Cardiac tissue sampling device

Abstract

In accordance with the concepts of the present invention, a tissue sampling device and method are provided. In various embodiments, the tissue sampling device and method are cryobiopsy tissue sampling devices and methods. The cryobiopsy device may be a cardiac cryobiopsy device that includes an intravenous probe having at least one tip capable of reaching a temperature sufficient to freeze tissue such that the tissue adheres to the tip. The tip preferably remains at a freezing temperature during withdrawal of the probe, allowing the attached tissue to be collected for its intended post-extraction purpose.

Description

Technical Field

[0001] The concept of the present invention relates to the field of tissue sampling in organisms, and is particularly useful for tissue sampling in living mammals.

Background Art

[0002] Cross-reference to Related Applications This patent application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 122,712, filed on December 8, 2020, under the U.S. Patent Law. The entire above-mentioned U.S. Provisional Patent Application is incorporated herein by reference.

[0003] In various medical diagnostic, treatment, and research contexts, the ability to sample tissue for examination and analysis is particularly useful. As examples, clinical uses of tissue sampling in the cardiovascular field include, but are not limited to, examination of tissue from transplant recipients to evaluate possible rejection reactions, and diagnosis of various diseases such as cardiac sarcoidosis, amyloidosis, subtypes of myocarditis, and intracardiac tumors. As a further example, research uses of tissue sampling include, but are not limited to, transcriptomics - multiple cells and single cells, and transcriptomics of cardiac biopsies in Das 2019 - CABG patients → HFpEF.

[0004] In 1972, Caves modified the endomyocardial biopsy so that it could be used through the right internal jugular vein. This modification allowed the bioptome to be inserted percutaneously, but the large diameter of the bioptome head required the use of a large (valveless) sheath, and the patient was at risk of bleeding or air embolism during bioptome insertion or removal. This technique provided several advantages, including percutaneous insertion, use of local anesthetics to minimize patient discomfort, rapid operation, direct entry of the bioptome into the right ventricular apex, and repeated insertion and removal through the same sheath.

[0005] Subsequently, Caves introduced a Stanford modification to the earlier Konno bioptom. The Stanford (or Caves-Shulz) bioptom included two hemispherical cutting jaws with a total diameter of 3 mm (9F) attached to the tip of a catheter. One jaw remained stationary, while the other opened and closed under the control of a mosquito forceps at the proximal end of the catheter used to extract tissue. A spring-loaded adjustable nut allowed the operator to control the amount of force applied by opening and closing the surgical forceps. This bioptom was reusable and required careful cleaning after each use, eventually necessitating re-instrumentation and sharpening of the jaw edges after 50 procedures.

[0006] However, the aforementioned devices and techniques have significant limitations. For example, the use of bioptome catheters carried a 0.54% risk of serious complications such as perforation. This risk increased when the interventricular septum was not sampled. Furthermore, the jaws tended to crush the tissue being sampled, potentially negatively impacting transbronchial lung cryobiopsy, which is used to sample lung tissue in the diagnosis of lung disease. This technique is performed by advancing the probe to the periphery of the lung through the working channel of a bronchoscope. The probe tip is rapidly cooled until a cryogenic adhesion occurs between the tip and the adjacent lung tissue. The tissue sample is extracted by forcefully pulling the probe tip. The probe is then removed from the airway along with the bronchoscope.

[0007] Cryobiopsy had not been used to sample cardiac tissue. Sampling intraventricular cardiac tissue, which cannot be done simply through the airway, presents problems not encountered with lung cryobiopsy. It would be particularly beneficial if only tissue cells could be removed from the heart wall, minimizing damage compared to the attachment and removal of tissue clumps detached from the lung wall. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] U.S. Patent Application Publication No. 2013 / 165915 [Patent Document 2] U.S. Patent Application Publication No. 2016 / 066896 [Patent Document 3] International Publication No. 2019 / 168634 [Overview of the project] [Means for solving the problem]

[0009] According to one aspect of the concept of the present invention, a cardiac cryobioplasty method includes a number of steps, such as: introducing a cryoprobe (or cryogenic probe) into the ventricle of the body through a blood vessel connected to the heart; maneuvering the tip of the probe to a tissue sampling site within the ventricle; raising the sampling temperature of the probe tip to below freezing and maintaining contact until cardiac tissue or cells adhere to the probe tip from that site by freezing; and withdrawing the probe tip from the body while keeping the probe tip below freezing, thereby transporting the collected tissue from the ventricle to the outside of the body.

