge.

[0050] Figure 10 shows a successful liquid based cytology examination from self-collection with an object collecting device object collecting device embodiment of the present invention. A) Cells collected with conventional swab from patient without injury; B) Cells collected with 3 cm in diameter from patient without lesion; C) Cells collected with conventional swab from patient with injury and; D) Cells collected 3 cm in diameter from patient with injury.

Figure 11 shows a representative graph of high risk HPV hybrid capture examinations performed with the collecting device of the present invention and with conventional brushes.

[0052] Figure 12 shows a representative graph of patient tolerability screening for the collecting device of the present invention, compared to collection by speculum practitioner. Figure 13 shows a representative graph of patient preference screening between the collecting device of the present invention and the collection by speculum practitioner.

Detailed Description of the Invention

The present invention discloses devices that can form an effective kit for assessing the physiological condition of a patient's body cavity. More specifically, the present invention may be used in the vaginal cavity to assess the physiological state of the cervix.

In a first object, the present invention features a collecting device comprising a plunger with a fringed circular shaped spongy material in the distal portion and a housing, so that when the plunger is actuated, the sponge exits the rotational motion.

A) inserting the collecting device as defined in claim 1 into the body cavity;

B) actuating the plunger such that the spongy material exits the housing;

C) retracting the plunger to collect the spongy material;

D) removing the collecting device from the body cavity;

E) inserting the distal portion of the collecting device into the sample receiving device as defined in claim 2;

F) pressing the plunger of the collecting device, and

G) retracting the plunger of the collecting device.

In one embodiment, the body cavity is the vaginal cavity. In another object, the present invention provides a diagnostic process in which the screening process is performed.

[0068] In another object, the present invention provides a pathology follow-up process in which the screening process is performed sporadically.

In another object, the present invention provides a prognostic process in which the screening process is performed sporadically.

In another object, the present invention provides a teranostic process in which therapy for a pathology, physiological condition or damage repair is performed and, additionally, the sporadic screening process.

Secreeninq

In the context of the present invention, the term is to be understood as a process of evaluating a physiological condition.

Diagnosis

[0072] In the context of the present invention, the term is to be understood as a process for evaluating a physiological condition in which a clinical picture is concluded.

Prognosis

In the context of the present invention, the term is to be understood as a medical judgment based on a diagnosis and therapeutic possibilities.

Theranostic

In the context of the present invention, the term is to be understood as a diagnosis accompanied by drug and / or cosmetic therapy.

[0075] The devices and kit allow uterine cervix material to be obtained comfortably and safely at the most appropriate time and place for the wearer, overcoming cost and accessibility as well as emotional and religious barriers. The great advantage of the present invention is that through a sample obtained in a single moment, several tests, both for screening for neoplastic lesions and for diagnosing HPV infections or other pathogens of the vaginal tract.

Liquid-based cytology demonstrates superiority to conventional cytology by improving sample quality and reducing reading time, being preferred by cytologists. In addition, surplus material after testing can be stored in a sample bank, which is an important tool for epidemiological and research purposes.

The use of sponge allows greater comfort to the user because it is a softer material than compressed cotton, and the fringe-shaped sponge has the capacity to absorb a larger amount of sample. In the present invention the sponge rotation mechanism is integrated into the collecting device, the user simply activating the plunger, ensuring greater contact with the uterine cervix cells. In addition, as the spongy material remains stored during insertion and removal of the device through the vaginal canal, contamination by non-cervix cells is prevented.

The advantages conferred by the device disclosed in the present invention are numerous: it does not hurt the patient as the distal end is made of soft material, unlike brushes or other sharp devices; It does not present an uncomfortable shape for patients, since it resembles vaginal cream applicators, which are commonly used and well accepted by women; does not contaminate with vaginal wall material as it is protected by an outer cylinder and silicone "cap"; It has the ability to come into contact with the cervix, even if it is in a non-centralized position, as the distal portion reaches an area of 3 cm in diameter; rotation mechanism of the distal portion is accomplished by simple compression of the piston, not depending on rotation by the user, which may lead to collection errors if not performed correctly; It does not involve injection of fluids into the users' bodies, as some devices use, which can cause great discomfort and fear on the part of the users. of users; The amount of sample obtained is much higher than the other devices, since the distal portion has wide area of contact with the cells and the material has high absorption; surface treatment of the distal portion with solution (eg propylene glycol) allows for greater hydrophilicity to the collector (thereby obtaining more cells) and also minimizes / restores damage to the cervix that could be caused by friction of the distal portion sponge.

