Systems, devices and methods relating to manufacture of prosthetic valves

Abstract

To provide systems, devices and methods relating to the manufacture of prosthetic valves.SOLUTION: Improved prosthetic heart valves and methods of manufacturing the same are described. An environmental humidity chamber can be used in methods of valve leaflet manufacture for a first phase of curing. In some instances, methods of manufacturing a polymeric valve prosthesis can include applying an identifier 700 to the prothesis 102. The identifier 700 can be covered by a polymer but remain readable through the polymer.SELECTED DRAWING: Figure 10A

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 547,034, filed August 17, 2017, and U.S. Provisional Patent Application No. 62 / 541,575, filed August 4, 2017, both of which are incorporated by reference in their entirety and for all purposes.

[0002] The subject matter described herein relates generally to improved replacement valves, and more particularly to improved techniques for the manufacture and manufacturability of prosthetic valves, such as prosthetic heart valves having artificial polymer leaflets. [Background technology]

[0003] The human heart has several valves to maintain the proper direction of blood flow through the body. The main valves of the heart are the atrioventricular (AV) valves, including the bicuspid (mitral) and tricuspid valves, and the semilunar valves, including the aortic and pulmonary valves. When healthy, each of these valves operates in a similar manner. The valves transition between an open state (allowing blood flow) and a closed state (preventing blood flow) in response to pressure differences across the valve.

[0004] A patient's health can be at serious risk if any of these valves begin to malfunction. Malfunctioning can be due to a variety of reasons, but typically results in either stenosis or regurgitation, which restricts blood flow, allowing blood to flow in the wrong direction. If the defect is severe, the heart valve may require replacement surgery.

[0005] Enormous efforts have been expended in developing replacement heart valves, most notably replacement aortic and mitral valves. Replacement valves can be implanted percutaneously, using a catheter introduced transfemorally or transapically, or directly through open heart surgery. Replacement valves typically include an array of leaflets that are machined from porcine tissue. These tissue leaflets are highly expandable or extensible, and the manufacture of the valve involves manual suturing of the leaflets to a support.

[0006] Other replacement valves have artificial polymeric leaflets that are integrally formed with a supporting structure. Although these artificial leaflet valves have demonstrated promise, the techniques for manufacturing such artificial leaflets and valves are in their early stages and are not suitable for larger scale manufacturing.

[0007] For these and other reasons, a need exists for improved systems, devices, and methods for manufacturing prosthetic valves with artificial leaflets. Summary of the Invention [Means for solving the problem]

[0008] Provided herein are several exemplary embodiments of systems, devices, and methods for manufacturing or for use in manufacturing a prosthetic heart valve. Many of these embodiments may utilize an environmental humidity chamber (EHC) during the partial curing phase of the liquid polymer, which will form the leaflets on the valve frame after further processing. The EHC can be part of a multi-stage manufacturing process, and in some embodiments, the multi-stages include applying the liquid polymer to the valve frame and leaflet-forming structure, then partially curing the liquid polymer in the EHC, and then removing the valve frame and leaflet-forming structure and exposing the partially cured polymer to another curing stage. Variations and additional steps of this process can be implemented as well.

[0009] Also provided herein are several exemplary embodiments of systems, devices, and methods for utilizing an identifier applied to a valve frame during the manufacturing process. The identifier can represent information about the valve or valve frame and can be read using one of several different energy spectra. In some embodiments, the identifier is an optically readable barcode or QR code. In some embodiments, the identifier includes a serial number or other unique identifier of the valve frame, the type of valve or valve frame, and / or the size of the valve or valve frame. The identifier can be applied to the valve frame prior to application of one or more coatings and can remain readable through the coatings. The identifier can be used to maintain traceability of the valve throughout and after the manufacturing process. The identifier can be used to select the appropriate software to manufacture the valve at various stages of the manufacturing process.