[0010] In some embodiments, the method further includes the step of raising the temperature of the probe tip above freezing point after it has been removed from the body to release the collected cardiac tissue or cells.

[0011] In some embodiments, the method further includes the step of removing the probe tip or a portion thereof from the probe while cardiac tissue or cells are attached to it, after the probe tip has been removed from the body.

[0012] In some embodiments, the cryoprobe includes an elongated catheter having a proximal end and a distal end. The distal end comprises a probe tip, and the proximal end comprises a refrigerant inlet port and a refrigerant outlet port. The method further includes the steps of introducing a refrigerant through the catheter to the probe tip via the inlet port to lower the temperature of the probe tip, and exhausting the refrigerant through the catheter shaft via the outlet port.

[0013] In some embodiments, the probe tip includes a microtube, and the method includes the steps of injecting a refrigerant as a liquid refrigerant into the probe tip, evaporating the refrigerant inside the probe tip to lower the temperature of the probe tip, and exhausting the refrigerant as a refrigerant gas from the probe tip.

[0014] In some embodiments, the method further includes the step of controlling the temperature of the probe tip by a controller comprising a processor.

[0015] In some embodiments, the probe tip includes at least one sensor coupled to a processor, and the method further includes the steps of sensing the temperature of the probe tip and / or the refrigerant entering and / or leaving the probe tip, and adjusting the probe tip temperature based on the sensed temperature.

[0016] In some embodiments, the method further includes the step of sensing the presence and / or absence of cardiac tissue or cells attached to the tip of the probe.

[0017] In some embodiments, the method further includes the step of establishing a feedback loop between at least one sensor and a controller so that the controller can monitor and adjust the temperature of the probe tip.

[0018] According to another aspect of the concept of the present invention, a cardiac cryobioplasty method is provided. The method includes the steps of introducing a cryoprobe into the ventricle of the body; maneuvering the tip of the probe to a tissue sampling site; bringing the tip of the probe to a sampling temperature below freezing and contacting the cardiac tissue at the tissue sampling site until cardiac tissue or cells adhere to the tip of the probe due to freezing; and withdrawing the tip of the probe from the body while maintaining the tip of the probe below freezing.

[0019] In some embodiments, the method further includes the step of raising the temperature of the probe tip above freezing point after the probe tip has been removed from the body, thereby releasing the collected cardiac tissue or cells from the probe tip.

[0020] In some embodiments, the method further includes the step of removing the probe tip or a portion thereof from the probe, with the collected cardiac tissue or cells still attached, after the probe tip has been removed from the body.

[0021] In some embodiments, the cryoprobe includes an elongated catheter having a proximal end and a distal end, the distal end comprising a probe tip, and the proximal end comprising a refrigerant inlet port and a refrigerant outlet port. The method includes the steps of introducing a refrigerant through the catheter to the probe tip via the inlet port to lower the temperature of the probe tip, and exhausting the refrigerant through the catheter shaft via the outlet port.

[0022] In some embodiments, the probe tip includes a microtube, and the method includes the steps of injecting a refrigerant as a liquid refrigerant into the probe tip, evaporating the refrigerant inside the probe tip to lower the temperature of the probe tip, and exhausting the refrigerant as a refrigerant gas from the probe tip.

[0023] In some embodiments, the method further includes controlling the temperature of the probe tip by a controller comprising a processor that controls the flow of refrigerant within the probe.

[0024] In some embodiments, the probe tip includes at least one sensor coupled to the processor, and the method includes sensing at least one state at the probe tip.

[0025] In some embodiments, at least one state at the probe tip is temperature and / or the presence of a tissue sample.

