Detachable CRYO-probe tip and probe system comprising same

Abstract

Provided is a cryo-probe, comprising a catheter, a detachable cryo-probe tip; and a cryogenic source configured to selectively bring the cryo-probe tip to at least a freezing temperature or below and back above freezing temperature. The cryo-probe tip can be a cryobiopsy probe tip. A magazine may be provided to store the detached cryobiopsy probe tips.

Description

DETACHABLE CRYO-PROBE TIP AND PROBE SYSTEM COMPRISING SAMECROSS-REFERENCES TO RELATED APPLICATIONS

[0001] The present application claims priority under 35 USC 119 from U.S. Provisional Application No. 63 / 546,575 filed October 31, 2023, the contents of which are incorporated by reference in its entirety.FIELD OF INTEREST

[0002] The present inventive concepts relate to the field of medicine and, in particular, to methods and apparatuses for biopsying tissue.BACKGROUND

[0003] Endomyocardial biopsy delivers small tissue samples for examination in a pathology lab from the inner lining of the heart, known as the endocardium. Endomyocardial biopsy is a valuable diagnostic tool and, in particular, is a technique used on a patient over a sizable duration of time to monitor rejection in transplant patients, with many regular repeat procedures.

[0004] Traditionally a specialized catheter with biopsy forceps, a bioptome, is inserted through a large vein, see FIGS. 1A-D. The catheter is carefully guided into the right atrium and ventricle of the heart, and then small tissue samples are obtained from the endocardium using the biopsy instrument, here forceps. Catheter control and sampling consistency are both challenging, requiring skill and dexterity, but with substantial subjectivity contributing to a significant complication rate and a wariness amongst practitioners.

[0005] Typically, several biopsies are taken at each procedure (e.g., 5) and although it is an accepted technique, it can cause trauma and long-term scaring at the sample site, which is due to the limited navigability (tool steering and imaging) that then tends to track to relatively localized areas of the endocardium that may be very patient specific. Another drawback of this approach is that the utility of samples taken using a bioptome are limited by size and crush artifacts caused by the forceps.

[0006] Meanwhile, cryoablation is an accepted technique in cardiology, used as one possible treatment for cardiac arrhythmia. This is a completely different procedure than endomyocardial biopsy. Cryoablation is a therapeutic process and does not sample and removetissue whereas endomyocardial biopsy is a diagnostic process and not a treatment for any cardiac condition. Cryoablation platforms are well established in cardiology departments in the United States and Europe, and the majority of these systems use the Joule Thomson effect to provide cooling at the catheter tip. Cryoablation systems are available from large and established medical technology (“medtech”) companies, including Boston Scientific, Medtronic, Atricure, and Erbe.

[0007] Cryobiopsy, i.e., tissue sampling using a cryo-probe, has been used in the lung in bronchoscopy and has been shown to offer advantages over mechanical sampling. (See Cryobiopsy in Lung Cancer Diagnosis — A Literature Review . Marioara Simon, Ioan Simon, Paul Andrei Tent, Doina Adina Todea and Antonia Harangus. Medicina (Kaunas).2021 Apr; 57(4): 393. But the problem of sampling cardiac tissue using cryobiopsy has not been addressed with no known attempts to solve and no solution proposed.

[0008] It would be beneficial to provide cryobiopsy of heart tissue as an alternative to the use of a bioptome, preferably with cryobiopsy providing a better tissue sampling approach with less damage to the sampled tissue, a procedure that can be delivered reliably repetitively and with reduced risks to patients. It would be further beneficial to apply the same or similar cryobiopsy approaches to other tissue.SUMMARY

[0009] In accordance with aspects of the inventive concepts, provided is a cryo-probe, comprising: a catheter; a detachable cryo-probe tip; and a cryogenic source configured to selectively bring the cryo-probe tip to at least a freezing temperature or below and back above freezing temperature.

[0010] In various embodiments, the probe tip forms a detachable magnetic connection with the probe.

[0011] In various embodiments, the probe tip forms a detachable electromagnetic connection with the probe.

[0012] In various embodiments, the probe tip forms a detachable press fit or compression fit connection with the probe.

[0013] In various embodiments, the probe tip forms a detachable threaded connection with the probe.

[0014] In various embodiments, the cryo-probe tip is a cryobiopsy probe tip.

[0015] In various embodiments, the cryogenic source is further configured to transition the cryo-probe tip to a temperature above freezing.

[0016] In various embodiments, cryo-probe further comprises a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

[0017] In various embodiments, the tissue sampling site is internal to the body.

[0018] In various embodiments, the tissue sampling site is within a body cavity.

[0019] In various embodiments, the tissue sampling site is within an organ.

[0020] In various embodiments, the tissue sampling site is within an endocardium.

[0021] In accordance with another aspect of the inventive concepts, provide is a cryo- probe tip that is detachable from a cryo-probe or catheter.

[0022] In various embodiments, the probe tip forms a detachable magnetic connection with the probe.

[0023] In various embodiments, the probe tip forms a detachable electromagnetic connection with the probe.

[0024] In various embodiments, the probe tip forms a detachable press fit or compression fit connection with the probe.

[0025] In various embodiments, the probe tip forms a detachable threaded connection with the probe.

[0026] In various embodiments, the cryo-probe tip is a cryobiopsy probe tip.

[0027] In accordance with another aspect of the inventive concepts, provided is a cryobiopsy apparatus, comprising a shaft; a detachable cryo-probe tip removably coupled to the shaft; and a cryogenic source configured to bring the cryo-probe tip to at least a freezing temperature or below.

[0028] In various embodiments, the cryo-probe tip is configured to sample tissue at a tissue sampling site external to the body, optionally, including a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

[0029] In various embodiments, the apparatus further comprises a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

[0030] In various embodiments, the tissue sampling site is internal to the body.

[0031] In various embodiments, the tissue sampling site is within a body cavity.

[0032] In various embodiments, the tissue sampling site is within an organ.

[0033] In various embodiments, the tissue sampling site is within an endocardium.

[0034] In various embodiments, the probe tip forms a detachable magnetic connection with the probe.

[0035] In various embodiments, the probe tip forms a detachable electromagnetic connection with the probe.

[0036] In various embodiments, the probe tip forms a detachable press fit or compression fit connection with the probe.

[0037] In various embodiments, the probe tip forms a detachable threaded connection with the probe.

