JP2023545621A - Absorbent tip brush biopsy devices, kits and methods - Google Patents

Abstract

A flexible coaxial tissue sampling device includes a first end extending from a proximal end of the cannula in a first state, and a first end extending from a distal end of the cannula in a second state; a displaceable wire within the intubation having a second end retracted into the end, the second end of the displaceable wire being outside the cannulation in the first state and the cell sampling structure; , and an inner porous absorbent material in the second state. Tension on the first end of the displaceable wire at the proximal end of the cannulation causes the displaceable wire, along with the cell sampling structure and the porous absorbent material, to retract from the first state to the second state. The porous absorbent material retains the fluid sample after retraction and protects the sample from contact with other tissues. [Selection diagram] Figure 2

Description

The present invention provides systems and methods for performing uterine biopsies. More specifically, the present invention is an apparatus for disrupting the endometrium and sampling cells from the endometrium while simultaneously collecting the sample with a curettage brush, aspirator, and absorbent structure.

The present technology represents an improvement over US Pat. No. 9,351,712, US Pat. These patents include Cook Medical Tao Brush™ I. U. M. C. Endometrial Sampler, and Pipelle endometrial biopsy device (Sierecki AR, Gudipudi DK, Montemarano N, Del Priore G., “Comparison of endometrial aspiration on biopsy techniques: specimen adequacy” J Reprod Med. 53(10):760-4, 2008 Oct). As shown in Figures 3 and 4, the Tao Brush™ has a head at the tip to reduce trauma when the brush reaches the base of the uterus. Figure 4 shows the brush extended from the cannulation and Figure 2 shows the brush retracted. There is an inner sleeve on the guidewire, adjacent to the brush, to center the wire, but this does not provide an interference fit and does not draw vacuum when the guidewire is retracted. Samples taken with the Tao Brush™ represent cells that have been swept or scraped from the endometrium by the bristles.

Sampling devices for cervical tissue are disclosed in US Patent Application Publications Nos. 20160331357 and 20020161313. Cervical sampling is advantageous in that the cervix and cervical ostium are more accessible and the biopsy device must be protected during passage through the cervix in order to obtain an adequate sample of endometrial tissue. , different from endometrial sampling. Furthermore, the diameter of the endometrial biopsy device is constrained by the cervical os.

20A-20C and FIG. 7 illustrate the use of Tao Brush™. The manufacturer (Cook Medical) provides the following instructions for use.
A screw cap test tube containing 1.8 ml of CytoRich® Brush Cytology Preservative (AutoCyte, Inc., Elron College, NC, USA) is placed in a test tube rack at the treatment site.
2. Place the patient in the lithotomy position.
3. Fully retract the brush sampler into the external cannula.
4. Insert the device gradually to the level of the fundus. (Figure 20A)
5. Pull the lateral cannulation all the way back to the handle. Rotate the brush sampler thoroughly. (Figure 20B)
6. To capture the endometrial sample in situ, push the outer cannula to the tip over the brush and remove the device. (Figure 20C). The normal endometrial cavity is in a contracted state, so the brush will be in direct contact with the entire endometrial surface.
7. Immediately immerse the device in 8 ml of CytoRich® Brush Cytology Preservative. (Figure 7)
8. Retract the intubation to expose the brush to the preservation solution.
9. Hold the cannula firmly and move the brush in and out of the cannula to flush out any adherent cells and tissue. The collection is generally stable in storage solution for up to several weeks.
10. Remove the brush assembly from the test tube, replace the screw cap, and submit the test tube to the laboratory for processing.

Two alternative methods for obtaining biopsy samples are recommended.
1) Rotate the brush sampler clockwise until the fiducial mark on the handle indicates a complete 360° rotation, then counterclockwise (counterclockwise) until the fiducial mark on the handle indicates a complete 360° rotation. direction).
2) Rotate the brush sampler by making 4 or 5 full 360° rotations in one direction only. Note: Fiducial marks on the handle indicate completion of 360° rotation.

To obtain uncontaminated endometrial cultures,
1. After insertion of a sterile, unlubricated speculum, disinfect the cervicovaginal region and cervix with povidone-iodine solution using a cotton swab. Note: Insert the cotton swab approximately 1.5 cm into the cervix to ensure adequate disinfection of the cervicovaginal region by povidone.
2. Insert the brush into the endometrial cavity according to steps 3 to 6 in the previous section of these instructions. A fiducial mark on the handle indicates completion of the 360° rotation.
3. Take out the sampler.
4. Wipe the round tip of the brush with 95% alcohol gauze.
5. Pull back the intubation. Prepare for morphological assessment (if necessary) by drawing a smear directly onto a sterile glass slide and immediately spray solidify.
6. For culture testing, place the brush in sterile Stuarts Transportation Medium and agitate for 5 seconds.

Figures 8A (before sample collection) and 8B (after sample collection) show the Pipelle biopsy instrument, which aspirates the sample into the cannula but does not have an exposed brush.

9 and 10A-10C illustrate designs according to U.S. Patents 9,351,712, 8,920,336, 8,517,956, and 8,348,856, which improves on the Tao Brush™ design by implementing an aspiration biopsy in addition to a curettage tissue sampling biopsy. This is achieved by providing an interference fit plunger 4 in close proximity to the biopsy brush 3, which draws a fluid sample from the uterus when the brush is drawn into the cannulation 1 by withdrawal of the wire 2. FIG. 10A shows the brush in its initial state during insertion into the uterus. FIG. 10B shows the brush extended from the cannulation. FIG. 10C shows the brush being retracted into the cannulation after the biopsy sample has been taken. However, according to the Tao Brush™ design and the designs of U.S. Pat. , an arbitrary or estimated distance, or until resistance is encountered by the tip of the brush pushing against the fundus of the uterus, which risks unnecessary tissue damage and possibly complications. U.S. Pat. a Tao Brush™ I.D. from Cook Medical (Bloomington, Ind., USA). U. M. C. Intrauterine biopsy similar to the Endometrial Sampler and modified to be a piston-like structure that is placed within the cannula and draws a vacuum as the wire is withdrawn through the cannula, drawing fluid around the guidewire into the cannula. Discusses sampling devices. Vacuum biopsy sampling devices, such as the known Pipelle endometrial suction curette, create a vacuum and draw it into the cannulation by a similar principle, but with a brush or other biopsy sample collection device at the distal end. There is no equipment.

The device is a coaxial "straw" 1 1 mm to 3 mm in diameter and 30 cm to 40 cm long that can be easily passed into the endometrial cavity with little or no discomfort. The device is flexible, yet stiff enough to apply enough force to pass through the neck. In the middle of the outer cannulation, which is an impermeable tube, a thinner inner insert 2 can be extended beyond the end of the tube 3 into the uterus. Proximal to the biopsy brush is a suction element 4 which draws fluid into the cannulation when the guidewire is withdrawn. An internal obturator disrupts the uterus to release and collect a uterine biopsy sample. The tissue sampling device includes a spirally shaped torsionally flexible wire with opposing proximal and distal ends. It also includes a plastic tube that covers a significant portion of the wire to provide additional stiffness without making the entire brush stiff.

Along the distal end of the wire is a brush containing bristles that was used to collect the tissue sample. The bristles are secured near the distal end within the spiral twisted wire, becoming thicker and tapering toward the distal end of the wire. The tapered bristles from the distal end of the device allow for more global tissue collection of the endometrium due to the shape of the endometrial cavity. There is an atraumatic bulb on the most distal end of the torsion wire. The plastic tube and torsion wire are housed within the cannula, which has a shorter length than the torsion wire, thereby allowing insertion by moving the cannula along the plastic tube to the atraumatic bulb at the distal end of the torsion wire. The brush can be covered at the time of collection and during removal after tissue collection.

To protect the brush during insertion, the cannula can be moved into position over the distal end of the twist wire prior to insertion. Having the brush covered during insertion also increases comfort for the patient and protects the brush from collecting tissue from unintended areas. After the device has been inserted to the appropriate collection depth, the cannula is returned toward the tight end of the twisted wire to expose the brush and allow tissue sample collection. The cannulation may be moved to completely expose the brush, or may be moved in stages to expose portions of the brush. This allows the physician to adjust the effective collection area of the brush based on the patient's anatomy.

The plastic tube covering the wire is graduated in centimeters along the plastic tube with marks indicating the exact length of the brush inserted into the uterus, from the distal end of the brush to the proximal end of the plastic tube. ing. This allows the clinician to know how deeply the brush is inserted into the uterus. The cannula is approximately the same length as the plastic tube and is in place over the bristles prior to insertion. The cannula may be formed of a transparent material so that the graduations on the plastic tube are visible through the cannula. The ability to measure insertion depth increases certainty that the collected tissue sample is from the correct area. After a tissue sample has been collected from the appropriate area, with the tissue sampling device still inserted, the cannula can be twisted back along the distal end of the wire over the bristles before removing the brush. can. This may ensure that the tissue sample on the brush is protected within the cannulation during removal.

Additionally, graduations along the flexible tube allow the clinician to measure the length of exposed bristles. When the physician pulls the intubation from its insertion point toward the handle, the longer the intubation is pulled, the more bristles are exposed. A scale (ruler) allows visual confirmation of this measurement and allows the clinician to accurately expose only certain lengths of bristles. This measurement allows the physician to have better control over the location at which tissue sampling takes place, and the patient's uterine size, such as the size of the uterus measured during a prior examination or estimated based on the patient's history. Allows the clinician to adjust the length of the brush based on specific parameters. Control of brush exposure increases sampling accuracy and patient comfort.

At the same time as the inner obturator is pulled back into the thin cylindrical tube, the device creates a weak suction to collect the fractured sample into the outer tube. The entire device is then withdrawn from the uterus and the sample is collected by reversing the process outside the body.

Combining two or more biopsy methods into one device eliminates pain, discomfort, and inconvenience, such as re-treatment to obtain a sufficient and accurate specimen. The combined use of multiple sample collection methods, e.g. disruption by physical means and aspiration, allows for a more gentle application of the individual methods, while violent disruption, e.g. D&C and strong suction, can be combined with e.g. can be replaced by gentle destruction and gentle suction. The combination of gentler methods in one device is safer and more effective than any single method.

The present invention provides multiple sampling modalities for intrauterine tissue biopsy. First, there are brush or tissue surface destructive modalities. Second, there are bulk fluid and suspended cellular material sampling modalities. Third, there are fluid absorption modalities. These features may be provided in combinations or subcombinations.