[0026] In some embodiments, the method further includes sensing the temperature of the probe tip and / or the refrigerant entering and / or exiting the probe tip using at least one sensor.

[0027] In some embodiments, the method further includes sensing the presence and / or absence of heart tissue or cells attached to the probe tip using at least one sensor.

[0028] In some embodiments, the method further includes sensing the presence and / or absence of heart tissue or cells attached to the probe tip using at least one sensor and using an optical sensor.

[0029] In some embodiments, the method further includes establishing a feedback loop between at least one sensor and the controller to enable the controller to monitor and adjust the probe tip temperature.

[0030] In some embodiments, the method further includes maintaining the probe tip temperature below freezing for at least 10 seconds, at least 30 seconds, or at least 1 minute after exiting the body.

[0031] In some embodiments, the method further includes the step of maintaining the probe tip temperature below freezing point after it has left the body, until user input received via the user interface instructs the controller to raise the probe tip temperature above freezing point.

[0032] In some embodiments, the method further includes the steps of sensing the ambient temperature outside the body and setting the probe tip temperature inside the ventricle based on the ambient temperature sensed outside the body.

[0033] In some embodiments, the method further includes the step of setting the probe tip temperature below freezing point based on the sensed ambient temperature and the duration for which the probe tip should be below freezing point outside the body.

[0034] According to another aspect of the concept of the present invention, a cardiac cryobioplasty apparatus or system is provided. The apparatus comprises a cryoprobe having a cryogenic probe tip and configured to be introduced into the ventricle through a blood vessel; a steering mechanism configured to steer the probe tip toward a tissue sampling site within the ventricle; and a controller equipped with a processor. The controller is configured to bring the probe tip to a sub-zero temperature to cause cardiac tissue and / or cells to adhere to the probe tip, and to maintain the temperature of the probe tip below freezing during withdrawal of the probe tip from the body to collect the attached cardiac tissue and / or cells.

[0035] In some embodiments, the controller is further configured to raise the temperature of the probe tip above freezing point after the probe tip has been removed from the body, thereby releasing the collected cardiac tissue or cells from the probe tip.

[0036] In some embodiments, the probe tip or a portion thereof can be detached from the probe with the collected cardiac tissue or cells attached after the probe tip has been removed from the body.

[0037] In some embodiments, the cryoprobe further comprises a proximal end having an inlet port and an outlet port, and at least one microtube configured to inject a liquid coolant received through the inlet port into the probe tip, the probe tip defining a chamber configured to receive the liquid coolant and transition the liquid coolant from a liquid state to a gaseous state to lower the probe tip temperature, and the probe defining a gas exhaust path from the probe tip to the outlet port.

[0038] In some embodiments, the controller is further configured to control the temperature of the probe tip.

[0039] In some embodiments, the probe tip includes at least one sensor coupled to a processor and configured to sense at least one state at the probe tip.

[0040] In some embodiments, at least one state at the probe tip is temperature and / or the presence of a tissue sample.

[0041] In some embodiments, the controller and at least one sensor are configured to sense the temperature of the probe tip, and / or the temperature of the refrigerant entering and / or leaving the probe tip.

[0042] In some embodiments, the controller and at least one sensor are configured to sense the presence and / or absence of cardiac tissue or cells attached to the probe tip.

[0043] In some embodiments, the controller and at least one sensor are configured to use an optical sensor to sense the presence and / or absence of cardiac tissue or cells attached to the probe tip.

[0044] In some embodiments, the device further includes a feedback loop between at least one sensor and a controller, allowing the controller to monitor and adjust the temperature of the probe tip.

[0045] In some embodiments, the controller is configured to maintain the probe tip temperature below freezing for at least 10 seconds, at least 30 seconds, or at least 1 minute after it has left the body.

[0046] In some embodiments, the controller is configured to maintain the probe tip temperature below freezing point after it has left the body, until user input received via the user interface instructs the controller to raise the probe tip temperature above freezing point.