Example 1. Example of Embodiment of the Invention

The examples shown herein are intended solely to exemplify one of the numerous ways of carrying out the invention, but without limitation, the scope thereof.

The kit consists of a self-collection device and another sample receiving device, which serves to deposit and store the collected material, which can be used to perform immediate immunochromatographic tests and / or to perform laboratory tests as an examination. pathology and molecular analysis.

[0081] Self material collection kit can be used in various body cavities. In this preferred embodiment, examples of use in the vaginal cavity will be described, more specifically for the collection of cervical material. This material can be used for a variety of purposes, such as cytopathological examination (conventional and liquid-based cytology), GRPR rapid test, HPV rapid test, or HPV molecular test, rapid or molecular test for vaginal pathogens such as Chlamydia, Gonorrhea, Candida, Tricomonas, Gardnerella, Syphilis, among others, database for research, identification and storage of data, but not limited to these.

Example I - Collector Device:

The collecting device as exemplified in Figures 1, 2 and 3 consists of a conical thermoplastic polymer tube with 10 cm in length and 1.2 cm in external diameter and 1.1 cm in internal diameter. At The base has a safety barrier composed by two trapezoidal wings with 1.42 cm at the smallest base and 1.46 cm at the largest base. The corners are rounded and have a radius of 0.2 cm. In the distal portion of the applicator there is a 2.75 cm long handle base with an ergonomic polybutadiene surface consisting of eight 1.2 cm radius rings and eight 1.2 cm radius rings respectively. The base may be transfer molded in the manufacturing process. On the inner edges of the distal portion of the applicator there are small polymeric locks with 0.5 cm long, 0.2 cm wide and 0.2 cm high responsible for spring resistance and can be compression molded in the manufacturing process (figure 1 a, front view; figure 1 b, side view; figure 1 c, top view).

Inside the conical tube there is a plunger composed of thermoplastic polymer which has 4 cm in length and radius of 0.75 cm. The plunger supports a metal spring 3 cm long and 0.8 cm in diameter. In the proximal portion of the plunger there is an ergonomic socket 1 cm in diameter, allowing the user to position the index finger for actuating the plunger. Propulsion of the plunger with the spring will find resistance when the spring is compressed by 2 cm, allowing the distal portion of the collecting device to be externalized. After insertion of the applicator into the vagina, the plunger must be triggered a few times to perform the collection (figure 2a, front view; figure 2b, side view; figure 2c, top view).

The distal portion of the plunger is formed by a 0.5 cm radius dome and eight radial fringes each, 1 cm long and 0.5 cm wide, fixed over two male-female embedded polymer bases. with helical tear for contact. This is produced by stamping polyurethane. When actuated by plunger and spring, the distal portion is projected 2 cm from the collecting device and allows opening and rotation of the fringes. The polyurethane memory allows the distal portion to retract from the retracting the plunger and encapsulating the distal portion in the applicator (Fig. 3a, front view; Fig. 3b, side view; Fig. 3c, top view).

At the distal end is attached a 0.4 cm high conical cap in both flexible silicone material (Figures 4a and 4b) and active-containing agar / gelatin (Figures 5a, 5b and 5c). The lid can also be realized as a 0.3 cm high internal plug (figure 5d). In all alternatives, the lid has the function of preserving sponge integrity, sponge protection from contamination with vagina material, as well as comfort at the time of device introduction due to its rounded and soft shape. In the silicone cap option, when the plunger is actuated, the plunger is easily detached from the distal portion, allowing the sponge to be externalized and remaining attached to the collecting device through a handle. In the agar / gelatin cap option, it may contain actives such as anesthetics, humectants, scars, which upon contact with the inside of the vagina dissolve, releasing the active. By actuating the plunger, this dissolving lid easily allows the sponge to be externalized. In addition, the released asset allows for greater comfort at the time of collection. The remnant of this last cap is completely absorbed by the body, and the active has a lasting and localized effect.