A preferred embodiment of the present invention provides a thin cylindrical tube with a guide wire and a biopsy sampling device at the end, using the Tao Brush™ I. U. M. C. Similar to the Endometrial Sampler, the distal tip of the biopsy sampling device is modified to have an absorbent structure that draws in cellular material. Additionally, proximal to the biopsy sampling device on the guidewire is a flange or piston structure that draws a vacuum within the tube when the guidewire is withdrawn at the end of sampling.

Surrounding the cylindrical tube may be provided a cervical stop that limits insertion of the cylindrical tube beyond a fixed distance beyond the external os of the uterus. The cervical stop may be adjustable along the cylindrical canal to control depth. Optionally, the movement of the cervical stop on the cylindrical tube may be limited in scope and placed in the neck upon initial insertion, and then provide tactile feedback once the cylindrical tube is fully inserted. Thus, the user can control both the extension of the biopsy sampling device from the end of the cylindrical tube and the depth of insertion of the cylindrical tube into the uterus. This additional parameter is meaningful because the sample taken by the brush, in particular by the flange or piston, depends on where the opening of the cylindrical tube is when it is drawn into the cylindrical tube. See U.S. Patent Nos. 9,351,712, 8,920,336, 8,517,956, and 8,348,856.

For example, a cervical stop may have a friction fit with a cylindrical tube to provide damped but smooth axial movement. The ends of the range may be provided with proximal and distal projections or O-rings to limit sliding movement. Alternatively, the smoothness or coefficient of friction of the cervical stop against the cylindrical tube may change rapidly, especially in the distal case. Indeed, sequential zones of friction variation (eg, centimeter by centimeter) may be provided to provide tactile/sensory feedback to the user to enable counting of insertion depth. Once the cervical stop reaches the proximal stop, it limits further insertion and helps avoid puncturing the uterus with the end of the biopsy sampling device.

For sample collection, a biopsy sampling device (e.g., a brush) is drawn into the cylindrical tube by retracting the guidewire while maintaining the insertion depth of the cylindrical tube, and then applying vacuum from the retraction of the flange or piston structure. The pull samples the fluid around the biopsy sampling device at that location. Therefore, the cylindrical tube should be inserted to the desired depth at which it is desired that the fluid surrounding the biopsy sampling device be sampled. Unless a restraining force is applied to the neck stop, when the cylindrical tube is withdrawn from the neck, the neck stop will no longer contact the neck.

The biopsy sampling device may extend several centimeters beyond the end of the cylindrical tube during the procedure before being pulled back into the cylindrical tube and withdrawn from the cervical os.

The distal projection or O-ring is inserted into the cervical ostium and therefore must not cause tissue trauma. The proximal projection or O-ring is not inserted into the cervical os and remains proximal to the larger cervical stop.

The distal projection or O-ring may be fixed or displaceable, and in some cases the user may wish to adjust the initial insertion depth.

As mentioned above, the distal tip of the biopsy sampling device includes a porous absorbent structure that is capable of withdrawing a cellular fluid sample from the endometrium. The tip also includes an atraumatic feature to cap the end of the guidewire (if it extends that far) and prevent puncturing of the endometrium by the biopsy sampling device. The porous absorbent structure is preferably rough or textured to provide a scraping quality that shears cells from the surface during operation of the biological sampling device. For example, a polymeric foam bulb may be formed on a cap on the end of a guidewire distal to a set of bristles extending from the guidewire, where the guidewire has a flange or piston structure. Located distally. In this case, the foam bulb is adhered to the cap and is sized and configured to be drawn into the cylindrical tube so that the porous absorbent structure is isolated from the neck during insertion and withdrawal. Similarly, this protects the porous absorbent structure from compaction and consequent loss of the sample during withdrawal.

The sample(s) obtained by the device are preferably suitable for genetic material analysis, ie PCR or RT-PCT of DNA and RNA, respectively. To avoid contamination, the materials, especially foams or other absorbent materials, are preferably synthetic and sterile.

The device is intended to collect tissue samples from the lining of the uterus (endometrium). The device has a brush at the distal end of the catheter. The brush is intended to gradually sample the endometrium by brushing the surface mucus and cells. The proximal end of the device has a handle to facilitate handling by the physician. The device has a relatively stiff outer cannula that can be moved along the length of the device (relative to the handle) to cover or expose the brush at the distal end.

The device preferably has a skirt stop, ie, a cervical stop, around the distal end of the external cannulation. The skirt stop is preferably an annular flange extending radially from the hub around the cylindrical cannula. The skirt stopper may be made of flexible silicone or polyurethane rubber.

The skirt is intended to position the device against the neck. The cervical stop may be fixed in place, i.e. by a sufficient amount to allow the end of the cylindrical tube to be inserted through the cervical epithelial cells, or manually along the lateral cannulation. may be displaced from the tip by an amount sufficient to be slidable at the tip. In general, if the cervical stop is slidable, it has a sufficient coefficient of friction against the outer surface of the cylindrical canal, and if the cervical stop abuts against the neck, the guidewire and intubation operations may be caused by the inadvertent movement of the cervical stop. It should remain axially fixed in place after placement, unless intentionally repositioned, so as not to change its position.

A series of axial marks are preferably provided to allow quantitative alignment of the cervical stop along the cannulation. As mentioned above, markings may also be provided to indicate to the user the degree of rotation of the guidewire relative to the cylindrical tube.

In some cases, parts of the biopsy process may be automated. For example, one or more electric motors may control rotation and extension of the guidewire. For example, a coreless DC motor (e.g., type 0408, 0412, or 612) motor may drive guidewire rotation, e.g., through a reduction gear transmission, whereas a similar motor may drive extension and retraction from cannulation. It may also operate as a servo for control. For example, worm gears and followers (screws and nuts) may be used. Control may be an ARM M0 or M4 based microcontroller, running an Arduino or other operating system, or directly microcoded. Advantageously, a processor is included within the RFID device, such as the NXP PN7462, NTAG203, NTA53321G0F, etc., to provide both identification and information processing functions as well as control functions.

The control is preferably reusable, while the biopsy catheter is preferably single use and transported to a pathology laboratory for analysis. The control is preferably autoclavable or gas sterilizable, but may also be waterproof and may be sterilized and/or cleaned by immersion in a sterilization/disinfection solution. The microcontroller and power supply may be wirelessly coupled to the motor/actuator unit, for example coupled via Qi or other wireless standard inductive coupling. As discussed below, other automated functions are possible using electronic assistance, and the basic sample collection functions of a single biopsy device can be reasonably performed by a skilled user without electronics. be done.

The skirt stopper is preferably made of rubber, silicone, or a material with rounded edges, providing the desired properties, and having sufficient resiliency to avoid unintentional trauma if excessive pressure is applied by the user. It is made of elastomer such as plastic.

The device is intended to be advanced into the patient with the brush covered by the external cannulation until the skirt reaches the neck and can be advanced no further. After the skirt stops against the cervix, the brush is advanced beyond the end of the cannula by moving the guidewire relative to the cannula to expose the brush inside the uterus and allow tissue sampling. The skirt provides force for intubation when pressed against the neck.

The device also has an O-ring, flange or piston secured to the main shaft of the catheter, ie the guidewire. In the outer cannulation, the cylindrical tube and O-ring, flange or piston create a seal with each other, and suction (vacuum) is applied to the distal end of the catheter to secure the tissue sample as the guidewire and brush are drawn into the cannulation. ).

The device is removed from the patient with the brush covered by the outer cannula. A stop may be provided to limit withdrawal of the guidewire into the cannulation. For example, an annular or cylindrical member mounted at a fixed location within the cannulation may interfere with the O-ring (or flange or piston), thereby limiting retraction.

The device is preferably sterile and intended for single use only. Advantageously, the guidewire and cannula may be easily cut with scissors (shears) or wire cutters to reduce the material that needs to be transported for analysis. A cut point may be provided and is more easily severed than the remaining cut points. Typically, twisted or braided stainless steel guidewires are difficult to cut or damage fine scissors. However, a weak section of the wire may be provided either by modifying the wire in the weak area or by providing an insert.

Barcodes or 2D barcodes may be used for identification, but writable RFID devices must be readable without being visible (e.g., wrapped or coated). , has the advantage of being easily updatable during use (writable tags), avoids line-of-sight requirements, and allows cryptographic authentication and access restrictions (depending on the integrated circuit chosen). In some cases, identities and related information may be stored on blockchains or distributed blockchains, avoiding the need for centralized access on the one hand, and single points of failure and implicit trust on the other hand. Thus, using a cryptographic handshake, an RFID device associated with a biopsy device, e.g. Ad-hoc or structured information, such as identification information, which may be a personal information, and treatment and reporting details, may be stored. In some cases, the preferred standards for RFID may be according to ISO 11784 and ISO 11785, which operate at a lower frequency than ISO 14443 and therefore may also use a ferrite antenna with a coil wound around it. It often has a cylindrical shape factor and facilitates placement or molding into the handle.

In some cases, the handle is disconnected from the handle to facilitate transportation and analysis to a laboratory for analysis. In that case, if the RFID is in the handle, it will be separated from the associated sample. In that case, RFID may be provided on the intubation. RFID semiconductor devices are typically less than 2 mm, potentially less than 1 mm, and may therefore be mounted on the cannulation. However, RFID antennas are generally configured as a coil around an area. In this case, the antenna may be long and thin and may be wrapped around the intubation. For example, the antenna may be embedded in the cannula or additionally printed on its surface.

The identification may also be a linear barcode on the intubation or a QR code on a tag associated with the handle or handle end of the device. This may be printed or laser engraved.

According to another embodiment, identification is provided on the sample collection chamber (cup) in which the collected sample, ie the brush, sponge tip, and fluid drawn into the cannulation, is placed after the biopsy. In that case, the RFID may be a module embedded inside the sample collection container, outside the sample collection container, or in the wall or top of the sample collection container. The sample collection container may have a pocket therein for holding a brush. The sample collection container may be prefilled with a preservative and/or fixative solution. Typically, the tip of the biopsy device is severed prior to placement within the sample collection container. The pocket may be tightly closed around the tip to prevent reopening outside the pathology laboratory without evidence of tampering. Alternatively, the pocket may have a flap closure that can be reopened.

The sponge tip has limited fluid absorption and therefore cannot be squeezed to expel its fluid payload once drawn into the cannulation. For example, the expansion of the sponge when absorbing fluid may be between 0 and 30%. For example, absorption may occur primarily by capillary action rather than by expansion.

In some cases, the RFID can be separated from the biopsy device and manually transferred to (or in conjunction with) the sample collection container using the tip.