[0047] In some embodiments, the controller is further configured to include an ambient temperature sensor and to set the probe tip temperature inside the ventricle based on the ambient temperature sensed outside the body.

[0048] In some embodiments, the controller is further configured to set the probe tip temperature below freezing point based on the sensed ambient temperature and the duration for which the probe tip should remain below freezing point outside the body.

[0049] The concept of the present invention will become clearer with consideration of the accompanying drawings and the following detailed description. The embodiments shown herein are provided as examples, not as limitations, and similar reference numerals represent the same or similar elements. The drawings are not necessarily to scale and are focused on illustrating aspects of the concept of the present invention. [Brief explanation of the drawing]

[0050] [Figure 1] This figure shows a conventional endoscopic cryoprobe. [Figure 2] This figure shows a cryoablation probe in the conventional technology. [Figure 3] This figure shows a cryobiops tissue sampling device according to a conceptual embodiment of the present invention. [Figure 3A] This figure shows an exemplary embodiment of a probe tip equipped with a tissue sensor according to a conceptual aspect of the present invention. [Figure 4] This is a flowchart of a cardiac cryobiopsy method according to an embodiment of the concept of the present invention. [Modes for carrying out the invention]

[0051] This specification will describe in more detail various aspects of the concept of the present invention with reference to the accompanying drawings, which show several exemplary embodiments. However, the concept of the present invention can be embodied in many different forms and should not be construed as being limited to the exemplary embodiments described herein.

[0052] In this specification, terms such as "first," "second," etc., are used to describe various elements, but it should be understood that these terms should not limit those elements. These terms are used to distinguish one element from another, not to suggest a required order of elements. For example, without departing from the scope of the invention, a first element may be called a second element, and similarly, a second element may be called a first element. As used herein, the term "and / or" includes any combination of one or more of the related enumerated items.

[0053] When we say that one element is "in," "connected to," or "joined" another element, it should be understood that the element may be directly in, directly connected to, or directly joined to the other element, or there may be an intervening element. In contrast, when we say that one element is "directly in," "directly connected to," or "directly joined" another element, there is no intervening element. Other words used to describe relationships between elements should be interpreted similarly (e.g., "between" and "directly between," "adjacent" and "directly adjacent").

[0054] The terms used herein are for the purpose of describing specific embodiments and are not intended to limit the invention. Where used herein, the singular form is intended to include the plural form unless the context clearly indicates otherwise. Furthermore, it should be understood that the terms “equipped,” “equipped,” “contains,” and / or “contains,” where used herein, specify the presence of the described features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0055] Spatially relative terms such as “downward,” “below,” “underside,” “upward,” and “above” may be used to describe the relationship between one element and / or feature and another, as shown in the diagram, for example. It should be understood that spatially relative terms are intended to encompass different orientations of the device in use and / or operation, in addition to the orientation shown in the diagram. For example, if the device in the diagram is turned upside down, the element described as “downward” and / or “below” another element or feature will be oriented “upward” of that other element or feature. The device may also be oriented in other ways (e.g., rotated 90 degrees or in other directions), and the spatially relative descriptions used herein will be interpreted accordingly.

[0056] In this specification, exemplary embodiments are described with reference to schematic cross-sectional views of idealized exemplary embodiments (and intermediate structures). Therefore, deformations from the illustrated shapes may be expected, for example, due to manufacturing techniques and / or tolerances. Accordingly, exemplary embodiments should not be construed as being limited to the specific shapes shown herein, and should include deviations in shape resulting from, for example, changes in manufacturing or reasonably foreseeable changes.

[0057] To the extent that functional features, operations, and / or steps are described herein or understood to be included in various embodiments of the concept of the present invention, such functional features, operations, and / or steps can be embodied in functional blocks, units, modules, operations, and / or methods. Furthermore, to the extent that such functional blocks, units, modules, operations, and / or methods include computer program code, such computer program code can be stored in a computer-readable medium, such as non-temporary memory and media, which is executable by at least one computer processor.