[0010] Other systems, devices, methods, features, and advantages of the subject matter described herein will be, or will become, apparent to one of ordinary skill in the art upon review of the following figures and detailed description. All such additional systems, methods, features, and advantages are intended to be included within this description, be within the scope of the subject matter described herein, and be protected by the accompanying claims. Features of the example embodiments are not to be construed in any way as limiting the appended claims unless there is an express recitation of those features in the claims. The present invention provides, for example, the following: (Item 1) 1. A method of manufacturing a valve leaflet, comprising: applying a polymer in a liquid state to a valve frame and a leaflet forming structure; loading the valve frame and the leaflet forming structure into a chamber along with the polymer in a liquid state; automatically moving the valve frame and the leaflet forming structure around the chamber for a period of time during which the polymer at least partially cures. A method comprising: (Item 2) Applying a polymer in a liquid state to the valve frame and the leaflet forming structure comprises: dip-coating the valve frame by immersing at least a portion of the valve frame and the leaflet forming structure in a reservoir filled with a polymer in the liquid state; removing the valve frame and at least a portion of the leaflet forming structure from the reservoir; The method according to item 1, comprising: (Item 3) automatically moving the valve frame and the leaflet forming structure about the chamber for the period of time during which the polymer is at least partially cured, automatically rotating the valve frame and the leaflet forming structure about the chamber in a plane perpendicular to the axis. The method according to item 1, comprising: (Item 4) 4. The method of claim 3, wherein the valve frame and the leaflet forming structure are rotated at least one revolution about the axis. (Item 5) 2. The method of claim 1, wherein the chamber is an environmental humidity chamber (EHC). (Item 6) opening a door to the chamber prior to loading the valve frame and the leaflet plasty structure; closing a door to the chamber after loading the valve frame and the leaflet plasty structure; The method of claim 1, further comprising: (Item 7) 2. The method of claim 1, wherein automatically moving the valve frame and the leaflet forming structure around the chamber comprises moving the valve frame and the leaflet forming structure through at least 50% of a cross-sectional area of ​​the chamber. (Item 8) 2. The method of claim 1, wherein gas is not fanned within the chamber during the period of time. (Item 9) 2. The method of claim 1, further comprising removing the valve frame and the leaflet forming structure from the chamber. (Item 10) 2. The method of claim 1, further comprising cutting excess at least partially cured polymer from the valve frame. (Item 11) 2. The method of claim 1, wherein when the chamber is closed and the valve frame is automatically moved around the chamber, the humidity in the chamber is controlled to ±1%. (Item 12) 2. The method of claim 1, wherein the chamber has a volume of 1,000 cubic inches or less. (Item 13) Item 10. The method of item 1, wherein the valve frame has an optical identifier thereon. (Item 14) The chamber is a first chamber, and the method further comprises: removing the valve frame and the leaflet forming structure from the first chamber after the time period, wherein the polymer is only partially cured; and inserting the valve frame and the leaflet forming structure into a second chamber; heating the valve frame and the leaflet forming structure in the second chamber until the polymer hardens; The method according to item 1, comprising: (Item 15) 15. The method of claim 14, further comprising slicing the hardened polymer to form a plurality of valve leaflets on the valve frame. (Item 16) Item 15. The method of item 14, wherein the polymer that will form a plurality of valve leaflets on the valve structure after removal from the second chamber is 70 to 200 microns thick. (Item 17) The valve frame is a first valve frame, the leaflet formation structure is a first leaflet formation structure, and the method further comprises: applying the polymer in a liquid state to a second valve frame and a second leaflet forming structure; loading the second valve frame and the second leaflet forming structure into the chamber along with the polymer in the liquid state; automatically moving the first valve frame, the first leaflet forming structure, the second valve frame, and the second leaflet forming structure around the chamber over the period of time during which a polymer on the first valve frame, the first leaflet forming structure, the second valve frame, and the second leaflet forming structure is at least partially cured. The method according to item 1, comprising: (Item 18) removing the second valve frame and the second leaflet forming structure from the first chamber after the time period, wherein the polymer is only partially cured; and inserting the second valve frame and the second leaflet forming structure into the second chamber; heating the second valve frame and the second leaflet forming structure in the second chamber until the polymer cures; cutting the hardened polymer to form a plurality