[0038] In various embodiments, the cryo-probe tip is a cryobiopsy probe tip.

[0039] In various embodiments, the cryogenic source is further configured to transition the cryo-probe tip to a temperature above freezing.

[0040] In accordance with another aspect of the inventive concepts, provided is a cryobiopsy method, comprising providing a cryobiopsy delivery device comprising, which includes a detachable cryo-probe tip coupled to a shaft and a cryogenic source. The method includes delivering the cryo-probe tip to a tissue sampling site; bringing the cryo-probe tip to at least a freezing temperature or below; withdrawing the probe tip from the site; and detaching the probe tip from the shaft.

[0041] In various embodiments, the tissue sampling site is external to the body and, optionally, includes a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

[0042] In various embodiments, the method further comprises steering the shaft and probe tip to a tissue sampling site with a steering mechanism.

[0043] In various embodiments, the tissue sampling site is internal to the body.

[0044] In various embodiments, the tissue sampling site is within a body cavity.

[0045] In various embodiments, the tissue sampling site is within an organ.

[0046] In various embodiments, the tissue sampling site is within an endocardium.

[0047] In various embodiments, the probe tip forms a detachable magnetic connection with the probe.

[0048] In various embodiments, the probe tip forms a detachable electromagnetic connection with the probe.

[0049] In various embodiments, the probe tip forms a detachable press fit or compression fit connection with the probe.

[0050] In various embodiments, the probe tip forms a detachable threaded connection with the probe.

[0051] In various embodiments, the cryo-probe tip is a cryobiopsy probe tip.

[0052] In various embodiments, the method further comprising the cryogenic source transitioning the cryo-probe tip to a temperature above freezing.

[0053] In accordance with another aspect of the inventive concept, provided is a cryobiopsy kit, comprising a shaft; at least one detachable cryo-probe tip configured to removably couple to the shaft; and a cryogenic source configured to bring the cryo-probe tip to at least a freezing temperature or below.

[0054] In accordance with another aspect of the inventive concepts, provided is a cryobiopsy probe kit, comprising a shaft and at least one detachable cryo-probe tip configured to removably couple to a shaft. In various kit embodiments, further comprises a cryogenic source configured to transition the at least one cryo-probe tip to a temperature above freezing.

[0055] In various kit embodiments, the cryo-probe tip is configured to sample tissue at a tissue sampling site external to the body, optionally, including a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

[0056] In various kit embodiments, either of the above kits further comprises a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

[0057] In various kit embodiments, the tissue sampling site is internal to the body.

[0058] In various kit embodiments, tissue sampling site is within a body cavity.

[0059] In various kit embodiments, the tissue sampling site is within an organ.

[0060] In various kit embodiments, the tissue sampling site is within an endocardium.

[0061] In various kit embodiments, the probe tip forms a detachable magnetic connection with the probe.

[0062] In various kit embodiments, the probe tip forms a detachable electromagnetic connection with the probe.

[0063] In various kit embodiments, the probe tip forms a detachable press fit or compression fit connection with the probe.

[0064] In various kit embodiments, the probe tip forms a detachable threaded connection with the probe.

[0065] In various kit embodiments, the at least one cryo-probe tip is or includes a cryobiopsy probe tip.BRIEF DESCRIPTION OF THE DRAWINGS

[0066] The present invention will become more apparent in view of the attached drawings and accompanying detailed description. The embodiments depicted therein are provided by way of example, not by way of limitation, wherein like reference numerals refer to the same or similar elements. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating aspects of the invention. In the drawings:

[0067] FIGS. 1A-1C show an embodiment of a prior art bioptome used for endomyocardial biopsy.

[0068] FIG. ID shows prior art forceps of the bioptome shown in FIGS. 1A-1C.

[0069] FIG. 2 is an example embodiment of cryobiopsy system using a heart as an example of a tissue sampling site, in accordance with aspects of the inventive concepts.

[0070] FIG. 3 is an example embodiment of a cryo-delivery catheter, in accordance with aspects of the inventive concepts.

[0071] FIGS. 4A through 4C show an embodiment of a cryobiopsy tissue sample being harvested using a cryobiopsy probe (or “cryo-probe”), in accordance with aspects of the inventive concepts.

[0072] FIG. 5 part (A) shows a cryobiopsy tissue sample and FIG. 5 part (B) shows tissue sampling using a cryo-probe, in accordance with aspects of the inventive concepts.

[0073] FIG. 6 shows an embodiment of a detachable cryo-probe tip, in accordance with aspects of the inventive concepts.

[0074] FIG. 7 shows another embodiment of a detachable cryo-probe tip, in accordance with aspects of the inventive concepts.

[0075] FIG. 8 shows yet another embodiment of a detachable cryo-probe tip, in accordance with aspects of the inventive concepts.

[0076] FIG. 9 shows another embodiment of a cryobiopsy probe with a detachable cryo-probe tip, in accordance with aspects of the inventive concepts.

[0077] FIG. 10 shows another embodiment of a cryobiopsy probe with a detachable cryo-probe tip, in accordance with aspects of the inventive concepts.

[0078] FIG. 11 shows an embodiment of a detachable cryo-probe tip storage device, in accordance with aspects of the inventive concepts.DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0079] Various aspects of the inventive concepts will be described more fully hereinafter with reference to the accompanying drawings, in which some exemplary embodiments are shown. The present inventive concept may, however, be embodied in many different forms and should not be construed as limited to the exemplary embodiments set forth herein.

[0080] It will be understood that, although the terms first, second, etc. are be used herein to describe various elements, these elements should not be limited by these terms. These terms are used to distinguish one element from another, but not to imply a required sequence of elements. For example, a first element can be termed a second element, and, similarly, a second element can be termed a first element, without departing from the scope of the present invention. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0081] It will be understood that when an element is referred to as being “on” or “connected” or “coupled” to another element, it can be directly on or connected or coupled to the other element or intervening elements can be present. In contrast, when an element is referred to as being “directly on” or “directly connected” or “directly coupled” to another element, there are no intervening elements present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” etc.).