[0058] According to the concept of the present invention, a tissue sampling apparatus and method are provided. In various embodiments, the tissue sampling apparatus and method is a cryobiops tissue sampling apparatus and method. In various embodiments, the cryobiops apparatus can be used as a cardiac cryobiops (or cryogenic biopsy) apparatus to sample cardiac tissue. In various embodiments, the cryobiops apparatus can be used to sample tissue from other organs or parts of the body, such as the stomach, kidneys, liver, spleen, intestines, brain, and / or reproductive system.

[0059] Cardiac cryo-biopsy devices can be used to excise clusters of tissue cells, which may consist of a small number of tissue cells rather than relatively coarse clumps of cardiac tissue, thereby minimizing damage and destruction to cardiac tissue at the sampling site. Therefore, the sampled tissue (or harvested tissue) may contain a small number of tissue cells from the sampling site.

[0060] In various embodiments, a cryobiopss device may include an intravenous probe having at least one probe tip capable of reaching a temperature sufficient to freeze tissue or cells so that they adhere to the tip. The tip preferably remains at freezing temperature during probe withdrawal and can retain the adhered tissue sample on the probe tip throughout the entire withdrawal or removal process, at least from the sampling site to the point where it leaves the body or beyond, and the collected sample can be gathered for its intended purpose. In some embodiments, the temperature of the probe tip is selectively maintained below freezing point even after the point where it leaves the body, until, for example, a clinician raises the temperature of the probe tip above freezing point to release the tissue sample from the probe tip.

[0061] In some embodiments, the temperature of the probe tip can be kept sufficiently low so that its temperature does not immediately rise above the freezing point at ambient room temperature. For example, in some embodiments, the temperature of the probe tip when it exits the body may be sufficiently below freezing so that the probe tip does not rise above the freezing point over a freezing time (t) after exiting the body. In some embodiments, t is at least 1 minute, at least 30 seconds, and / or at least 10 seconds. In some embodiments, a controller coupled to the probe may sense the ambient temperature using an ambient temperature sensor 20 outside the body and adjust the temperature of the probe tip to achieve a desired freezing time t after the probe tip is removed from the body.

[0062] Cryoablation probes are used to treat arrhythmias by ablating tissue within the heart, causing cardiac tissue to die through freezing (cell death). Several factors that influence cell death include freezing temperature, freezing rate, freezing duration, thawing rate, and repeated freezing. Mechanisms of cell death include direct cell damage, vascular failure, and / or immunological effects.

[0063] In such cryoablation systems, the tip of the probe is brought into contact with the endocardium and brought to a controlled freezing temperature. This freezing temperature is intended to freeze a portion of the inner wall of the heart to a predetermined depth necessary to kill the desired tissue in order to treat the arrhythmia. Once the treatment is complete and cell death has occurred, the tip of the probe is returned to a temperature above freezing point, and the probe is withdrawn through the catheter sheath used for insertion. No cardiac wall tissue is collected from the tip of the probe.

[0064] Unlike cryoablation, cryobiopsy is primarily intended to avoid cell death and is not a therapeutic treatment. According to the concept of this invention, cryobiopsy aims to excise a sample of living tissue cells for subsequent analysis and examination. Due to the diametrically opposed goals of cryoablation and cryobiopsy, their uses differ significantly, even if somewhat similar devices can be used for each. Furthermore, the setup and configuration of cryodevices may differ when used for different purposes. For example, a cryodevice (or system) may have a controller that implements a different set of logic and computer program instructions to achieve cryobiopsy rather than cryoablation. In some embodiments, different physical attributes and characteristics of a cryobiopsy device (or system) may exist compared to a cryoablation system, such as different sized probe tips and / or different materials used for the probe tips.

[0065] However, in some embodiments, when the appropriate logic for cryobiops is implemented, the same cryodevice can be used in a cryoablation procedure and then in a cryobiopsect procedure. For example, a cryoprobe can be advanced into the heart and used to perform cryoablation, and then the probe can be moved and used to perform cryobiopsect at the ablation site or another site in the heart, although cryoablation and cryobiopsect are different procedures.