Alternatively, the RFID device may act similarly to a contactless RF credit card, for example according to NFC (en.wikipedia.org/wiki/Near-field_communication) or other standards such as ISO/IEC14443. Instead of storing information on the device, the device provides secure authentication for itself, based on a cryptographic handshake, linking access to records based on proof of the device's authenticity. Access to sensitive information may then require subsequent users in a pathology lab, for example, to have verified credentials. For example, a physician collecting a sample may program a patient record for a particular laboratory. Alternatively, the laboratory may provide the biopsy device to a physician who can then use the private key or PIN to read and use the electronically stored information.

The biopsy device may have a writable RFID device and the written information may be encrypted or cryptographically protected. The need for RFID arises from contact avoidance and, in the case of biopsy specimens, may be associated with biohazards and contamination. RFID, on the other hand, allows tags to be read and written without breaking the sanitary or hermetically sealed enclosure. The writable RFID device may contain various relevant parts of the treatment record and/or patient record, but only if the stored information is necessary or reasonably related to the analysis and reporting of the biopsy device. carefully stipulate that it should be shortened to . In some cases, the biopsy device is stored after receipt and may contain, for example, forensic evidence, in which case the tag may be updated or automatically updated after the initial sample collection, storage chain, storage condition. It may be advantageous to include the following.

According to another embodiment of the invention, a multiple sample biopsy device is provided that is capable of acquiring and separating multiple biopsy samples taken at one time. According to this embodiment, the biopsy instrument is placed into an anatomical opening such as the cervical os or anus. Advantageously, a projection similar to the cervical stop described above provides a positional reference for the outer part of the opening. This protrusion may be part of the design or an added element to achieve the desired insertion depth reference function.

The multi-sample biopsy device may advantageously be automatically controlled with an electronic microcontroller. In this case, the selection and actuation of multiple sample components may be controlled by a microcontroller and automatic. Similarly, in some cases, biopsy sampling may benefit from automated control. For example, collection of different isolated liquid samples during a procedure may involve a controlled vacuum source and sample isolation. Samples are electronically labeled and their identity managed based on electronic or RFID tags.

The biopsy devices according to this multiple sample embodiment may each be the same or different, such as an endocervical sampler, an endometrial sampler, a punch sampler, and an endometrial sampler with suction. The present invention also provides a multi-biopsy sampling device. Each instrument is operable by a guidewire to extend the instrument sampling head beyond the end of the cannulation, twist relative to the cannula, and retract the instrument sampling head within the cannula; 1. It is provided as a device inside an intubation, such as a 5 mm to 4 mm tube.

In addition to providing control of the advancement of the biopsy instrument relative to the cannula, each cannula is selectively inserted into the opening and advanced into the organ with the biopsy instrument retracted into the cannula. The biopsy device can then be controlled to be withdrawn from the organ while being retracted into the cannula.

In some cases, the cannulation itself may be bendable or angularly navigable to direct the biopsy instrument to the desired area. A bendable cannula may be uniaxial, i.e., typically with curvature of the end of the cannula as a result of tension on a tension element, such as a cable, guide wire or filament, attached to the wall of the cannula. There may be. Shape memory alloys (SMAs) such as titanium nickel alloys may be used as thermally controlled actuators. The temperature may be ohmic heating controlled with a control current. Controlling the angle of curvature and the angle of rotation of the cannulation relative to the organ provides a reasonable range of control. The SMA elements may be selectively provided at locations along the length of the cannula and may be actuated by a signal along a serial control line that is connected to an addressable serial embedded in the cannula. received by a receiver integrated circuit. Multiple receivers may be provided, providing the possibility of complex movements.

Similarly, punches, or snares, or encapsulated biopsy devices can also be controlled by tension, which may be wires or polymer filaments or SMA actuators. A single guidewire with a single degree of freedom (advancement/retraction) is the simplest case, but additional controls and degrees of freedom may be provided.

In some cases, "blind" sampling can be performed, for example in a short tube or distal to the organ to the orifice.

In other cases, for example within the lumen of a larger organ, some imaging guidance may be desirable. Accordingly, the device may be used with an endoscope and/or may include an endoscopic camera, such as a 1 mm to 3 mm endoscopic camera. Typically, such devices rely on optical fibers from the tip to the imager for both illumination and imaging. However, according to one embodiment of the present technology, the imager circuitry and lens are at the tip of an endoscope, and the endoscope is positioned near the end of the biopsy sample collection device to provide direct access to the biopsy procedure. It also realizes real-time imaging.

For example, On Semiconductor offers a variety of compatible devices, including the MT9V115 1/13” VGA, OV6922 1/18” 1/4 VGA imager, and OVM6946 1/18” 400×400 imager. The imaging device may be included as part of a micromodule that transmits the images as a data stream via an electrical interconnect (or wirelessly).The imaging device typically faces the biopsy instrument. A set of LEDs, or an LED illumination fiber, illuminates this field of view.A camera is not required for all modes of operation, i.e. for all sample collection procedures, but if it is provided, it will illuminate the entire procedure. The camera may be near the end of the cannulation and may be advanced into the organ with each cannulation of the biopsy instrument during the procedure. Control of the electronic device, including and/or network communications, may be based on Linux or a real-time Linux controller, and may include, for example, a Raspberry Pi 4, ESP32, or other known controllers or multi-core controllers. , may be similar to these.Typically, medical devices do not use consumer grade devices or operating systems unless there is harm to the patient from abnormal operation of the device.Biopsies In the case of devices, there is a potential for harm, therefore secure hardware and software with code and peripheral device authentication is preferred.

Advantageously, the video signal from the imaging device may be conveyed using the guide wire controlling the biopsy instrument as a power and/or signal conveyance path. It should be noted that the operating voltage is typically low, eg <3.3V, so there are no dangerous conditions for the patient in case of electrical leakage. However, the power carrying members may be insulated to further reduce risk and improve signal integrity. Wireless transmission can also be provided, for example to a nearby wireless receiver, thereby eliminating the need for wired transmission. In that case, the device may have a built-in battery, receive operating power via conductors, which may advantageously include a guidewire, or receive power through inductive coupling. Preferred guidewires are multi-stranded wires so that they can transmit power and ground as well as signals if the strands are insulated from each other. Since there is no compelling reason why the guidewire should be uninsulated, this allows for expanded utilization of existing structures at little additional cost and complexity. The tip of the device may include LED lighting. Indeed, in some cases fluorescent dyes may be used to selectively highlight suspicious tissue, and in particular UV LEDs may be used to illuminate the fluorescent dyes to reveal the area to be sampled. Good too. In some cases, the dye is a UV activated therapeutic agent. In that case, the biopsy component of the catheter is optional.

A biopsy device according to multiple biopsy sample embodiments provides a barrel cartridge with various biopsy instruments in angularly displaced positions, or a linear or rectangular array of biopsy instruments. One method of selectively actuating a particular instrument is for a user-controlled manipulator to provide functional control over one of a plurality of biopsy tips, such as cannulation extension and retraction and guidewire extension. The goal is to provide the barrel with a single operating position for retraction and rotation. As mentioned above, there may also be a feature for cannulation bending due to tension on another working filament. The remaining biopsy instruments within the barrel may be restrained in their respective undeployed positions, eg, remain fixed in place. Therefore, the number of degrees of freedom of the actuator may be limited to the maximum required by instrument selection in addition to any single instrument.

Because the barrel or array is larger than the minimum cannulation diameter for a single instrument, the barrel or array is retained outside the organ orifice and used to engage and disengage the respective biopsy instruments. A mechanism is also external to the organ opening and may, for example, be rotated into position to release one instrument while locking another instrument in a retracted position. In this way, relatively large arrays (circular or spatial arrays), eg 4 mm to 20 mm, may be provided with 2 to 30 biopsy instruments. Advantageously, the end of the barrel or actuator mechanism serves as a cervical stop that limits the insertion distance of the cannulation into the organ, such as the uterus, and provides a clear position reference.

According to one embodiment, each biopsy instrument within the device is separate (ie, has a separate predetermined guidewire actuator) and there is no control switching. Thus, for a biopsy device with four deployable biopsy instruments, there are four separate cannulae with respective guidewires extendable from the cartridge. This allows the physician to select the appropriate biopsy instrument for each procedure from standard or custom designs. While the actuating instrument is in use, the unused instrument remains external to the organ. In some cases, multiple instruments may be advanced into the organ, for example, in which case an endoscope is provided as one of the available instruments, and a specific biopsy instrument or a single biopsy instrument is Not connected.

On the other hand, in a second embodiment, mechanisms are provided for each separate biopsy device to mechanically engage separately, e.g., intubation, guidewire, and bending wires, and a single control system has multiple A biopsy control path extending from the cartridge includes a biopsy control path and an additional biopsy instrument selection path. For example, multi-directional clamps, bayonet sockets, quick releases, SMA actuators, or magnetic mechanisms may be provided to individually engage each biopsy instrument in the actuated position. The cartridge is typically round and centered at the opening during the procedure so that the non-deployed biopsy device is off-centered within the cartridge when not in use. When the lockout/clamp control mechanism is moved into the actuated position, such as by rotation and alignment, the respective biopsy instrument's control mechanism is also connected and actuated.

A camera may also be attached to and advance with the operative biopsy instrument. Alternatively, the camera may be pre-inserted into the biopsy instrument and placed separately from the biopsy instrument.

Note that the one or more devices, either alone or as part of another device, have a resilient, fluid-absorbing, textured surface that scrapes the surface to expose the tissue and collect the sample. May include. According to one embodiment, the absorbent structure is rough when dry and as it is hydrated it becomes more flexible. The absorbent element may be impregnated with salts or polymers that dissolve after brief exposure to intrauterine fluids.

In some cases, electrical or electronic controls may be used, for example, to latch the mechanical control mechanism, extend the intubation to the desired insertion depth, rotate the brush, and retract the intubation and/or the biopsy brush into the cannula. A mechanism may be provided on the cartridge. Typically, the extension and axial manipulation of the biopsy brush is controlled by the user, and although not automatic, fully automated biopsy is also possible.

Preferably, each biopsy instrument has a mechanical limiter to control and limit movement within a predetermined range, where the predetermined range varies depending on the intended use of the respective application. may be different for each biopsy device. This avoids user error and resulting harm to the patient, and also helps ensure that a usable specimen is obtained. The axial control limit is referenced to the outer surface around the insertion opening and the end of the barrel, and a ring or protrusion around the barrel is used to maintain this positional reference without slipping into the opening. Therefore, it is advantageous.