In a preferred embodiment anesthetic may be used on the collector lid to provide more comfort and less pain at the time of collection; a topical estrogen kit can be provided to improve cervical trophism prior to collection (important for women with atrophy, especially after menopause); a healing medication kit can be provided after collection to restore any damage married by collection; In the sponge itself there may be the addition of any of these actives for theranostic, either anesthetic, emollient, healing, etc.

Example I - Sample Receiver Device

The sample receiving device, as exemplified in Figures 6a and 6b, consists of a storage and transport device of the sample containing a 1.5 cm radius and 3 cm deep receiving cylinder coupled to a sealed and capped platform for immunochromatographic testing (rapid tests), both molded from thermoplastic polymer. Inside this receptor cylinder there is a suitable liquid medium for cell preservation, compatible with the performance of several tests, including cytological and molecular tests, allowing the preservation of the sample for a certain time. By means of an internal flooding system, a 0.02 cm diameter circular hole driven by buttons external to the receiving cylinder, the liquid reaches the platform reagent strips. The upper portion has a socket for the collecting device. To store the sample, the user breaks the lid seal, opens the lid, fits the collecting device, tightens the plunger a few times, removes the cylinder and closes the lid. The cylinder side knob can be operated for quick test initialization.

Example 2. Method Comparison and Preliminary Testing

Several experiments have been performed with the aim of performing comparative tests to demonstrate the advantages of the present invention in relation to the state of the art.

Thus, in a first test, a common cotton swab was used, a collector containing at its end a sponge of approximately 1 cm in diameter and a collector containing at its end a sponge of 3 cm in diameter. Both collectors were steam sterilized at 121 ° C.

To collect the cervical smear, with the women in the position of gynecological examination, a vaginal speculum was used that allowed the direct visualization of the cervix. The material was obtained with the three types of collectors, performing circular movements around the cervix. After collection, all collectors were inserted into a vial containing a transport liquid capable of keeping the cells viable for further analysis.

Still, the collectors were washed with 10mL of saline. The total cellular solution (saline and transport medium) was placed in a 15 mL conical tube. From each of the solutions, an aliquot of 10 Âµl was analyzed in a Neubauer chamber under an inversion microscope (10X magnification), allowing visualization of cell morphology and counting.

In all analyzed cases more cells were obtained using the sponge collectors. In addition, the size of the sponge also interfered with the amount of cells, ie the larger the sponge area, the larger the amount of cells, as illustrated in figure 7.

Following microscope analysis, the solutions were centrifuged for 5 minutes at 3000 rpm and the amount of cells can also be visualized according to the size of the respective pellet formed (Figure 8). In all cases analyzed, larger pellets were obtained using the sponge collectors compared to the cotton swab. In addition, there was a direct proportion between the size of the sponge and the size of the formed pellet, confirming a greater obtaining of material with the sponge of 3 cm in diameter.

In a second experiment, cervical samples were obtained by self-collection using the collecting device of the present invention and cotton swab.

Samples were evaluated by cytology and immunocytochemistry method. After centrifugation for 5 min at 3000 rpm, the medium was discarded and the cells were fixed in 70% alcohol for slide preparation. Hematoxylin / eosin (HE) and anti-GRPR antibodies were used. As shown in Figure 9, both HE and immunocytochemistry techniques could be successfully performed through self-collection. In addition, it was A larger number of cells obtained with the collector of the present invention than the swab is shown.

In a third experiment, samples were collected with the collecting device of the present invention and used for liquid based cytology analysis. Generally for this technique an alcohol based cell fixing solution is used. In the present experiment, however, a buffer solution compatible with immunochromatographic tests was used. As shown in figure 10, the technique can be successfully performed, and cytological diagnosis can be performed on both normal and neoplastic lesions by this innovative approach.

[0098] In a fourth experiment, cervical samples were obtained with the auto-collector device of the present invention and also cytobrush brush, the latter by self-collection of the vagina or direct collection of the cervix by a medical professional. Samples were analyzed by the HPV Hybrid Capture 2 hybrid capture method, which identifies the presence of high or low risk HPV. According to the graph in figure 1 a and b, in the different collection methods it was possible to detect the presence of HPV, but the viral load varied according to the method employed. Confirming findings already described in the literature, the signaling was superior when the collection was made directly from the cervical canal by the physician compared to the self-collection with the collecting device of the present invention. Similarly, self-collection with the device using the collecting device of the present invention showed higher signaling than vaginal brush sampling.