[0082] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a,” "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises," "comprising," "includes" and / or "including," when used herein, specify the presence of stated features, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0083] To the extent that functional features, operations, and / or steps are described herein, or otherwise understood to be included within various embodiments of the inventive concept, such functional features, operations, and / or steps can be embodied in functional blocks, units, modules, operations and / or methods. And to the extent that such functional blocks, units, modules, operations and / or methods include computer program code, suchcomputer program code can be stored in a computer readable medium, e.g., such as non- transitory memory and media, that is executable by at least one computer processor.

[0084] Provided is a catheter and a process for performing an endomyocardial biopsy for cardiac diagnosis which differs from the standard approach. In various embodiments, the process uses a catheter with a cryo tip to ‘freeze capture’ the biopsy sample, rather than mechanically cutting away the tissue sample with a bioptome (See FIGS. 1A-1D).

[0085] The approach proposed is cryobiopsy sampling, using a catheter comprising a probe that can freeze a local tissue sample around its probe tip and withdraw the attached tissue on extraction, still attached to the probe tip. In preferred embodiments, the cryo-probe tip is detachable so that it can be separated from the cryo-probe when removed from the body, with the tissue still attached to the tip. The use of cryobiopsy in accordance with the inventive concepts will enable better histological, molecular and genetic analysis of frozen tissue samples.

[0086] In accordance with aspects of the inventive concepts, provided is a system and method used to perform a cryobiopsy procedure with a steerable cryo-probe having a detachable probe tip. This approach to endomyocardial biopsy provides an efficient means of taking a number of sequential biopsies, e.g., where a subsequent sample can be taken by attaching a new cryo-probe tip, reinserting the probe, and repeating the endomyocardial biopsy procedure.

[0087] In accordance with the inventive concepts, the cryobiopsy catheter includes a removable and replaceable tip attached to a steerable cryo-catheter or cryo-probe, enabling sequential samples to be collected using the same “single procedure” catheter with different cryo-probe tips. The set of collected samples can then be passed to a pathology laboratory for analysis or even analyzed in the surgical suite or cardiology facility / cardiac catheter laboratory close to the patient and the geographical location of sampling.

[0088] In various embodiments, the cryobiopsy probe includes a removable tip, Joule Thomson biopsy catheter.

[0089] Four concept options or embodiments for a cryobiopsy catheter in accordance with the inventive concepts are summarized below:

[0090] 1. Joule Thomson cooled catheter: a bespoke designed catheter with a removable tip using Joule Thomson cooling. In various embodiments, the complex console and catheter design can leverage the approach used by ‘on-market’ cardiac cryoablation systems adapted for cryobiopsy. For usability, in some embodiments, a “magazine” ofpotentially bar-coded replaceable tips can be provided where a ‘sample transfer device’ would provide storage of the tips, fitment of the tips, and could be used for transfer of biopsy samples to the pathology laboratory.

[0091] 2. Cryogenic liquid recirculation cooled catheter: a bespoke designed catheter using an alternative cooling technology is the approach used by CPSI Biotech. Various embodiments could utilize a miniaturized console: potentially a desk top device or even more appealing, part of the catheter handpiece and possibly disposable . This approach would remove a bulky console from the hospital and reduce the complexity of the console - complexity that leads to greater effort during product development and a greater burden for maintaining the product. The tip magazine concept would be maintained and appropriately modified from option 1 above.

[0092] CPSI Biotech provides platforms based on pressurized subcooled nitrogen (PSN) and supercritical nitrogen (CSN). CPSI Biotech does not currently appear to make an FDA cleared cryo-console, but in various embodiments such platforms could be adapted for use in accordance with aspects of the inventive concepts.

[0093] 3. Endothermic reaction tip: as another embodiment of the fully disposable product concept, it could be feasible to use an approach such as endothermic reaction chilling of a replaceable tip. This “self-chilling” tip would be fitted to a custom steerable catheter, with less design complexity than a Joule-Thomson catheter and would deliver a triggerable onetime chilling event to the biopsy site. No console would then be required. There are many fundamental challenges to this approach, but we note CPSI Biotech presents CryoPellets™ - using self-contained cryogen pellets (seeds) that are injected into a target tissue to generate a lesion. This suggests that they may have solved many of the challenges of size, triggering and energy absorption which can be adapted for the intended application. In various embodiments, therefore, CryoPellets could be used to cool the cryo tips, in accordance with the inventive concepts.

[0094] 4. Tips for use with existing ablation catheters: perhaps the simplest embodiment of a biopsy kit is to develop a tip design for use with cryoablation hardware already in service in cardiology. Potentially a range of tips and magazines could be designed to interact with unmodified third party cryoablation catheters and consoles, broadening accessibility beyond one provider’s system. The technical challenge would be attachment to an unmodified catheter not designed specifically for this purpose.

[0095] Ex vivo cryobiopsy experiments provide very useful data for selection of the optimal cryo-technology and system concept. The recipes (or profdes) of cooling temperatures and cooling times will be a key requirement for the system. The cooling times used for cryobiopsy in bronchoscopy are notably shorter than the cooling time used in cryoablation for cardiac arrythmia. Cooling times of 5-10secs are typically reported and vary with the diameter of cryo-catheter used.

[0096] FIG. 2 is an example embodiment of cryobiopsy system 100, in accordance with aspects of the inventive concepts. In FIG. 2, a heart H of a patient P is shown, and the cryobiopsy system 100 includes a console 200, a cryobiopsy catheter 300. The cryobiopsy catheter 300 includes a cryogenic probe (or “cryo-probe”) having a cryo-probe tip 326 at a distal end of a catheter shaft 310. Cryo-probe tip 326 is preferably a detachable probe tip in accordance with aspects of the inventive concepts.

[0097] The console 200 can include at least one display 210 and a processing unit 230 comprising one or more processors, memory, and power sources. The memory can store program logic executable by the one or more processors to perform one or more steps of a cryobiopsy method. The processing unit 230 can include a thermal controller 240, which can include at least one of the one or more processors, configured to control a probe tip temperature. For example, the thermal controller 240 of the console 200 can be configured to control the flow of a refrigerant, such as liquid nitrogen, to the probe tip, thereby controlling the probe tip temperature at the distal end of the cryobiopsy catheter 300. In other embodiments, other forms of temperature control can be provided for the tip.