For example, an endocervical brush typically extends the intubation 0 cm to 2 cm beyond the orifice, an endometrial brush typically extends the intubation 2 cm to 10 cm beyond the cervix into the uterus, and a brush biopsy The device extends 1 cm to 3 cm beyond the end of the cannulation. Endocervical and endometrial brushes may or may not be equipped with suction, with suction being achieved by mechanical action of a plunger as the guidewire controlling the brush is drawn into the cannulation, or through the cannulation. This may be achieved by a vacuum applied from the cartridge or beyond.

According to another embodiment, instead of a plunger, an O-ring or a piston in the intubation directly proximal to the brush and distal to the cervical stop, a plunger, e.g. It is also possible to generate a sampling vacuum in a more proximal region of the testing device. This may be at the cervical stop or distal to the cervical stop. Therefore, the volume drawn into the cannulation by displacement of the guidewire in this wide cross-sectional area exceeds the volume of the brush tip, allowing for larger volume samples and/or higher vacuum forces. A fluid such as water, saline or silicone oil may be provided around the guidewire within the cannulation to allow vacuum hydraulic communication instead of pneumatic communication. Water, saline, or oil may be confined to the device and isolated from the biopsy sample and patient.

Puncher or cup biopsy instruments are typically used under visual observation using a video imaging device, and the user is expected to control the device during use, so there are no mechanical constraints in this situation. less often.

Thus, the present design allows multiple biological tissues to be harvested at one time from different regions of the organ while remaining separated from each other. From the patient's point of view, this is advantageous because the sampling procedure is made easier and the combination of time and financial burden is generally less than when using separate biopsy instruments. It is also efficient to use in combination with a single imaging device used for multiple biopsy procedures. Finally, in the case of a cartridge that detaches from a standard handle, the cartridge provides an efficient way to organize and label (identify) specimens from one patient, as well as various specimens from the same patient and organ. Streamline pathological examinations. Finally, each sample is accurately depth labeled relative to the aperture, providing clinically relevant information compared to traditional biopsy instruments that do not provide a precise depth reference. Additionally, a memory card, such as a microSD card, may accompany the cartridge, and the memory card contains video and/or operating history information for each biopsy instrument that is automatically recorded and maintained, making it convenient for pathologists to patient's record or as part of the patient's record. As mentioned above, contactless electronic identification and/or information storage and/or safety authentication devices, such as ISO 14443 RFID devices, may be used to avoid contamination issues when using contact devices. Alternatively, barcodes may be used that allow reading of records in a database or distributed database/blockchain.

A flexible coaxial tissue sampling device comprising: a cannula having a wall and a hollow space within the wall; and a displaceable wire within the hollow space, the displaceable wire extending from a proximal end of the cannula; a displaceable wire having one end and a second end configured to extend from the distal end of the cannula in a first state and retract into the distal end of the cannula in a second state; the second end of the displaceable wire includes an aspiration element, a cell sampling structure, and a porous absorbent material, the cell sampling structure and porous absorbent material being outside the cannulation in the first state. in the second state, the suction element is proximal to the cell sampling structure and the porous absorbent material, and the flexible coaxial structure is inside the cannula at the proximal end of the cannula. Tension on the first end results in retraction of the displaceable wire from the first state to the second state, displacing the displaceable wire into the intubation and the suction element, the cell sampling structure, and the porous absorbent material. the porous absorbent material is configured to cause a corresponding proximal displacement of the cannula and to aspirate media outside the cannula to the distal end of the cannula; It is an object of the present invention to provide a tissue sampling device configured to hold a sample of a fluid sample obtained by the tissue sampling device.

A flexible coaxial tissue sampling device comprising: a cannula having a wall and a hollow space within the wall; and a displaceable wire within the hollow space, the displaceable wire extending from a proximal end of the cannula; a displaceable wire having one end and a second end configured to extend from the distal end of the cannula in a first state and retract into the distal end of the cannula in a second state; , the second end of the displaceable wire includes a cell sampling structure and a porous absorbent material, the cell sampling structure and porous absorbent material being external to the cannulation in the first state; In the second state, the flexible coaxial structure is inside the cannula such that tension on the first end of the displaceable wire at the proximal end of the cannula causes retraction of the displaceable wire from the first state to the second state. causing displacement of the displaceable wire, the cell sampling structure, and the porous absorbent material into the intubation, the porous absorbent material absorbing the fluid obtained in the first state after the transition to the second state. It is also an object to provide a tissue sampling device that is configured to hold a sample and protect the tissue from contact with the second end of the displaceable wire.

A biopsy method comprising: an intubation having a wall and a hollow space within the wall; a displaceable wire within the hollow space, the displaceable wire having a first end extending from a proximal end of the cannulation; a second end configured to extend from the distal end of the cannula in a first state and retracted into the distal end of the cannula in a second state; the second end of the displaceable wire includes a cell sampling structure and a porous absorbent material, the cell sampling structure and the porous absorbent material being connected to the first end; the flexible coaxial structure being outside the cannula in the second state and inside the cannula in the second state; inserting the displaceable wire into the uterus beyond the internal cervical os; pushing a first end of the displaceable wire into the cannulation to cause the flexible coaxial structure to assume a first state; manipulating the displaceable wire to rub the cell sampling structure against the endometrium and absorb fluid into the porous absorbent material to obtain a cell sample while protecting the endometrium from invasion by the tip of the displaceable wire; applying tension to the first end of the displaceable wire at the proximal end of the cannulation to retract the displaceable wire from the first state to the second state while retaining the absorbed fluid within the porous absorbent material; , thereby preventing retraction of the displaceable wire, cell sampling structure, and porous absorbent material into the intubation and contamination of the biopsy sample retained on the cell sampling structure by cells within the cervix and vagina. It is a further object to provide a biopsy method comprising: capping the distal end of the cannulation with a porous absorbent material.

The cell sampling structure includes a brush having a plurality of bristles extending radially from a displaceable wire and terminating in a porous absorbent material including an atraumatic bulb covered by a layer of open cell foam;
further comprising a suction element displaceable with the displaceable wire and proximal to the cell sampling structure and the porous absorbent material, the suction element distal to the cannulation when the displacement wire is withdrawn into the cannulation. The device is configured to create negative pressure within the device.

A porous absorbent material may cap the second end of the displaceable wire to protect tissue from damage by the tip of the displaceable wire. A porous absorbent material may be formed at the tip of the second end of the displaceable wire. The porous absorbent material within the intubation in the second state protects the biopsy specimen within the intubation obtained during the transition from the first state to the second state from contamination during withdrawal of the distal end from the patient. It may be protected by The porous absorbent material may be adapted to absorb biopsy samples for nucleic acid analysis. The porous absorbent material may be a sponge.

The cell sampling structure may include a brush. The brush may include a plurality of bristles extending radially from the displaceable wire.

The coaxial structure may be configured to be inserted through the endocervical ostium of a human uterus to remove an endometrial biopsy sample, and sliding the depth stop on the intubation causes the coaxial structure to be in the first state. has an adjustable depth during the biopsy procedure while maintaining the

The coaxial structure may be configured to be inserted to a predetermined depth into the internal cervical os of a human uterus and withdrawn from the uterus to remove an endometrial biopsy sample. The coaxial structure is inserted into the cervical os to a predetermined depth with the displaceable structure in a second state, and extended to a first state with the cell sampling structure in the uterus, and the coaxial structure is extended into the first state with the cell sampling structure in the uterus. operated by a user by movement of the first end of the displaceable structure to remove cells from the cannulation, and to create a vacuum to draw a liquid sample around the cell sampling structure into the distal end of the cannulation. The displaceable structure may be further configured to be retracted to the second state within the uterus and retracted from the cervical os with the displaceable structure in the second state.

The cell sampling structure may include a spiral twisted steel wire with extending bristles welded to a proximal guidewire.

The porous absorbent material formed at the second end may include urethane foam disposed over a cap terminating a spiral twisted steel wire.

The cannula may have an outer diameter of 0.15 inches and a length of 20 cm to 50 cm.

The tissue sampling device includes a slidable skirt disposed on the outer surface of the flexible cannula that is configured to prevent insertion of the flexible cannula into the patient's uterus beyond the axial position of the skirt stopper. It may further include a stopper.

One embodiment includes at least two flexible coaxial structures, each having a respective cannulation, a respective displaceable wire, a respective suction element, a respective cell sampling structure, and a respective porous absorbent material. at least two flexible coaxial structures having at least two flexible coaxial structures, when engaged, tension and compression are transmitted from the user interface to the displaceable structures to move the displaceable structures between a first state and a second state. selectively engages each displaceable wire of each flexible structure to the user interface such that tension and compression are not transferred from the user interface to the displaceable structure when disengaged. a housing configured to engage and disengage.

The tissue sampling device may further include, for example, an electric motor configured to move the displaceable structure axially and rotationally.

Accordingly, a tissue sampling device comprising: a flexible cannula having at least a distal end configured to maintain an internal vacuum; and a displaceable structure within the cannula; forming a displaceable structure having a first end extending from the proximal end of the cannula and extending from the distal end of the cannula in a first state and retracted into the distal end of the cannula in a second state. a second end configured to have a cell sampling structure formed at the distal tip, the second end of the displaceable structure having a cell sampling structure preceded by a proximal suction element; the coaxial structure has a distal porous absorbent material such that tension on the first end of the displaceable structure at the proximal end of the cannulation changes the displaceable structure from a first state to a second state. It is an object of the present invention to provide a tissue sampling device configured to create a suction that causes retraction and displaces media outside the cannulation into the cannulation distal of the piston.

The tissue sampling device may further include a displaceable element with the displaceable structure, the element applying negative pressure within the tubular cannula distal to the element when the displaceable wire is drawn into the tubular cannula. is configured to cause

The cell sampling structure may include a brush.

The brush may include a plurality of bristles extending radially from the displaceable structure. The brush may have a helical cross-sectional profile.

The coaxial structure may be configured to be inserted into the cervical os of a human uterus to a predetermined depth and withdrawn from the cervical os of the uterus to retrieve an endometrial biopsy sample.

The coaxial structure is inserted into the cervical os to a predetermined depth with the displaceable structure in a second state, and extended to a first state with the cell sampling structure in the uterus, and the coaxial structure is extended into the first state with the cell sampling structure in the uterus. operated by a user by movement of the first end of the displaceable structure to remove cells from the cannulation, and to create a vacuum to draw a liquid sample around the cell sampling structure into the distal end of the cannulation. The displaceable structure may be further configured to be retracted to the second state within the uterus and retracted from the cervical os with the displaceable structure in the second state.