All patients who self-collected with the collecting device of the present invention and conventional speculum collection answered a questionnaire. Regarding tolerability, half of the patients considered the speculum examination uncomfortable, while 90% considered the self-collection well tolerated, as shown in the graph in figure 12. When asked about the preference between the two methods, the vast majority (90%) of the patients preferred self-collection with the collecting device of the present invention over speculum examination, as shown in the graph in figure 13.

[0100] In another experiment, plugs were prepared for the outer part of the collecting device using 3 parts gelatin for one part 2% lidocaine anesthetic solution without vasoconstrictor (Figure 4f). After adding the anesthetic solution to the gelatin powder, the mixture was heated in a water bath until the gelatin completely dissolved, forming a uniform solution. The solution was placed in circular containers 1 cm in diameter and 0.3 cm high until it hardened. Subsequently, the plugs were removed from the molds and inserted into the distal portion of the collecting device. After 24 hours total hardening of the plugs was observed. Sensitivity and dissolution tests of the plug were performed. A small fragment of the gelatin and anesthetic preparation was placed over the tongue. Within 20 seconds the compound began to dissolve, with complete dissolution within 60 seconds. The anesthetic effect was perceived as early as 20 seconds, with tingling and decreased local sensitivity. This experiment was repeated weekly from the same batch, and after 3 weeks it was observed that the initial properties were maintained. Subsequently, it preceded the tests in the vaginal cavity. A collecting device containing gelatin plug and anesthetic was inserted into the vaginal cavity. The patient was instructed to wait 60 seconds until the plunger triggered. After 60 seconds, there was no resistance of the plug to the activation of the plunger, being possible to self-collect cervical sample, without discomfort for the user.

Those skilled in the art will enhance the knowledge presented herein and may reproduce the invention in the embodiments disclosed and in other embodiments within the scope of the appended claims.

Claims

DEVICES, KIT AND SCREENING, DIAGNOSTIC, PATHOLOGY, PROGNOSTIC AND TERANOSTIC EVOLUTION MONITORING

1 . Device characterized in that it comprises:

a plunger with a spongy material in the distal portion;

a lid located on the distal portion;

a wrapper;

wherein upon actuating the plunger by means of a plunger actuating mechanism, said sponge projects outwardly from said device and;

wherein said lid prevents fluid communication between the external environment and said spongy material in the distal portion.

Device according to claim 1, characterized in that said piston drive mechanism has a drive position and a retraction position of said piston.

Device according to claim 1 or 2, characterized in that said mechanism additionally allows rotational movement of the spongy material from the shell to its final drive position and / or from its final drive position until its retraction into the shell. .

Device according to any one of claims 1 to

3, characterized in that said spongy material is a spongy filamentous material.

Device according to any one of claims 1 to

4, characterized in that said lid is at least one of: lid opens and closes, silicone lid, organic material lid, agar lid, gelatin lid, agar and gelatin lid, lid with non-therapeutic active and organic material, lid with organic and therapeutic active material.

Device according to any one of claims 1 to 5, characterized in that it is for collecting cellular material from a user.

Medical kit comprising collection device as defined in claim 1 and sample receiving device as defined in claim 2.

A sample receiving device comprising a chamber containing a solution, a coupled diagnostic mechanism and a mechanism for eliminating part of the solution in the diagnostic mechanism.

9. Screening process characterized by comprising the following steps:

inserting the collecting device as defined in any one of claims 1 to 8 into a user's body cavity;

b) actuating the plunger so that the spongy material exits the housing;

c) retracting the plunger to collect the spongy material;

d) remove the collecting device from the body cavity;

e) inserting the distal portion of the collecting device into the sample receiving device as defined in claim 8;

f) depressing the plunger of the collecting device;

g) retract the plunger of the collecting device; and

h) on the sample receiving device, activate the mechanism for eliminating part of the solution on the diagnostic tape.

Method according to Claim 9, characterized in that the body cavity is the vaginal cavity.

1 1. Diagnostic process characterized in that it performs the process as defined in claim 9 or 10.

Pathology follow-up process characterized by performing the process as defined in claims 9, 10 or 11 sporadically.

Prognostic process characterized by performing the process as defined in claims 9, 10 or 11 sporadically.

Teranostatic process characterized by performing therapy for a pathology, physiological condition or repair of damage and further performing the process as defined in claims 9, 10 or 11 sporadically.