[0098] The console display 210 can be configured to display information, instructions, graphs, charts, anatomy, data streams, and / or real-time monitored parameters related to the patient P, the heart H, the cryo- biopsy catheter 300, and / or its probe tip, and / or a procedure being performed. The console 200 can also include one or more user-interactive mechanisms 214, e.g., knobs, dials, switches, keys, keyboard, camera, and / or sensors, useful and / or necessary for controlling the console display and / or the cryo- biopsy catheter 300, including the thermal controller 240. In some embodiments, the console display 210 can be a touch- sensitive display configured to receive user inputs useful and / or necessary for controlling the console display 210 and / or the cryobiopsy catheter 300. In some embodiments, the console display 210 could take the form of or include a mobile device and / or wireless device, such as a laptop, desktop computer, tablet, mobile phone, and / or smart television, as examples, and theone or more user interactive mechanism 214 could be user interactive mechanisms of such mobile and / or wireless device.

[0099] The cryo- biopsy catheter 300 having a thermally controllable distal end including a removable cryo-probe tip 326 can be delivered through a sheath 110 to the target site, where the tissue to be sampled or treated is located. The cryobiopsy catheter 300 can include one or more connectors 320 in the form of wires, cables, tubes, and / or conduits, such as for the exchange of electrical signals, control signals, sensor signals, refrigerant delivery, and / or refrigerant related venting or evacuation. Connectors 320 can couple to the cryogenic console 200 via at least one port 216.

[0100] FIG. 3 is an example embodiment of the cryobiopsy catheter 300, in accordance with aspects of the inventive concepts. In this embodiment, the cryobiopsy catheter 300 includes at least one elongate, flexible catheter shaft 310 that can be introduced, via sheath 110, into the body of a patient P and, ultimately, into an inner chamber of the heart H. In other embodiments, other organs or tissue could be sampled or treated by the cryobiopsy catheter 300, e.g., lungs, liver, stomach, etc.

[0101] The cryobiopsy catheter 300 has a proximal end and a distal end. The distal end, which is also the distal end of the catheter shaft 310, comprises a removable cryobiopsy probe tip 326, in accordance with aspects of the inventive concepts. The proximal end of the cryobiopsy catheter 300 comprises a refrigerant inlet port 318 and a refrigerant outlet port 319. Liquid refrigerant 327 is introduced into the cryobiopsy catheter 300 via the inlet port 318. The liquid refrigerant 327 is injected into the probe tip 326 via at least one micro-tube 328 within the shaft 310 of the cryobiopsy catheter 300. In some embodiments, the catheter shaft 310 comprises a Flexible 9 French tube.

[0102] In this embodiment, the cryobiopsy probe tip 326 is configured to be controllably cooled, wherein the liquid refrigerant evaporates to transition the refrigerant from a liquid state to a gas state, thereby controllably lowering the temperature of the cryobiopsy probe tip 326. The thermal controller 240 can regulate the flow of the refrigerant to regulate the temperature of the probe tip. The refrigerant, as gas, is evacuated via a path within the cryobiopsy catheter 300 from the probe tip to the outlet port 319. The outlet port 319 can be a vacuum port configured to connect to a vacuum that aids in the evacuation of the refrigerant gas from the cryobiopsy probe tip 326. The pressure of liquid refrigerant drops as it leaves the microtubes 328 and is delivered proximate the cryobiopsy probe tip 326. The decrease inpressure of the refrigerant causes the state change to from a liquid to a gas, thereby controlling the temperature of the cryobiopsy probe tip.

[0103] At the proximal end of the catheter shaft 310 is a handle 314 that includes lever controls 316 that enable steering of the catheter shaft 310 and probe tip 326 inside the body. The lever controls 316 also enable a user to control and manipulate tip curvature, as seen by arrows 323. The proximal end includes the liquid refrigerant input port 318 and the refrigerant output port 319. The cryobiopsy catheter 300 can include an electrical connector 322 for driving ring electrodes 325 at the distal end and probe tip 326. The electrical connector 322 could be coupled to a properly configured thermal controller 240 that includes cryobiopsy logic for controlling a magnitude and a duration of freezing temperatures at the cryo-probe tip 326. The cryo-probe tip 326 can be removable once withdrawn from the body and deposited into a container or magazine for subsequent testing.

[0104] FIGS. 4A through 4C show an embodiment of a cryobiopsy tissue sample being harvested using a cryobiopsy catheter and probe tip in accordance with aspects of the inventive concepts. For example, the tissue can be the endocardium, in some embodiments. In other embodiments, the cryobiopsy catheter with detachable cryobiopsy probe tip can be used to sample tissue from other organs and / or parts of the body.

[0105] In FIG. 4A, a cryobiopsy probe having a removable cryo-probe tip 426 is shown, where the cryobiopsy probe tip 426 has been brought into contact with the tissue 428. After such contact, the probe tip 426 is cooled below freezing, which then freezes a region of the tissue 432.

[0106] In FIG. 4B, the withdrawal of the probe has begun and at least a portion of the frozen tissue 430 is adhered by freezing to the cryobiopsy probe tip 426, which leaves a small wound 434 in the tissue. Frozen tissue 430 is the harvested tissue that can be later used for testing. The removal of the tip from the surface in early iterations is planned to be via simple traction but mechanical engineering approaches could lead to devices that will facilitate removal from surfaces by mechanisms not requiring applied traction and therefore be automatic.

[0107] In FIG. 4C, the cryobiopsy probe, including probe tip, has been withdrawn from the body and the tissue 430 remains frozen to the probe tip 426. The probe tip 426 can then be removed and stored for subsequent testing of the tissue.

[0108] FIG. 5 part (A) shows a cryobiopsy tissue sample 530, in accordance with aspects of the inventive concepts. And FIG. 5 part (B) shows tissue sampling using a cryo-probe having a probe tip 526 sampling tissue from a tissue site 528, in accordance with aspects of the inventive concepts. The sample 530 in (A) is taken from the right ventricle with the cryo-probe tip at -40 degrees Celsius for 10 seconds. The sample in (A) is shown removed from the cryo-probe tip. The sample in (B) is being taken from the bronchus with the cryo- probe tip 526 at site 528 at -40 degrees Celsius for 10 seconds. In this figure, the probe tip 526 is shown in contact with the bronchus tissue.

[0109] In accordance with aspects of the inventive concepts, all manner of descriptions of detachable cryo-probe tips can be provided, e.g., clip on, screw-on, slide-on, and of various materials e.g., glass, metal, plastics, ceramics etc.