The cell sampling structure may include a spiral twisted steel wire with extending bristles welded to a proximal guidewire. The porous absorbent material formed at the distal tip may include urethane foam disposed over a cap terminating a spiral twisted steel wire.

The cannula may have an outer diameter of 0.15 inches and a length of 20 cm to 50 cm.

The tissue sampling device further includes a skirt stopper disposed on the outer surface of the flexible cannula configured to prevent insertion of the flexible cannula into the patient's uterus beyond the axial position of the skirt stopper. You may prepare. The skirt stopper may include a flange-like element on the outer surface of the flexible cannula, the flexible cannula being inserted to a predetermined depth into the cervical os of the human uterus to remove an endometrial biopsy sample from inside the uterus. the displaceable wire is inserted into the cervical os to a predetermined depth with the displaceable wire in the second state, and is configured to be withdrawn from the cervical os of the uterus after an endometrial biopsy sample has been obtained; While the sampling device is in the uterus, it is extended to a first state and manipulated to remove endometrial cells by movement of the first end of the displaceable wire, and the liquid sample surrounding the cell sampling device is expanded into a tubular shape. The displaceable wire is configured to be retracted to a second state within the uterus and retracted from the cervical os with the displaceable wire in the second state to draw a vacuum into the distal end of the cannulation.

The tissue sampling device includes a plurality of flexible cannulae, each having at least a distal end configured to maintain an internal vacuum, and a plurality of flexible cannulae within each flexible cannulae forming a set of coaxial structures. Each of the displaceable structures, when engaged, transmits tension and compression from the user interface to the displaceable structure to transition the displaceable structure between a first state and a second state, and when engaged. and a housing configured to selectively attach the respective displaceable structure to the user interface such that tension and compression are not transferred from the user interface to the displaceable structure when released. good.

The tissue sampling device may further include an electric motor configured to displace the displaceable structure. The tissue sampling device may further include an electric motor configured to rotate the cell sampling structure.

a plurality of flexible cannulae and a displaceable structure within each cannulae forming a coaxial structure, each displaceable structure having a first end extending from a proximal end of the cannulae; a second end configured to extend from the distal end of the cannula in the state and retracted into the distal end of the cannula in the second state; a displaceable structure having a cell sampling structure distally terminated with a porous absorbent foam; and a displaceable structure having tension and compression transmitted from a user interface to the displaceable structure when engaged. transitioning the body between a first state and a second state, and connecting each displaceable structure to a user interface such that tension and compression are not transferred from the user interface to the displaceable structure when disengaged; It is also an object to provide a plurality of sample biopsy device comprising: a housing configured to selectively attach to a housing;

A method of tissue sampling comprising a coaxial cannulation comprising at least a distal end configured to maintain an internal vacuum and a displaceable structure within the cannula forming a coaxial structure. a structure, a displaceable structure having a first end extending from a proximal end of the cannula; and a displaceable structure extending from a distal end of the cannula in a first state and within the distal end of the cannula in a second state; a second end configured to be retracted; the second end of the displaceable structure is preceded by a piston and terminated by a porous absorbent tissue scraping structure; a first end of the displaceable structure at the proximal end of the cannulation for retracting the displaceable structure from the first state to the second state to generate a vacuum; It is also an object to provide a tissue sampling method comprising: applying tension to a tissue sample.

The coaxial structure may further include a skirt around the flexible cannula configured to limit the depth of insertion of the flexible cannula into the human neck.

The coaxial structure is inserted into the cervical os of a human uterus to a predetermined depth defined by the axial position of the skirt around the flexible cannulation to retrieve an endometrial biopsy specimen, and It may be configured to be drawn from.

The method includes inserting the distal end of the coaxial structure into the cervical ostium of the uterus to a predetermined depth while the displaceable structure is in a second state, and the cell sampling structure is in the uterus. manipulating the first end of the displaceable structure to remove cells within the uterus; and manipulating the first end of the displaceable structure to remove cells within the uterus; retracting the coaxial structure within the uterus to a second state to create a vacuum to draw a liquid sample into the distal end of the cannula; and with the displaceable structure in the second state; retracting the distal end of the structure from the cervical os.

The cell sampling structure may include a brush having a plurality of bristles extending radially from the displaceable structure and terminating in an atraumatic bulb covered by an open cell foam layer.

The cell sampling structure may include a spiral torsionally flexible wire with extending bristles and may further include twisting the guidewire to rotate the cell sampling structure.

A flexible coaxial biopsy device comprising: a tubular cannula having walls configured to maintain an internal vacuum relative to an exterior of the tubular cannula having a displaceable wire within the tubular cannula; a cell sampling device, the cell sampling device and the porous absorbent structure each being configured to disrupt a tissue surface and attached to a displaceable structure distal to the element; , configured to protrude from the distal end of the tubular cannula when the displaceable element is disposed in the first state and to be received within the distal end of the tubular cannula when the displaceable element is disposed in the second state. Another object of the present invention is to provide a flexible coaxial biopsy device comprising: a cell sampling device;

The flexible coaxial biopsy device may further include a flange-like element on the outer surface of the tubular cannula configured to limit the depth of insertion of the tubular cannula into the neck.

The cell sampling device may include a plurality of bristles extending outwardly from a displaceable wire and terminating at their distal ends in an atraumatic bulb covered by a porous absorbent structure including a layer of foam.

The flexible coaxial biopsy device is inserted into the cervical os of the human uterus to a predetermined depth to retrieve the endometrial biopsy sample from inside the uterus, and after the endometrial biopsy sample is obtained, it is inserted into the cervical canal of the uterus. It may be configured to be withdrawn from the mouth.

The flexible coaxial biopsy device may further include an element that creates a negative pressure within the tubular cannula when the displaceable wire is drawn into the tubular cannula.

The biopsy brush described above can also be modified for use as an anal biopsy brush, and the endometrial biopsy brush and anal biopsy brush can optionally be combined as a kit (for single brush use). ) may be provided alone with a vial of preservation solution or with multiple vials of preservation solution for a kit. The kit is preferably in a sterile package, the package may be double wrapped, and includes a biopsy brush, a vial of preservation solution, and optionally an acceptable lubricant for cytological sampling. Optionally contains a disposable sterile sheet or drape.

Anal biopsy brushes differ from intrauterine biopsy brushes in that they are shorter due to the shorter working distance between the physician or caregiver and the patient's orifice. For intrauterine applications, the intubation is typically 20 cm to 25 cm long, with a 4 cm long brush, exposing 2 cm of the guide wire, making the wire 26 cm to 31 cm long, and connecting the wires. A skirt is provided over the end of the handle and approximately 4 cm from the distal end on the cannula.

Anal biopsy brush cannulae are typically 8 cm to 12 cm in length with a skirt located approximately 4 cm from the distal end. For example, an anal biopsy brush has a long guide wire with a skirt located 4 cm from the distal end and a length of 14 cm to 18 cm for sampling up to 6 cm beyond the end of the cannulation within the rectum. It may have an intubation length of 8 cm. An absorption tip is preferably provided.

The kit therefore includes a long intrauterine biopsy device with an intubation length of about 20 cm, a short anal biopsy device with an intubation length of about 8 cm, two vials of cell preservation solution and an aqueous cytologically acceptable biopsy device. may include a packet of possible lubricant (e.g., Surgilube®, which is preferably carbomer-free), a sterile drape, and accompanying labeling instructions (optionally printed on the package). . With the brush in the retracted position, any lubricant should be applied to the outer surface of the cannula between the skirt or flange and the tip, being careful not to get any lubricant on the end of the cannula or brush. be.

1 shows a first embodiment of a biopsy device according to the invention with a cylindrical sponge cap in a retracted and extended state; FIG. 1 shows a first embodiment of a biopsy device according to the invention with a cylindrical sponge cap in a retracted and extended state; FIG. Figure 3 shows a prior art Tao Brush in the retracted and extended states, respectively, for intubation. Figure 3 shows a prior art Tao Brush in the retracted and extended states, respectively, for intubation. 2 shows a second embodiment of the biopsy device according to the invention with a round cap in the retracted and extended states; 2 shows a second embodiment of the biopsy device according to the invention with a round cap in the retracted and extended states; Figure 3 shows the transfer of a biopsy specimen to a tube containing brush cytology preservative. Figure 3 shows the prior art Pipelle endometrial biopsy device in extended and retracted states, respectively. Figure 3 shows the prior art Pipelle endometrial biopsy device in extended and retracted states, respectively. Prior art endometrial biopsy brushes with suction according to U.S. Pat. show. Prior art endometrial biopsy brushes with suction according to U.S. Pat. show. Prior art endometrial biopsy brushes with suction according to U.S. Pat. show. Prior art endometrial biopsy brushes with suction according to U.S. Pat. show. Prior art endometrial biopsy brushes with suction according to U.S. Pat. show. Figure 3 shows a guide wire and biopsy brush according to the invention with a sponge covering the atraumatic bulb. 2 shows a thin cannulation equipped with a skirt stopper according to the invention; Figure 2 shows a complete biopsy device according to the invention with a manual action handle, skirt stopper, cannulation, guide wire, brush, O-ring, and sponge covering the atraumatic bulb. Figure 3 illustrates the configuration of an independently controllable biopsy multi-sample biopsy device showing four similar biopsy sample collection instruments. Figure 3 illustrates an independently controllable biopsy multi-sample biopsy device configuration showing four different biopsy sample collection instruments. Figure 2 shows details of a selector that allows operation of a single biopsy sampling device within a barrel cartridge. 1 shows a shirt stopper according to the invention; Figure 3 shows a side perspective view of a prototype biopsy device with an absorbent sponge material at the distal tip of the biopsy device with a schematic diagram of sample absorption. A specimen collection container with a pocket for holding a biopsy brush is shown. 1 shows insertion of a prior art biopsy device into the uterus; 1 illustrates the manipulation of a prior art biopsy instrument into the uterus for tissue sampling; Figure 3 shows withdrawal of a prior art sampling brush to intubation for subsequent removal from the uterus. Figure 3 shows a side view of the vaginal canal/uterus in cross section. It is shown that the device according to the invention moves into the vaginal canal, enters the cervix and stops when the skirt brings the cervix into contact with a brush enclosed within the cannulation inside the uterus. The brush is shown extending the entire length inside the uterine cavity with an atraumatic bulb and an absorbent sponge covering the distal tip.