[0066] In various embodiments, cryobiopsy is performed by freezing moist cardiac tissue at the sampling site onto the probe tip. In various embodiments, ice formation may occur at the tissue contact surface that causes the catheter probe tip to adhere to the tissue. The catheter with the sampled tissue is withdrawn while the tissue sample is still attached to the probe tip, and the probe tip remains below freezing point during withdrawal.

[0067] Figure 1 shows a conventional endoscopic cryoprobe. Figure 2 shows a conventional cryoablation probe.

[0068] Examples of cryoprobes that can be used for cryobiopsies include, but are not limited to, various flexible cryoprobes offered by Erbe, such as those with diameters of 1.1 mm, 1.7 mm, 1.9 mm, and 2.4 mm used for endoscopy, as shown in Figure 1, and the Freezor® 2 cardiac catheters 4 / 6 / 8 mm offered by Medtronic for cryoablation, as shown in Figure 2.

[0069] Figure 3 shows a cryobiopss tissue sampling device 100 according to a conceptual embodiment of the present invention. In this embodiment, the device 100 includes an outer sheath for introducing a cryoprobe 10 into the body and ultimately into the lumen of the heart. The cryoprobe 10 includes an elongated catheter having a proximal end and a distal end. The distal end comprises a probe tip 26, and the proximal end comprises a refrigerant inlet port 18 and a refrigerant outlet port 19. A liquid refrigerant 27 is introduced into the probe 10 through the inlet port 18. The liquid refrigerant is injected into the probe tip 26 through at least one microtube inside the probe 10, the probe tip defining a cavity, inside the cavity, where the liquid refrigerant evaporates and transitions from a liquid state to a gaseous state, thereby lowering the temperature of the probe tip 26. The refrigerant, as a gas, is exhausted from the probe tip to the outlet port 19 through a path inside the probe 10. The outlet port may be a vacuum port configured to connect to a vacuum to facilitate the exhaust of the refrigerant gas from the probe tip. The pressure of the liquid refrigerant decreases as it leaves the microtube and enters the probe tip. This pressure drop within the probe tip causes a change of state from liquid to gas.

[0070] In some embodiments, the cryoprobe 10 includes a flexible 9-French probe 12. The handle 14 includes a lever controller 16 that allows steering of the probe 10 within the body. The lever controller 16 also allows the user to control the curvature of the tip for maneuvering, as seen in arrow 23. The probe 10 includes a liquid coolant input port 18 and a coolant output port 19. The probe 10 may include an electrical connector 22 for driving a ring electrode 25 at the distal end of the probe. The electrical connector 22 can be coupled to a appropriately configured controller 24 that includes cryobiopsis logic for controlling the magnitude and duration of the freezing temperature at the probe tip 26, and for taking tissue by extraction of the probe sheath. The device may include a user interface (UI) 21 that allows the user to interact with the device and the probe 10 via the controller 24.

[0071] Figure 4 is a flowchart of one embodiment of the cardiac cryobioplasty method 400 according to a conceptual aspect of the present invention. The method 400 in Figure 4 can be performed using the apparatus shown in Figure 3, etc. According to some embodiments, the cryoprobe 10 is introduced into the body through a sheath and ultimately into the ventricle (S30). The probe tip 26 is directed to the tissue sampling site (S31). The probe tip 26 can be brought to freezing temperature after or immediately before contact with the tissue (S33).

[0072] The temperature of the probe tip 26 can be controlled according to a sampling temperature profile that determines the magnitude and duration of the temperature required to collect tissue (or cells) at that site. The profile may have a constant probe tip temperature during sampling, or the temperature may change or have different levels during various parts of the process. In some embodiments, the temperature may be controlled by an operator or a pre-programmed controller. Temperature, surface area, pressure of the probe tip against the heart wall, and duration may be parameters used in defining the sampling profile and may be monitored and / or controlled at the probe tip. However, unlike cryoablation, the objective is to collect living cells, not to damage or destroy tissue at the site where ablation is performed.