[0110] FIG. 6 shows an embodiment of a detachable cryo-probe tip, in accordance with aspects of the inventive concepts. In FIG. 6, a detachable cryo-probe tip 626 is detachable from a cryo- probe or catheter 610. The probe tip 626 can have an opening that forms a press fit or friction fit with the catheter 610, as an example.

[0111] FIG. 7 shows another embodiment of a detachable cryo-probe tip, in accordance with aspects of the inventive concepts. In FIG. 7, a detachable cryo-probe tip 726 is detachable from a cryo- probe or catheter 710. The probe tip 726 can have an opening that forms a magnetic or electromagnetic fit with the catheter 710, as an example. In this embodiment, the probe tip 726 or the catheter 710 can include a magnetic or electromagnetic material 712 and the catheter or probe tip can be formed of or include a magnetic material. If the magnet is an electromagnet, then a current can be run through the catheter while in the body and then the current can be terminated when the probe tip is outside the body to release the probe tip.

[0112] FIG. 8 shows yet another embodiment of a detachable cryo-probe tip, in accordance with aspects of the inventive concepts. In FIG. 8, a detachable cryo-probe tip 826 is detachable from a cryo- probe or catheter 810. The probe tip 826 and the probe 810 can be threaded so they can screw together. In this example, the probe has an externally threaded portion 812 and the probe tip has an internally threaded portion. Other configurations can be employed in other embodiments.

[0113] While the cryobiopsy processes, systems, apparatuses, and probe tips described herein are generally described with respect to internal tissue sampling, in various embodiments the foregoing may be applied to external tissue sampling, such as sampling skin, dermal layer sampling, and / or subcutaneous sampling. Cryotherapy has been used on the skin, but cryobiopsy for diagnostic purposes would also be advantageous. Furthermore, whether internal or external, cryobiopsy with a removal probe tip would be particularly advantageous.

[0114] FIG. 9 shows another embodiment of a cryobiopsy apparatus with a detachable cryo-probe tip, in accordance with aspects of the inventive concepts. In this embodiment, the cryobiopsy apparatus 900 can be used for performing cryobiopsies outside the body or external to the body. Such cryobiopsies could be performed at a tissue sample site 928 on the skin or dermal layer of the skin 930, and / or subcutaneously. If subcutaneously, the probe tip 926 could include or be paired with a cutting or piercing device configured to cut into the skin 930 to take a cryobiopsy of the tissue to be sampled 932 below the surface of the skin (e.g., see piercing device 1027 of FIG. 10).

[0115] In this example, the cryobiopsy apparatus 900 includes a shaft in the form of a handle 910, at least one detachable cryo-probe tip 926 configured to removably couple to the shaft, and a cryogenic source 200 configured to bring the cryo-probe tip to at least a freezing temperature or below. The handle 910 can include a mechanism, switch, or button 912 configured to control the cryogenic source 200 to lower the temperature of the cryo-probe tip 926. The probe tip 926 can be removably attached to the handle 910, e.g., by any detachable mechanism described herein or otherwise apparent to those skilled in the art having the benefit of this disclosure. In some embodiments, a release 913 can be included on the handle to release the probe tip 926 from the body 910.

[0116] Once the cryo-probe tip 926 is brought to a freezing temperature or below it can be brought into contact with the tissue 928 (at the tissue sampling site) and once the tissue is adhered by freezing to the probe tip 926, the probe tip can be withdrawn from the tissue sampling site with tissue adhered thereto for subsequent testing and / or evaluation. In other embodiments, the probe tip 926 can be brought into contact with the tissue to be sampled 928, then brought to a temperature at or below freezing, and then withdrawn.

[0117] FIG. 10 shows another embodiment of a cryobiopsy apparatus with a detachable cryo-probe tip, in accordance with aspects of the inventive concepts. In this embodiment, the cryobiopsy apparatus 1000 can be used for performing cryobiopsies outside the body or external to the body. Such cryobiopsies could be performed at a tissue sample site 1028 on the skin or dermal layer of the skin 1030, and / or subcutaneously. If subcutaneously, the probe tip 1026 could optionally include or be paired with a cutting or piercing device 1027 configured to cut into the skin 1030 to take a cryobiopsy of the tissue to be sampled 1032 below the surface of the skin.

[0118] In this example, the cryobiopsy apparatus 1000 includes a shaft 1010, at least one detachable cryo-probe tip 1026 configured to removably couple to the shaft, and acryogenic source 200 configured to bring the cryo-probe tip to at least a freezing temperature or below. In this embodiment, the apparatus 1000 includes a body 1006 that forms a lumen through which the shaft 1010 and the cryo-probe tip 1026 can travel. In this embodiment, the shaft 1010 includes a plunger 1002, where a spring 1004 (or other compressible member) can be disposed between the plunger 1002 and the body 1006 to bias the shaft so that the probe tip 1026 is maintained within the body 1006 unless and until the plunger 1002 is depressed. The plunger can be depressed to bring the probe tip 1026 into contact with the tissue to be sampled 1032.

[0119] In some embodiments, once the cryo-probe tip 1026 is brought to a freezing temperature or below it can be brought into contact with the tissue 1028 (at the tissue sampling site) and once the tissue is adhered by freezing to the probe tip 1026. In other embodiments, the probe tip 1026 can be brought into contact with the tissue to be sampled, then brought to a temperature at or below freezing, and then withdrawn. In either case, the probe tip can be withdrawn from the tissue sampling site with tissue adhered thereto for subsequent testing and / or evaluation.

[0120] FIG. 11 shows an embodiment of a detachable cryo-probe tip storage device, in accordance with aspects of the inventive concepts. In various embodiments, the storage device is a magazine 1100 that can hold a plurality of detached probe tips. In this example, the magazine includes a body 1110 and a cover 1112 that can close the body to secure and maintain any probe tips stored therein. In various embodiments, once closed, the magazine is preferably airtight and waterproof. In various embodiments, once closed, the magazine is also thermally insulating.

[0121] In FIG. 11, the probe tip 826 includes a material 830 attached by freezing thereto. The probe tip 826 can be stored in an individual compartment 1120 of the magazine.