Example 1: A preferred embodiment of the invention consists of an intrauterine biopsy device having an outer thin-walled tube with an outer diameter of about 2.25 mm and an inner diameter of 1.2 mm, and a length between 20 cm and 50 cm, such as 22 cm. . The tube may be a transparent, bendable but self-supporting plastic tube, for example made of nylon. The guidewire is preferably a twisted stainless steel wire with a diameter of about 0.1 mm to 0.2 mm and sufficient mechanical properties to transmit forces for extension and retraction of the brush during use. At the distal end of the guidewire is a biopsy brush shown in FIGS. 8 and 11 with an atraumatic bulb at the tip. The brush is approximately 4 cm long and, when extended, extends approximately 2 cm beyond the end of the cannulation. The O-ring preferably remains within the cannula throughout its entire range of travel to avoid the problem of re-engaging the ends of the cannula. For example, the O-ring (or more generally the plunger attached to the wire) is located, for example, 2 mm to 5 mm from the end of the cannulation during extension.

An anal biopsy device may also be provided having an outer thin-walled tube with an outer diameter of about 2.25 mm, an inner diameter of 1.2 mm, and a length between 8 cm and 12 cm, such as 8 cm. The tube can be a transparent, bendable but self-supporting plastic tube, for example made of nylon. The guidewire is preferably a twisted stainless steel wire with a diameter of about 0.1 mm to 0.2 mm and sufficient mechanical properties to transmit forces for extension and retraction of the brush during use. At the distal end of the guidewire is a biopsy brush shown in FIGS. 8 and 11 with an atraumatic bulb at the tip. Brush for anal biopsy devices may be 4 cm long and include an O-ring or plunger located 2 mm to 5 mm from the end of the cannulation when the brush is extended.

The wires are marked at regular intervals, such as 1 cm increments, so that the physician or biopsy device operator can estimate brush insertion relative to the proximal end of the cannulation.

A biopsy brush is formed at one end that enters the uterus or anus. An interference fit O-ring around the guide wire, similar to that shown in FIGS. 10A-10C, acts as a piston and creates suction as the obturator is pulled through the outer thin-walled tube.

In another embodiment, the O-ring may be placed about 2.5 cm from the tip, the brush extends about 1.5 cm from the tip, and there is about 1 cm of bare wire between them.

As shown in FIGS. 9, 10 and 11, a skirt stop is provided around the outer surface of the thin-walled tube near the distal end, and the skirt stop may be in a fixed position or manually slidable. Good too. The skirt is approximately 1 cm in diameter and may be made of nylon, polyurethane, silicone, neoprene, or other medically acceptable plastic or rubber. Typically, the skirt is fixed in place and either glued (eg, UV-cured methyl methacrylic adhesive) or molded into place on the cannulation.

The biopsy device is used as follows. (a) Fully retract the brush into the external cannulation. (b) Insert the cannula into the cervix through the vagina until the skirt stopper reaches the external os of the cervix. The tip of the brush must be offset from the base. (c) Pull the lateral cannula backward until it stops, ie, until it abuts the handle. Next, rotate the brush by turning the handle while holding the intubation. For example, rotate the brush clockwise until the fiducial mark on the handle indicates the completion of one 360° rotation, then counterclockwise until the fiducial mark on the handle indicates the completion of one -360° rotation. You can also rotate it. Alternatively, the rotating brush may be rotated in only one direction by rotating 360° four or five times. In some cases, the brush position may be changed axially, but the brush should not be withdrawn into the cannulation until sample collection is complete. (d) After sampling with the brush, pull the guidewire by the handle until the cannula hits a stop (eg, the edge of the handle), thereby drawing fluid around the tip into the cannula, and then draw the brush into the cannula. (e) After withdrawing the device from the vagina, the sample is brushed by immersing the brush and the fluid in the cannula in a cell preservation solution such as formalin and moving the brush in and out of the fluid-soaked cannula. Wash out into preservation solution.

The invention can be used, for example, to sample the interior of the uterus in order to diagnose abnormalities. Thereby, cancer can be detected or removed. This allows sufficient tissue samples to be obtained to determine the cause of infertility.

Anal brushes are also adopted. Such biopsy devices typically have shorter cannulation and guidewires than endocervical brush biopsy devices because they are more anatomically accessible. For example, the cannula may be 10 cm to 15 cm in length, and the brush may extend 2 cm to 6 cm beyond the end of the cannula. Similar to the cervical brush biopsy device described above, a skirt is preferably provided to prevent insertion of the cannula beyond the cannula into the anus to provide a physical reference distance for insertion. In some cases, the skirt may be repositioned over the intubation to allow the physician to determine how deep the insertion depth should be to take the sample. This readjustment requires more force than would be applied by applying non-forced compression of the intubation against the skirt stop, so that it maintains its position during use, but the biopsy device When it is outside the body, it is advantageous because it can overcome the stiction force.

A rough absorption tip may be provided to scrape the uterine surface and absorb the fluid sample during the biopsy.

Example 2: According to a second embodiment, a multi-sample biopsy device is provided that is capable of acquiring and separating multiple biopsy samples taken at one time. This therefore requires multiple biopsy brushes or instruments and multiple intubations to extend and retract the instruments therein.

As mentioned above, an insertion depth position reference such as a skirt stop may be provided. However, if the multiple biopsy instrument system has a mechanism maintained outside the opening, the diameter of the instrument may be large enough to act as a stop without additional structure.

According to one design, each biopsy instrument, including the intubation and guidewire control mechanisms, is separate. A set of biopsy instruments are grouped together within one outer tube housing. The tube has a conical internal contour at the distal end so that a single biopsy instrument can be advanced beyond the end of the housing and into the opening or tube section where biopsy tissue is collected. In some cases, endoscopic guidance of the biopsy may be desired, in which case a second cannulation supporting the endoscope and illumination may also be advanced. Endoscopic intubation may inject magnesium for visualization, but this is not preferred for brush biopsies because the magnesium washes away dislodged cells and reduces the positional accuracy of sample collection. Inert gases such as CO ₂ may also be injected through the cannulation in a known manner. The one or more instruments may have a rough absorbent tip to scrape the uterine surface and absorb fluid sample during biopsy.

For example, a biopsy brush may be provided within a 3 mm tube with six separate brushes within the housing. A stop may be provided at the proximal end of each cannula within the housing to prevent over-retraction. Marks may be placed on each intubation to inform the physician regarding insertion depth. In some cases, the physician may wish to perform stepwise sampling at a series of depths within the orifice, and each intubation may have a stop that limits the depth of insertion, providing a tactile sensation to the physician when the depth is reached. This is advantageous because it provides feedback. This stop may be a simple O-ring or clamp and is adjusted by the physician on each biopsy sampling device prior to the procedure. The guide wire of each sampling device may also have a depth limit. Of course, the retracted position with the biopsy instrument fully retracted into the cannula represents one extreme, and in order to control how far the guidewire is extended beyond the end of the cannula, A clamp or limiter may be provided at the operating end.

In this first design, each biopsy brush may be of a known type, with the optional addition of an insertion limiter and a retraction limiter, and an optional absorption tip, and indeed multiple biopsy specimens. The housing itself for arranging the collection session may be provided independently of the biopsy brush. It should be noted that the absorption structure need not be at the extreme tip, and in fact may be displaced in some cases. Generally, a larger housing diameter eliminates the need for a separate skirt stop, although the housing may terminate in a skirt stop.

Example 3: According to a second design of a multiple sample biopsy device, a single manipulator extends from the housing and itself houses multiple biopsy instruments.

As mentioned above, an insertion depth position reference such as a skirt stop may be provided. However, if the multiple biopsy instrument system has a mechanism maintained outside the opening, the diameter of the instrument may be large enough to serve as a stop without additional structure.

Accordingly, selectively engageable couplings are provided between a single guidewire and various instruments. Couplings couple guidewires that extend to a physician manipulation interface, such as a gripping element, handle, or pivot mechanism, to the individual guidewire of each instrument. Advantageously, the plurality of instruments are provided in a rotating barrel that serves as a housing. Each biopsy instrument, once engaged with a manipulation guidewire, can be advanced an insertion distance with its respective cannulation, and the biopsy head then advanced past the cannulation, twisted or otherwise A biopsy sample can be obtained by operating the The biopsy head is then pulled back into the cannulation, then the sheath with the covered biopsy head is pulled back into the cartridge, the barrel is twisted, and another biopsy instrument may then be engaged. .

Thus, the coupling is a coaxial coupling that separately couples and controls the cannula and the guidewire within each cannula. For example, the cannulation end within the cartridge may terminate with a magnetically permeable steel ring. In this way, magnetic coupling can be used for connecting and disconnecting cannulation. The inactive biopsy device may also be held in place by another magnet, typically an electromagnet or a permanent magnet with an electromagnetic release. The guidewire can be selectively connected to an externally manipulated guidewire by a spring loaded clamp. Rotating the barrel releases the spring-loaded clamp and, upon reaching the next detent position, re-engages the next biopsy instrument aligned with the spring clamp. Within the barrel, guidewires from the biopsy instruments extend beyond the proximal end of each cannula.

The barrel is typically at least as long as the desired insertion depth of cannulation into the patient. Thus, if it is desired to have an insertion depth of 12 cm, the barrel mechanism may be 13 cm to 16 cm long.

As shown in FIG. 14, a plurality of similar brushes are provided within the cartridge. In Figure 15, a plurality of different brushes are provided within the cartridge. The cartridge has an outlet for an engaged biopsy instrument. Each brush has its own associated cannula, which can be independently advanced into the patient depending on which instrument is engaged. Mechanisms at the proximal end of the housing determine the angle of rotation, latching the respective actuating instrument to the intubation instrument advancement control mechanism, clamping the guidewire of the respective actuating instrument to the guidewire control mechanism for manipulation by the physician; and possibly other controls such as cannulation deflection angle to control barrel position selection.

FIG. 16 shows an end view of a portion of the mechanism within the barrel where one guidewire is freely manipulated by the physician while being locked from access for manipulation of the other guidewire.

Figure 14 shows a bulb located in close proximity to each sampling brush that is arranged to draw a sampling vacuum when the respective brush is pulled back into the cannula.

In FIG. 15, only one biopsy device has such a feature. The biopsy sampling device may be, for example, an endocervical sampler, an endometrial sampler, a punch sampler, and an endometrial sampler with suction.

In some cases, the cannulation itself may be bendable or angularly navigable to direct the biopsy instrument to the desired area. Flexible cannulation may be uniaxial, i.e., typically as a result of tension on a tension element, such as a cable, guide wire or filament (not shown) attached to the wall of the cannulation. It may be curved at the end. Controlling the angle of curvature and the angle of rotation of the cannulation relative to the organ provides a reasonable range of control. Similarly, punches, or snares, or encapsulated biopsy devices can also be controlled by tension, which may be wires or polymer filaments. Therefore, a single guidewire with a single degree of freedom (advancement/retraction) is the simplest case, and additional controls and degrees of freedom may be provided. Note that SMA actuators may also be used to change the tension. Control mechanisms for these instruments may be selectively engaged via mechanisms or may be provided individually to the user.