[0073] The probe tip 26 is maintained at the freezing sampling temperature during sampling, but also at the freezing withdrawal temperature after sampling is completed at the sampling site. Therefore, the cryoprebe can be withdrawn through the sheath without releasing the collected tissue sample by thawing (S34). The sampling temperature and the withdrawal temperature may be the same or different, but are preferably below freezing point in various embodiments.

[0074] In some embodiments, the probe tip 26 may include at least one sensor 30, such as a photodetector, to indicate whether tissue cells have been collected, as shown in Figure 3A. The sensor 30 may be part of a feedback loop with a controller 24 that affects and / or controls the temperature of the probe tip 26. For example, when the sensor indicates that collection is complete, a signal can be sent to the operator and / or the controller 24. The operator and / or the controller 24 can then adjust the probe temperature to the withdrawal temperature if it differs from the collection temperature, and withdraw the probe 10. In various embodiments, if the collected tissue 32 on the probe tip 26 blocks the photodetector 30, for example, if light is reflected inside the probe tip 26, it is determined that a tissue sample is attached to the probe tip for collection.

[0075] After withdrawal from the body, various methods can be used to remove the frozen tissue sample from the probe tip 26. In various embodiments, once the probe 10 is detached from the sheath and body, the temperature of the probe tip 26 rises above freezing point, allowing the collected tissue sample to be released from the probe. In various embodiments, releasing the collected tissue sample from the probe may include removing the tissue sample or cells from the tissue sample from the probe tip 26. In other embodiments, releasing the collected tissue sample from the probe may include removing the probe tip 26 or a portion thereof from the probe 10 with the tissue sample still attached, and the tissue sample 32 can be sent for analysis with the probe tip 26 or a portion thereof, while the sample is still frozen rather than being thawed beforehand.

[0076] In various embodiments, the cardiac cryobioplasty method includes the steps of introducing a cryoprobe into the ventricle of the body (S30), maneuvering the probe tip 26 to the tissue sampling site (S31), raising the probe tip 26 to a sampling temperature below freezing point (S33), maintaining contact until cardiac tissue or cells 32 adhere to the probe tip due to freezing (S34), and withdrawing the probe tip from the body while maintaining the probe tip below freezing point (S35).

[0077] In some embodiments, the method may further include the step of raising the temperature of the probe tip above freezing point after it has been removed from the body to release the collected cardiac tissue or cells.

[0078] In some embodiments, the method may further include the step of removing the probe tip or any part thereof, with the cardiac tissue or cells attached, from the probe after the probe tip has been removed from the body.

[0079] In some embodiments, the cryoprobe 10 includes an elongated catheter having a proximal end and a distal end. The distal end may include a probe tip 26, and the proximal end may include a refrigerant inlet port 18 and a refrigerant outlet port 19. The method may include the steps of introducing a refrigerant through the catheter to the probe tip 26 via the inlet port 18 to lower the temperature of the probe tip, and exhausting the refrigerant through the catheter shaft via the outlet port 19. The refrigerant may be discharged as a refrigerant gas from the outlet port 19.

[0080] In some embodiments, the probe tip 26 includes a microtube 28, and the method 400 includes the steps of: injecting a refrigerant as a liquid refrigerant into the probe tip 26 through the microtube 28; evaporating the refrigerant in the probe tip 26 to lower the temperature of the probe tip; and exhausting the refrigerant as a refrigerant gas from the probe tip 26 and the outlet port 19.

[0081] In some embodiments, the method may further include the step of controlling the temperature of the probe tip 26 by a controller 24 equipped with a processor.

[0082] In some embodiments, the probe tip 26 includes at least one sensor coupled to a processor, and the method further includes the step of sensing the temperature of the probe tip 26 and / or the coolant entering and / or leaving the probe tip 26.

[0083] In some embodiments, the method further includes the step of sensing the presence and / or absence of cardiac tissue or cells attached to the probe tip 26.

[0084] In some embodiments, the method further includes the step of establishing a feedback loop between at least one sensor and a controller 24 so that the controller 24 can monitor and adjust the temperature of the probe tip 26.