[0122] In various embodiments, the cryobiopsy device is removed from the body with the tip attached and the sample frozen firmly. The detached cryobiopsy probe tip can then be detached and placed in a receptacle, which could be bar coded and not frozen but chilled. The device, or probe tip magazine, could look something like those holding pipette tips in labs e.g., see an embodiment of a cryobiopsy probe tip holder 600 in FIG. 6. This probe tip holder can hold 6 probe tips, in separate compartments 602, but other probe tips holders can be provided that provide less or more probe tip holder compartments. In some embodiments, a single probe tip holder could be provided that holds a single probe tip. While the foregoing has described what are considered to be the best mode and / or other preferred embodiments, it is understoodthat various modifications can be made therein and that the invention or inventions may be implemented in various forms and embodiments, and that they may be applied in numerous applications, only some of which have been described herein. It is intended by the following claims to claim that which is literally described and all equivalents thereto, including all modifications and variations that fall within the scope of each claim.

[0123] Although much of the foregoing refers to accessing the heart via the blood vessels (vasculature) to apply the cryobiopsy probe for sampling other organs and tissues can also be sampled applying the same principles and toolkit. As examples, the vasculature can be used to apply the cryobiopsy tissue sampling procedures described to e.g., the liver, kidneys etc., indeed any tissue receiving a blood vessel supply.

[0124] In various embodiments, the described cryobiopsy probe can also be used for sampling via any other hollow organs so access tissues applying the same principles and toolkit. These organs and organ systems may be located in the head and neck e.g., ears, nasopharynx, oral cavities, the esophagus, stomach, upper intestine, biliary tract and liver, lower intestines, rectum, urogenital tracts, uterus, cervix and ovaries, as examples.

[0125] Cryobiopsy is already applied to the lung, but cryobiopsy tool and toolkits in accordance with the inventive concepts provide unique, differentiated capabilities in the bronchi, bronchial tree and lungs in general being steerable, but more specifically through the provision of detachable tips that offer particular advantages for taking samples for molecular and genetic indications.

[0126] In addition to access to the vasculature and to ‘hollow organs,’ the same cryobiopsy approach is applicable to cavity spaces accessible using conventional approaches. Accordingly, ‘keyhole’, ‘minimally invasive’ access to the abdomen and thorax can be anticipated. In the abdomen our steerable cryobiopsy probe would be applicable to sampling from the liver, the kidneys, the gastrointestinal tract in general, the appendix, the ovaries, the uterus, the bladder, the adrenals, the lymph nodes, the spleen and the inner linings of the abdominal wall. Similarly within the thorax the same cryobiopsy procedures are applicable to sampling from the pleura, lungs, esophagus, mediastinum, lymph nodes, heart epicardium and inner walls of the thorax. The steerable design, but more specifically the provision of detachable tips will offer particular advantages for taking samples for molecular and genetic indications.

[0127] While the inventive concepts have been described with respect to tissue biopsy, they could also be applied in other contexts involving alteration and / or removal of tissue. Suchother forms of tissue could include, but need not be limited to, cauterization and / or resection of tissue. In various embodiments, cauterization, or cautery, could be used to alter and / or remove tissue in order to close a wound. It may also be done to remove harmful tissue. Resection is a medical term for surgically removing part or all of a tissue, structure, or organ. Resection may be performed for a variety of reasons, including to remove tissue that is known to be cancerous or diseased or to treat or cure a disease process. In such cases, cryobiopsy consistent principles description herein can be applied to such procedures.

[0128] Below follows an itemized list of statements describing embodiments in accordance with the inventive concepts:

[0129] 1. A cryo-probe, comprising: a catheter; a detachable cryo-probe tip; and a cryogenic source configured to selectively bring the cryo-probe tip to at least a freezing temperature or below and back above freezing temperature.

[0130] 2. The cryo-probe of statement 1 , or any other statement or combination of statements, wherein the probe tip forms a detachable magnetic connection with the probe.

[0131] 3. The cryo-probe of statement 1 , or any other statement or combination of statements, wherein the probe tip forms a detachable electromagnetic connection with the probe.

[0132] 4. The cryo-probe of statement 1, or any other statement or combination of statements, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

[0133] 5. The cryo-probe of statement 1, or any other statement or combination of statements, wherein the probe tip forms a detachable threaded connection with the probe.

[0134] 6. The cryo-probe of statement 1, or any other statement or combination of statements, wherein the cryo-probe tip is a cryobiopsy probe tip.

[0135] 7. The cryo-probe of statement 1, or any other statement or combination of statements, wherein the cryogenic source is further configured to transition the cryo-probe tip to a temperature above freezing.

[0136] 8. The cryo-probe of statement 1 , or any other statement or combination of statements, further comprising a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

[0137] 9. The cryo-probe of statement 8, or any other statement or combination of statements, wherein the tissue sampling site is internal to the body.

[0138] 10. The cryo-probe of statement 9, or any other statement or combination of statements, wherein the tissue sampling site is within a body cavity.

[0139] 11. The cryo-probe of statement 9, or any other statement or combination of statements, wherein the tissue sampling site is within an organ.

[0140] 12. The cryo-probe of statement 9, or any other statement or combination of statements, wherein the tissue sampling site is within an endocardium.

[0141] 13. A cryo-probe tip that is detachable from a cryo- probe or catheter.

[0142] 14. The cryo-probe tip of statement 13, or any other statement or combination of statements, wherein the probe tip forms a detachable magnetic connection with the probe.

[0143] 15. The cryo-probe tip of statement 13, or any other statement or combination of statements, wherein the probe tip forms a detachable electromagnetic connection with the probe.

[0144] 16. The cryo-probe tip of statement 13, or any other statement or combination of statements, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

[0145] 17. The cryo-probe tip of statement 13, or any other statement or combination of statements, wherein the probe tip forms a detachable threaded connection with the probe.

[0146] 18. The cryo-probe tip of statement 13, or any other statement or combination of statements, wherein the cryo-probe tip is a cryobiopsy probe tip.

[0147] 19. A cryobiopsy apparatus, comprising: a shaft; a detachable cryo-probe tip removably coupled to the shaft; and a cryogenic source configured to bring the cryo-probe tip to at least a freezing temperature or below.

[0148] 20. The apparatus of statement 19, or any other statement or combination of statements, wherein the cryo-probe tip is configured to sample tissue at a tissue sampling site external to the body, optionally, including a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

[0149] 21. The apparatus of statement 19, or any other statement or combination of statements, further comprising a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

[0150] 22. The apparatus of statement 21 , or any other statement or combination of statements, wherein the tissue sampling site is internal to the body.