An endoscopic imaging device (not shown) may be provided, preferably as a feature in the housing, for use with various biopsy instruments within the housing. For example, a 1 mm to 3 mm endoscopic camera with fiber optic illumination or direct LED illumination may be provided, such as an On Semiconductor OVM6946 1/18'' 400×400 imager.

Example 4: Figure 18 shows a side perspective view of a prototype biopsy device with absorbent sponge material at the distal tip of the biopsy device. A longer foam tip allows more liquid absorption but requires a shorter brush for the same length of device. The foam may have a length of 0.25 inches. The absorbent foam tip is positioned over the acrylic ball at the end of the guidewire, which is free of bristles over the length of the foam. The foam may be attached to the brush by using FEP heat shrink to compress the proximal end of the foam and applying UV adhesive (Loctite 4011 or 4306 or AA3979) before removing the heat shrink.

The outer diameter of the cannulation is 0.150 inches. When retracted, the maximum fluid sample by vacuum was 0.51 ml. The volume absorbed by the foam tip was 0.03-0.05 ml for water and 0.62-0.72 ml for 5000 cSt fluid.

The brush may be a straight natural 6-12 nylon filament on a 304SS core terminated with an acrylic ball. The brush torsion wire is welded to the proximal core wire of the brush. The dimensions of the preferred embodiment are as follows.
Overall Length: 12" ± 0.125", Distance from Tip to Bristles: 0.25" Core Wire 304SS, Spring Tempered, Diameter: 0.018", Twisted Wire 304SS Diameter 0.037" Brush Diameter : 0.118" ± 0.010", Brush Length: 1.25" ± 0.125" Bristles Straight Natural 6-12 Nylon Filament 0.003" Single Stem/Single Spiral, 45° from Core Wire Angling of the acrylic bulb at the tip: 0.055" ± 0.015" diameter. The handle is e.g. textured with a concave contour, ergonomically shaped, Tecoflex 60D with 20% _BaSO4 , long It is approximately 1.5 inches long and 0.313 inches in diameter.

The skirt comprises polycarbonate (Caliber 2061) or silicone, 0.787 inch diameter, 0.742 inch length, biconic cross profile with 30° and 60° angles, and smooth edges.

Nusil Med-360 silicone fluid 1000 cP may be used to lubricate the cannulation and seal the vacuum mechanism. The plunger for drawing the vacuum was made of NuSil-4970 silicone, 0.118 inches long and 0.135 inches in diameter, with a sealing surface at each end with a central recess. The plunger is a compression fit around the wire proximal to the brush.

The foam tip is, for example, urethane foam obtained from a Puritan 1135 Purswab® foam tip applicator (Puritan Medical Products Co., Guilford, Maine, USA) in the prototype, but in practice it is custom-made. It is.

The device is designed to maximize cell collection during the biopsy process at the doctor's office. This combines the built-in suction process and absorption created by the sponge with the overall destruction of the endometrium using the brush. A series of tests made it possible to select the most suitable brush. It has a smaller diameter compared to its competitors (0.118 inch ± 0.010 inch and 1.25 inch ± 0.125 inch length), providing satisfactory tissue sampling while promotes reduction of discomfort.

After tissue disruption is complete, the sponge tip absorbs additional fluid and material and the device creates a vacuum that draws additional tissue sample into the device cannula. The idea of suction is different from the suction used in other devices. The suction does not obtain tissue directly from the uterine wall, but rather suctions tissue that has been previously scraped from the uterine wall by a brush, ensuring a better patient experience. The sponge tip prevents puncture of the uterine wall and provides additional tissue collection and fluid intake through absorption. A guard (eg, made of polycarbonate) is placed on the neck during the procedure to prevent over-insertion of the device.

The treatment is as follows.
1. Treatment: Place the patient in the lithotomy position, generally as shown in Figure 21A. Gradually insert the speculum and open it to expose the cervix. FIG. 21A shows a side view of the vaginal canal/uterus in cross section. Only the outline of the patient's skin and labia, vagina, cervix, and uterus are depicted. The position of the pelvis and legs suggests that the patient is in the examination position.
2. Make sure the brush is fully retracted into the external cannulation.
3. Insert the external cannulation of the device gradually into the uterus through the cervix and stop when the skirt (guard) contacts the cervix. (Figure 21B)
4. Stretch the brush by gradually pushing the handle until the resistance at the tip reaches the base. (Figure 21C)
5. Rotate the sampler clockwise, completing 4-5 360° rotations.
6. A sponge on the tip protects the base from puncturing. It results in additional tissue sampling by absorption of fluid and cells from the uterus.
7. Pull the handle back. Suction generated by a plunger located inside the cannula provides aspiration of cells and prevents loss of sample from the brush.
8. Immediately immerse the sample in the preservative solution. See FIG. 7 or FIG. 19.
9. Handle specimens and brushes according to pathology laboratory instructions.

Figure 18 shows details of the tip of the biopsy brush, with a sponge located at the tip of the device and distal to the brush to cushion the tip and provide volume for sampling cell-containing fluid from the endometrium. I will provide a.

FIG. 19 shows a specimen collection container with a pocket for holding a biopsy brush, eg, after it has been cut or severed from a complete biopsy device. The specimen collection container may have an RFID, barcode, or 2D barcode (or QR code) for identification. In some cases, the RFID is transferred from the complete biopsy device to a sample collection container with a biopsy brush portion. The pockets are tamper-proof and may therefore provide enhanced security and authentication throughout the transportation chain.

Claims (51)