[0085] While we have described what we consider to be the best mode and / or other preferred embodiments, please understand that various modifications are possible, and the present invention can be carried out in various forms and embodiments and applied to many uses, but only some of them have been described herein. The appended claims are intended to claim the invention as described and all its equivalents, including all variations and modifications that fall within the scope of each claim.

[0086] For clarity, it should be understood that certain features of the invention described in the context of individual embodiments can also be provided in combination in a single embodiment. Conversely, various features of the invention described in the context of a single embodiment for brevity can also be provided individually or in any suitable partial combination.

[0087] For example, it should be understood that all features described in any of the claims (whether independent or dependent) can be combined in any given way.

Claims

1. A cryoprobe having an ultra-low temperature probe tip and configured to be introduced into the patient's ventricle through the patient's blood vessels, A steering mechanism configured to direct the tip of the probe toward the tissue sampling site within the ventricle, A cardiac cryobiopsy apparatus comprising a controller equipped with a processor, wherein the controller is The tip of the probe is cooled to below freezing point, and cardiac tissue and / or cells are allowed to adhere to the tip of the probe. Maintain the temperature of the probe tip below freezing point while withdrawing the probe tip from the patient's body with the collected cardiac tissue and / or cells attached. A cardiac cryobiopsy device characterized by being configured in such a way.

2. The apparatus according to claim 1, The aforementioned controller further, After the probe tip is removed from the body, the temperature of the probe tip is raised above the freezing point to release the collected cardiac tissue and / or cells from the probe tip. A device characterized by being configured in such a way.

3. The apparatus according to claim 1, characterized in that, after the probe tip is removed from the body, the probe tip or a part thereof can be detached from the probe together with the attached collected cardiac tissue and / or cells.

4. The apparatus according to claim 1, The cryoprobe, A proximal end having an inlet port and an outlet port, A microtube configured to inject the liquid refrigerant received through the inlet port into the probe tip, and It further includes, The probe tip defines a chamber configured to receive the liquid refrigerant and lower the temperature of the probe tip by transitioning the liquid refrigerant from a liquid state to a gaseous state. The probe defines the gas exhaust path from the tip of the probe to the outlet port. A device characterized by the following features.

5. The apparatus according to claim 4, wherein the controller is further configured to control the flow of the refrigerant in the probe and thereby control the temperature at the tip of the probe.

6. The apparatus according to claim 5, characterized in that the probe tip includes at least one sensor which is coupled to the processor and configured to sense at least one state at the probe tip.

7. The apparatus according to claim 6, characterized in that the at least one state includes a temperature state and / or the presence of the collected cardiac tissue and / or cells attached to the tip of the probe.

8. The apparatus according to claim 6, characterized in that the controller and the at least one sensor are configured to sense the temperature of the probe tip and / or the temperature of the refrigerant entering and / or leaving the probe tip.

9. The apparatus according to claim 6, characterized in that the controller and the at least one sensor are configured to sense the presence and / or absence of cardiac tissue or cells attached to the tip of the probe.

10. The apparatus according to claim 6, characterized in that the at least one sensor includes at least one optical sensor configured to sense the presence and / or absence of the collected cardiac tissue and / or cells attached to the tip of the probe.

11. The apparatus according to claim 6, further comprising a feedback loop between the at least one sensor and the controller, wherein the controller can monitor and adjust the probe tip temperature.

12. The apparatus according to claim 6, characterized in that the controller is configured to maintain the temperature of the probe tip below freezing point for at least 10 seconds, at least 30 seconds, or at least 1 minute after it leaves the body.

13. The apparatus according to claim 6, characterized in that the controller is configured to maintain the probe tip temperature below freezing point after it has left the body, until a user input received via the user interface instructs the controller to raise the probe tip temperature above freezing point.

14. The apparatus according to claim 13, wherein the controller is further configured to include an ambient temperature sensor, and to set the probe tip temperature inside the ventricle based on the ambient temperature sensed outside the body.

15. The apparatus according to claim 14, wherein the controller is further configured to set the duration for which the probe tip should be below freezing point outside the body, based on the ambient temperature.

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