[0151] 23. The apparatus of statement 22, or any other statement or combination of statements, wherein the tissue sampling site is within a body cavity.

[0152] 24. The apparatus of statement 22, or any other statement or combination of statements, wherein the tissue sampling site is within an organ.

[0153] 25. The apparatus of statement 22, or any other statement or combination of statements, wherein the tissue sampling site is within an endocardium.

[0154] 26. The apparatus of statement 19, or any other statement or combination of statements, wherein the probe tip forms a detachable magnetic connection with the probe.

[0155] 27. The apparatus of statement 19, or any other statement or combination of statements, wherein the probe tip forms a detachable electromagnetic connection with the probe.

[0156] 28. The apparatus of statement 19 or any other statements or combination of statements, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

[0157] 29. The apparatus of statement 19, or any other statement or combination of statements, wherein the probe tip forms a detachable threaded connection with the probe.

[0158] 30. The apparatus of statement 19, or any other statement or combination of statements, wherein the cryo-probe tip is a cryobiopsy probe tip.

[0159] 31. The apparatus of statement 19, or any other statement or combination of statements, wherein the cryogenic source is further configured to transition the cryo-probe tip to a temperature above freezing.

[0160] 32. A cryobiopsy method, comprising: providing a cryobiopsy delivery device comprising: a detachable cryo-probe tip coupled to a shaft; and a cryogenic source; delivering the cryo-probe tip to a tissue sampling site; bringing the cryo-probe tip to at least a freezing temperature or below; withdrawing the probe tip from the site; anddetaching the probe tip from the shaft.

[0161] 33. The method of statement 32, or any other statement or combination of statements, wherein the tissue sampling site is external to the body and, optionally, includes a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

[0162] 34. The method of statement 32, or any other statement or combination of statements, further comprising steering the shaft and probe tip to a tissue sampling site with a steering mechanism.

[0163] 35. The method of statement 34, or any other statement or combination of statements, wherein the tissue sampling site is internal to the body.

[0164] 36. The method of statement 35, or any other statement or combination of statements, wherein the tissue sampling site is within a body cavity.

[0165] 37. The method of statement 35, or any other statement or combination of statements, wherein the tissue sampling site is within an organ.

[0166] 38. The method of statement 35, or any other statement or combination of statements, wherein the tissue sampling site is within an endocardium.

[0167] 39. The method of statement 32, or any other statement or combination of statements, wherein the probe tip forms a detachable magnetic connection with the probe.

[0168] 40. The method of statement 32, or any other statement or combination of statements, wherein the probe tip forms a detachable electromagnetic connection with the probe.

[0169] 41. The method of statement 32, or any other statement or combination of statements, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

[0170] 42. The method of statement 32, or any other statement or combination of statements, wherein the probe tip forms a detachable threaded connection with the probe.

[0171] 43. The method of statement 32, or any other statement or combination of statements, wherein the cryo-probe tip is a cryobiopsy probe tip.

[0172] 44. The method of statement 32, or any other statements or combination of statements, further comprising the cryogenic source transitioning the cryo-probe tip to a temperature above freezing.

[0173] 45. A cryobiopsy kit, comprising: a shaft; at least one detachable cryo-probe tip configured to removably couple to the shaft; anda cryogenic source configured to bring the cryo-probe tip to at least a freezing temperature or below.

[0174] 46. A cryobiopsy probe kit, comprising: a shaft; and at least one detachable cryo-probe tip configured to removably couple to a shaft.

[0175] 47. The kit of statement 45 or 46, or any other statements or combination of statements, wherein the cryo-probe tip is configured to sample tissue at a tissue sampling site external to the body, optionally, including a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

[0176] 48. The kit of statement 45 or 46, or any other statement or combination of statements, further comprising a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

[0177] 49. The kit of statement 48, or any other statement or combination of statements, wherein the tissue sampling site is internal to the body.

[0178] 50. The kit of statement 48, or any other statement or combination of statements, wherein the tissue sampling site is within a body cavity.

[0179] 51. The kit of statement 48, or any other statement or combination of statements, wherein the tissue sampling site is within an organ.

[0180] 52. The kit of statement 48, or any other statement or combination of statements, wherein the tissue sampling site is within an endocardium.

[0181] 53. The kit of statement 45 or 46, or any other statement or combination of statements, or any other statement or combination of statements, wherein the probe tip forms a detachable magnetic connection with the probe.

[0182] 54. The kit of statement 45 or 46, or any other statement or combination of statements, wherein the probe tip forms a detachable electromagnetic connection with the probe.

[0183] 55. The kit of statement 45 or 46, or any other statement or combination of statements, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

[0184] 56. The kit of statement 45 or 46, or any other statement or combination of statements, wherein the probe tip forms a detachable threaded connection with the probe.

[0185] 57. The kit of statement 45 or 46, or any other statement or combination of statements, wherein the at least one cryo-probe tip is or includes a cryobiopsy probe tip.

[0186] 58. The kit of statement 46, or any other statement or combination of statements, further comprising a cryogenic source configured to transition the at least one cryoprobe tip to a temperature above freezing.

[0187] 59. The kit of statement 46, or any other statement or combination of statements, wherein the kit is configured for cauterization and / or resection of tissue.

[0188] 60. The cryo-probe of statement 1 , or any other statement or combination of statements, wherein the cryo-probe is configured for cauterization and / or resection of tissue.

[0189] 61. The cryo-probe tip of statement 13, or any other statement or combination of statements, wherein the cryo-probe tip is configured for cauterization and / or resection of tissue.

[0190] 62. The apparatus of statement 19, or any other statement or combination of statements, wherein the apparatus is configured for cauterization and / or resection of tissue.

[0191] 63. The method of statement 32, or any other statement or combination of statements, wherein the method includes performing for cauterization and / or resection of tissue.

[0192] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment may also be provided separately or in any suitable sub-combination.

[0193] For example, it will be appreciated that all of the features set out in any of the claims (whether independent or dependent) can combined in any given way.

Claims

What is claimed is:

1. A cryo-probe, comprising: a catheter; a detachable cryo-probe tip; and a cryogenic source configured to selectively bring the cryo-probe tip to at least a freezing temperature or below and back above freezing temperature.