A flexible coaxial tissue sampling device comprising:
an intubation having a wall and a hollow space inside the wall;
a displaceable wire within the hollow space, the displaceable wire having a first end extending from the proximal end of the cannula in a first state and a distal end of the cannula in a second state; a displaceable wire having a second end configured to be retracted into the distal end of the cannula;
The second end of the displaceable wire includes a suction element, a cell sampling structure, and a porous absorbent material, the cell sampling structure and porous absorbent material being in the intubation state in the first state. and in the second state is inside the cannulation, the suction element being proximal to the cell sampling structure and the porous absorbent material;
The flexible coaxial structure is such that tension on the first end of the displaceable wire at the proximal end of the cannulation results in retraction of the displaceable wire from the first state to the second state. , causing a displacement of the displaceable wire into the cannula and a corresponding proximal displacement of the aspiration element, the cell sampling structure, and the porous absorbent material, causing the medium outside the cannula to flow into the cannula. the porous absorbent material configured to retain a fluid sample obtained in the first state after transition to the second state; Flexible coaxial tissue sampling device. The tissue sampling device of claim 1, wherein the porous absorbent material caps the second end of the displaceable wire to protect tissue from damage by the tip of the displaceable wire. The tissue sampling device of claim 1, wherein the porous absorbent material is formed at a tip of the second end of the displaceable wire. The porous absorbent material within the cannula in the second state absorbs a biopsy sample within the cannula obtained during the transition from the first state to the second state at the distal end from the patient. 2. The tissue sampling device of claim 1, wherein the tissue sampling device protects from contamination during withdrawal. The tissue sampling device of claim 1, wherein the porous absorbent material is adapted to absorb biopsy samples for nucleic acid analysis. The tissue sampling device of claim 1, wherein the porous absorbent material is a sponge. The tissue sampling device of claim 1, wherein the cell sampling structure includes a brush. 8. The tissue sampling device of claim 7, wherein the brush includes a plurality of bristles extending radially from the displaceable wire. The coaxial structure is configured to be inserted through the internal cervical ostium of a human uterus to remove an endometrial biopsy sample, and sliding a depth stop on the cannulation causes the coaxial structure to The tissue sampling device of claim 1, having an adjustable depth during a biopsy procedure while maintained in the first state. 2. The coaxial structure of claim 1, wherein the coaxial structure is configured to be inserted through the internal cervical os of a human uterus to a predetermined depth and withdrawn from the cervix to retrieve an endometrial biopsy sample. Tissue sampling device. The coaxial structure is
inserted into the cervical os to a predetermined depth with the displaceable structure in the second state;
the cell sampling structure is stretched to the first state while in the uterus;
operated by a user by movement of the first end of the displaceable structure to remove cells within the uterus;
retracted to the second state within the uterus to create a vacuum to draw a liquid sample around the cell sampling structure into the distal end of the cannulation;
11. The tissue sampling device of claim 10, further configured to be retracted from the cervical os with the displaceable structure in the second state. 2. The tissue sampling device of claim 1, wherein the cell sampling structure comprises a spiral twisted steel wire with extending bristles welded to a proximal guidewire. 13. The tissue sampling device of claim 12, wherein the porous absorbent material comprises urethane foam disposed on the second end and over a cap terminating the spiral twisted steel wire. The tissue sampling device of claim 1, wherein the cannula has an outer diameter of about 0.15 inches and a length of 20-50 cm. a slidable skirt stopper disposed on an outer surface of the flexible cannula, the skirt stopper being configured to prevent insertion of the flexible cannulae into the uterus of a patient beyond the axial position of the skirt stopper; The tissue sampling device of claim 1, further comprising: a tissue sampling device according to claim 1; at least two flexible coaxial structures, each having a respective cannulation, a respective displaceable wire, a respective suction element, a respective cell sampling structure, and a respective porous absorbent material. one flexible coaxial structure;
When engaged, tension and compression are transmitted from the user interface to the displaceable structure to cause the displaceable structure to transition between the first state and the second state, and when disengaged. selectively engaging and disengaging a respective displaceable wire of a respective flexible structure with the user interface such that tension and compression are not transferred from the user interface to the displaceable structure; 2. The tissue sampling device of claim 1, comprising: a housing configured to . The tissue sampling device of claim 1, further comprising an electric motor configured to move the displaceable structure. A flexible coaxial tissue sampling device comprising:
an intubation having a wall and a hollow space inside the wall;
a displaceable wire within the hollow space, the displaceable wire having a first end extending from a proximal end of the cannula in a first state and a distal end of the cannula in a second state; a displaceable wire having a second end configured to be retracted into the distal end of the cannula;
the second end of the displaceable wire includes a cell sampling structure and a porous absorbent material, the cell sampling structure and the porous absorbent material being outside the cannulation in the first state; and is inside the intubation in the second state;
The flexible coaxial structure is configured such that tension on the first end of the displaceable wire at the proximal end of the cannulation results in retraction of the displaceable wire from the first state to the second state. causing displacement of the displaceable wire, the cell sampling structure, and the porous absorbent material into the cannulation such that the porous absorbent material is in the first state after transitioning to the second state. a flexible coaxial tissue sampling device configured to hold a fluid sample obtained in a state and protect tissue from contact with the second end of the displaceable wire. a brush in which the cell sampling structure has a plurality of bristles extending radially from the displaceable wire and terminating in the porous absorbent material including an atraumatic bulb covered by a layer of open cell foam; including;
further comprising a suction element displaceable with the displaceable wire and proximal to the cell sampling structure and the porous absorbent material, the suction element displacing the displaceable wire when the displacement wire is withdrawn into the cannulation. 19. The tissue sampling device of claim 18, configured to create a negative pressure within the cannula distal to a suction element. A biopsy method comprising:
an intubation having a wall and a hollow space within the wall, a displaceable wire within the hollow space, the displaceable wire having a first end extending from a proximal end of the cannula; and a second end configured to extend from the distal end of the cannula and be retracted into the distal end of the cannula in a second state. the second end of the displaceable wire includes a cell sampling structure and a porous absorbent material, the cell sampling structure and the porous absorbent material; is outside the cannulation in the first state and inside the cannulation in the second state;
while the flexible coaxial structure is in the second state, inserting the distal end of the cannula through the cervix, beyond the internal cervical ostium, and into the uterus;
forcing the first end of the displaceable wire into the cannulation to cause the flexible coaxial structure to assume the first state;
rubbing the cell sampling structure against the endometrium while protecting the endometrium from invasion by the tip of the displaceable wire and absorbing fluid into the porous absorbent material to obtain a cell sample; manipulating the displaceable wire;
Tension is applied to the first end of the displaceable wire at the proximal end of the cannulation to bring the displaceable wire into the first state while retaining the absorbed fluid within the porous absorbent material. retracting the displaceable wire, the cell sampling structure, and the porous absorbent material into the cannulation;
capping the distal end of the cannulation with the porous absorbent material to prevent contamination of the biopsy sample retained on the cell sampling structure by cells within the cervix and vagina; including biopsy methods. A tissue sampling device comprising: a flexible cannula comprising a coaxial structure, the coaxial structure having at least a distal end configured to maintain an internal vacuum; and a displaceable structure within the cannula. , wherein the displaceable structure has a first end extending from the proximal end of the cannula in a first state and a second end extending from the distal end of the cannula in a second state. a second end configured to be retracted into the displaceable structure, the second end of the displaceable structure having a cell sampling structure preceded by a proximal suction element. and the coaxial structure has a porous absorbent material, and the coaxial structure is configured such that tension on the first end of the displaceable structure at the proximal end of the cannulation changes from the first state of the displaceable structure to the first state of the displaceable structure. A tissue sampling device configured to cause retraction to the second state to generate suction that displaces media external to the cannulation into the cannula distal of a piston. 22. The tissue sampling device of claim 21, wherein the porous absorbent material is formed at the distal tip of the second end. 22. The tissue sampling device of claim 21, wherein the porous absorbent material is adapted to absorb biopsy samples for nucleic acid analysis. 22. The tissue sampling device of claim 21, wherein the porous absorbent material is a sponge. 22. The tissue sampling device of claim 21, wherein the porous absorbent material is a sponge formed at the distal tip of the second end. 22. The tissue sampling device of claim 21, further comprising a pump configured to create a negative pressure within the cannulation distal end to draw a fluid biopsy sample therein. 22. The tissue sampling device of claim 21, wherein the cell sampling structure includes a brush. 28. The tissue sampling device of claim 27, wherein the brush includes a plurality of bristles extending radially from the displaceable structure. 28. The tissue sampling device of claim 27, wherein the brush has a helical cross-sectional profile. 22. The coaxial structure of claim 21, wherein the coaxial structure is configured to be inserted into the internal cervical os of a human uterus to a predetermined depth and withdrawn from the cervix to retrieve an endometrial biopsy sample. Tissue sampling device. The coaxial structure is
inserted into the cervical os to a predetermined depth with the displaceable structure in the second state;
the cell sampling structure is stretched to the first state while in the uterus;
operated by a user by movement of the first end of the displaceable structure to remove cells within the uterus;
retracted to the second state within the uterus to create a vacuum to draw a liquid sample around the cell sampling structure into the distal end of the cannulation;
31. The tissue sampling device of claim 30, further configured to be retracted from the neck while the displaceable structure is in the second state. 22. The tissue sampling device of claim 21, wherein the cell sampling structure comprises a spiral twisted steel wire with extending bristles welded to a proximal guidewire. 33. The tissue sampling device of claim 32, wherein the porous absorbent material comprises urethane foam disposed distal to the second end and disposed over a cap terminating the spiral twisted steel wire. . 22. The tissue sampling device of claim 21, wherein the cannula has an outer diameter of about 0.15 inches and a length of 20-50 cm. 22. The method of claim 21, further comprising a skirt stop disposed on an outer surface of the cannula configured to prevent insertion of the cannula into the uterus of a patient beyond an axial position of the skirt stop. Tissue sampling device. the skirt stopper includes a flange-like element on an outer surface of the cannula, the cannula being configured to be inserted into the internal cervical canal of a human uterus to the predetermined depth;
inserting the displaceable wire in the second state into the internal cervical os to the predetermined depth;
The cell sampling device is extended to the first state while in the uterus,
operated by movement of the first end of the displaceable wire to remove endometrial cells;
retracting to the second state within the uterus and drawing a vacuum around the cell sampling device to draw a liquid sample into the distal end of the cannulation;
36. The tissue sampling device of claim 35, further configured to be retracted from the cervical os with the displaceable wire in the second state. a plurality of flexible cannulae, each having at least a distal end configured to maintain an internal vacuum;
each of the displaceable structures within each flexible cannula forming a set of coaxial structures;
When engaged, tension and compression are transmitted from the user interface to the displaceable structure to cause the displaceable structure to transition between the first state and the second state, and when disengaged, the displaceable structure transitions between the first state and the second state. 22. A housing configured to selectively attach a respective displaceable structure to the user interface such that tension and compression are not transferred from the user interface to the displaceable structure. Tissue sampling device as described. 22. The tissue sampling device of claim 21, further comprising an electric motor configured to axially displace the displaceable structure. 22. The tissue sampling device of claim 21, further comprising an electric motor configured to rotate the cell sampling structure. A multiple sample biopsy device, the device comprising:
multiple flexible intubations;
a displaceable structure within each intubation forming a coaxial structure, the structure comprising:
Each displaceable structure has a first end extending from the proximal end of the cannula, and a first end extending from the distal end of the cannula in a first state and within the distal end of the cannula in a second state. a second end configured to be retracted;
a displaceable structure, wherein the second end of the displaceable structure has a cell sampling structure distally terminated in porous absorbent foam;
When engaged, tension and compression are transmitted from the user interface to the displaceable structure to cause the displaceable structure to transition between the first state and the second state, and when disengaged. a housing configured to selectively attach a respective displaceable structure to the user interface such that tension and compression are not transferred from the user interface to the displaceable structure. Inspection equipment. A method for collecting a tissue sample, the method comprising:
providing a coaxial structure, the coaxial structure comprising: a flexible cannula having at least a distal end configured to maintain an internal vacuum; and a displaceable structure within the cannula; wherein the displaceable structure has a first end extending from the proximal end of the cannula in a first state and a first end extending from the distal end of the cannula in a second state; a second end configured to be retracted into the displaceable structure, the second end of the displaceable structure being preceded by a piston and terminated by a porous absorbent tissue scraping structure. comprising a cell sampling structure;
applying tension to a first end of the displaceable structure at the proximal end of the cannulation to retract the displaceable structure from the first state to the second state to create a vacuum; A tissue sampling method, including: 42. The method of claim 41, wherein the coaxial structure further includes a skirt around the flexible cannula configured to limit insertion depth of the flexible cannula into a human neck. The coaxial structure is inserted into the internal cervical os of a human uterus to the predetermined insertion depth defined by the axial position of the skirt around the flexible cannulation for removing an endometrial biopsy sample. 43. The method of claim 42, wherein the method is configured to be inserted and withdrawn from the cervix. inserting the distal end of the coaxial structure into the cervical ostium of the uterus to a predetermined depth, with the displaceable structure in a second state;
extending the distal end of the coaxial structure to the first state while the cell sampling structure is within the uterus;
manipulating the first end of the displaceable structure to remove cells within the uterus;
retracting the coaxial structure within the uterus to the second state to create a vacuum to draw a liquid sample around the cell sampling structure into the distal end of the cannulation;
44. The method of claim 43, further comprising retracting the distal end of the coaxial structure from the neck in the second state. 41. The cell sampling structure comprises a brush having a plurality of bristles extending radially from the displaceable structure and terminating in an atraumatic bulb covered by an open cell foam layer. The method described in. the cell sampling structure includes a spiral torsionally flexible wire with extending bristles, and the method includes twisting the guidewire thereby rotating the cell sampling structure; 42. The method of claim 41. A flexible coaxial biopsy device comprising:
a tubular cannula having a wall configured to maintain an internal vacuum relative to the exterior of the tubular cannula having a displaceable wire within the tubular cannula;
A cell sampling device distally terminated with a porous absorbent structure, wherein each of the cell sampling device and the porous absorbent structure are configured to disrupt a surface of tissue; attached to the displaceable structure of the tubular cannula when the displaceable element is disposed in a first state and protrudes from the distal end of the tubular cannula when the displaceable element is disposed in a second state. a cell sampling device configured to be housed within the distal end of the cannulation. 48. The flexible coaxial biopsy device of claim 47, further comprising a flange-like element on an outer surface of the tubular cannula configured to limit the depth of insertion of the tubular cannula into the cervix. the cell sampling device includes a plurality of bristles extending outwardly from the displaceable wire and terminating at the distal ends in an atraumatic bulb covered by the porous absorbent structure including a foam layer; 48. A flexible coaxial biopsy device according to claim 47. The endometrial biopsy sample is inserted into the internal cervical os of the human uterus to a predetermined depth to remove the endometrial biopsy sample from inside the uterus, and after the endometrial biopsy sample is obtained, it is pulled out from the external cervical os of the uterus. 48. The flexible coaxial biopsy device of claim 47, configured to. 48. The flexible coaxial biopsy device of claim 47, further comprising an element that creates a negative pressure within the tubular cannula when the displaceable wire is retracted into the tubular cannula.

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