2. The cryo-probe of claim 1, wherein the probe tip forms a detachable magnetic connection with the probe.

3. The cryo-probe of claim 1, wherein the probe tip forms a detachable electromagnetic connection with the probe.

4. The cryo-probe of claim 1, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

5. The cryo-probe of claim 1, wherein the probe tip forms a detachable threaded connection with the probe.

6. The cryo-probe of claim 1, wherein the cryo-probe tip is a cryobiopsy probe tip.

7. The cryo-probe of claim 1, wherein the cryogenic source is further configured to transition the cryo-probe tip to a temperature above freezing.

8. The cryo-probe of claim 1, further comprising: a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

9. The cryo-probe of claim 8, wherein the tissue sampling site is internal to the body.

10. The cryo-probe of claim 9, wherein the tissue sampling site is within a body cavity.

11. The cryo-probe of claim 9, wherein the tissue sampling site is within an organ.

12. The cryo-probe of claim 9, wherein the tissue sampling site is within an endocardium.

13. A cryo-probe tip that is detachable from a cryo- probe or catheter.

14. The cryo-probe tip of claim 13, wherein the probe tip forms a detachable magnetic connection with the probe.

15. The cryo-probe tip of claim 13, wherein the probe tip forms a detachable electromagnetic connection with the probe.

16. The cryo-probe tip of claim 13, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

17. The cryo-probe tip of claim 13, wherein the probe tip forms a detachable threaded connection with the probe.

18. The cryo-probe tip of claim 13, wherein the cryo-probe tip is a cryobiopsy probe tip.

19. A cryobiopsy apparatus, comprising: a shaft; a detachable cryo-probe tip removably coupled to the shaft; and a cryogenic source configured to bring the cryo-probe tip to at least a freezing temperature or below.

20. The apparatus of claim 19, wherein the cryo-probe tip is configured to sample tissue at a tissue sampling site external to the body, optionally, including a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

21. The apparatus of claim 19, further comprising: a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

22. The apparatus of claim 21, wherein the tissue sampling site is internal to the body.

23. The apparatus of claim 22, wherein the tissue sampling site is within a body cavity.

24. The apparatus of claim 22, wherein the tissue sampling site is within an organ.

25. The apparatus of claim 22, wherein the tissue sampling site is within an endocardium.

26. The apparatus of claim 19, wherein the probe tip forms a detachable magnetic connection with the probe.

27. The apparatus of claim 19, wherein the probe tip forms a detachable electromagnetic connection with the probe.

28. The apparatus of claim 19, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

29. The apparatus of claim 19, wherein the probe tip forms a detachable threaded connection with the probe.

30. The apparatus of claim 19, wherein the cryo-probe tip is a cryobiopsy probe tip.

31. The apparatus of claim 19, wherein the cryogenic source is further configured to transition the cryo-probe tip to a temperature above freezing.

32. A cryobiopsy method, comprising: providing a cryobiopsy delivery device comprising: a detachable cryo-probe tip coupled to a shaft; and a cryogenic source; delivering the cryo-probe tip to a tissue sampling site; bringing the cryo-probe tip to at least a freezing temperature or below;withdrawing the probe tip from the site; and detaching the probe tip from the shaft.

33. The method of claim 32, wherein the tissue sampling site is external to the body and, optionally, includes a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

34. The method of claim 32, further comprising: steering the shaft and probe tip to a tissue sampling site with a steering mechanism.

35. The method of claim 34, wherein the tissue sampling site is internal to the body.

36. The method of claim 35, wherein the tissue sampling site is within a body cavity.

37. The method of claim 35, wherein the tissue sampling site is within an organ.

38. The method of claim 35, wherein the tissue sampling site is within an endocardium.

39. The method of claim 32, wherein the probe tip forms a detachable magnetic connection with the probe.

40. The method of claim 32, wherein the probe tip forms a detachable electromagnetic connection with the probe.

41. The method of claim 32, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

42. The method of claim 32, wherein the probe tip forms a detachable threaded connection with the probe.

43. The method of claim 32, wherein the cryo-probe tip is a cryobiopsy probe tip.

44. The method of claim 32, further comprising:the cryogenic source transitioning the cryo-probe tip to a temperature above freezing.

45. A cryobiopsy kit, comprising: a shaft; at least one detachable cryo-probe tip configured to removably couple to the shaft; and a cryogenic source configured to bring the cryo-probe tip to at least a freezing temperature or below.

46. A cryobiopsy probe kit, comprising: a shaft; and at least one detachable cryo-probe tip configured to removably couple to a shaft.

47. The kit of claim 45 or 46, wherein the cryo-probe tip is configured to sample tissue at a tissue sampling site external to the body, optionally, including a portion of skin, a portion of a dermal layer, and / or subcutaneous tissue.

48. The kit of claim 45 or 46, further comprising: a steering mechanism configured to steer the shaft and probe tip to a tissue sampling site.

49. The kit of claim 48, wherein the tissue sampling site is internal to the body.

50. The kit of claim 48, wherein the tissue sampling site is within a body cavity.

51. The kit of claim 48, wherein the tissue sampling site is within an organ.

52. The kit of claim 48, wherein the tissue sampling site is within an endocardium.

53. The kit of claim 45 or 46, or any other claim or combination of claims, wherein the probe tip forms a detachable magnetic connection with the probe.

54. The kit of claim 45 or 46, wherein the probe tip forms a detachable electromagnetic connection with the probe.

55. The kit of claim 45 or 46, wherein the probe tip forms a detachable press fit or compression fit connection with the probe.

56. The kit of claim 45 or 46, wherein the probe tip forms a detachable threaded connection with the probe.

57. The kit of claim 45 or 46, wherein the at least one cryo-probe tip is or includes a cryobiopsy probe tip.

58. The kit of claim 46, further comprising: a cryogenic source configured to transition the at least one cryo-probe tip to a temperature above freezing.

59. The kit of claim 46, wherein the kit is configured for cauterization and / or resection of tissue.

60. The cryo-probe of claim 1, wherein the cryo-probe is configured for cauterization and / or resection of tissue.

61. The cryo-probe tip of claim 13, wherein the cryo-probe tip is configured for cauterization and / or resection of tissue.

62. The apparatus of claim 19, wherein the apparatus is configured for cauterization and / or resection of tissue.

63. The method of claim 32, wherein the method includes performing cauterization and / or resection of tissue.

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