of valve leaflets on the second valve frame; 18. The method of claim 17, further comprising: (Item 19) 20. The method of claim 18, wherein the thickness variation between each of the plurality of leaflets on the first valve frame and each of the plurality of leaflets on the second valve frame is less than 10 microns in thickness. (Item 20) 1. A method of manufacturing a valve leaflet, comprising: applying a polymer in a liquid state to a valve frame and a leaflet forming structure; loading the valve frame and the leaflet forming structure into a first chamber along with a polymer in a liquid state and partially curing the polymer while the valve frame and the leaflet forming structure are in the first chamber; loading the valve frame and the leaflet forming structure with a polymer in the partially cured state into a second chamber and curing the polymer while the valve frame and the leaflet forming structure are in the second chamber; A method comprising: (Item 21) Applying a polymer in a liquid state to the valve frame and the leaflet forming structure comprises: dip-coating the valve frame by immersing at least a portion of the valve frame and the leaflet forming structure in a reservoir filled with a polymer in the liquid state; removing the valve frame and at least a portion of the leaflet forming structure from the reservoir; 21. The method according to item 20, comprising: (Item 22) 21. The method of claim 20, further comprising automatically moving the valve frame and the leaflet forming structure around the first chamber for a period of time during which the polymer partially cures. (Item 23) 23. The method of claim 22, wherein automatically moving the valve frame and the leaflet forming structure around the first chamber comprises moving the valve frame and the leaflet forming structure through at least 50% of a cross-sectional area of ​​the chamber. (Item 24) 21. The method of claim 20, further comprising automatically rotating the valve frame and the leaflet forming structure about the first chamber in a plane perpendicular to an axis for a period of time during which the polymer partially cures. (Item 25) 25. The method of claim 24, wherein the valve frame and the leaflet forming structure are rotated at least one revolution about the axis. (Item 26) 25. The method of claim 24, wherein automatically rotating the valve frame and the leaflet forming structure around the first chamber comprises moving the valve frame and the leaflet forming structure through at least 50% of a cross-sectional area of ​​the chamber. (Item 27) 21. The method of claim 20, wherein the first chamber is an environmental humidity chamber (EHC). (Item 28) 21. The method of claim 20, wherein gas is not fanned in the first chamber for a period of time during which the polymer is partially cured. (Item 29) 21. The method of claim 20, further comprising removing the valve frame and the leaflet forming structure from the chamber. (Item 30) 21. The method of claim 20, further comprising cutting excess partially cured polymer from the valve frame prior to loading the valve frame and the leaflet forming structure into the second chamber. (Item 31) 21. The method of claim 20, wherein the humidity in the first chamber and when the polymer is partially cured is controlled to ±1%. (Item 32) 21. The method of claim 20, wherein the first chamber has a volume of 1,000 cubic inches or less. (Item 33) 21. The method of claim 20, wherein the valve frame has an optical identifier thereon. (Item 34) 21. The method of claim 20, further comprising slicing the hardened polymer to form a plurality of valve leaflets on the valve frame. (Item 35) The valve frame is a first valve frame, the leaflet formation structure is a first leaflet formation structure, and the method further comprises: applying a polymer in a liquid state to a second valve frame and a second leaflet forming structure; loading the second valve frame and the second leaflet forming structure into the first chamber along with a polymer in the liquid state and partially curing the polymer while the first valve frame, the first leaflet forming structure, the second valve frame, and the second leaflet forming structure are within the first chamber; loading the second valve frame and the second leaflet forming structure with a polymer in the partially cured state into a second chamber, and curing the polymer while the first valve frame, the first leaflet forming structure, the second valve frame, and the second leaflet forming structure are in the second chamber; 21. The method according to item 20, comprising: (Item 36) Item 36. The method of item 35, further comprising slicing the hardened polymer to form a plurality of valve leaflets on the second valve frame. (Item 37) Item 37. The method of item 36, wherein the thickness variation between each of the plurality of leaflets on the first valve frame and each of the plurality of leaflets on the second valve frame is less than 10 microns in thickness. (Item 38) 36. The method of claim 35, wherein after removal from the second chamber, the polymer on the leaflet forming structure is 70 to 200 microns thick. (Item 39) 1. An apparatus for partially curing a polymer, comprising: A chamber; a moveable fixture within the chamber, the moveable fixture comprising at least one receptacle; and a motor coupled to the moveable fixture and configured to move the fixture; and a humidity sensor within the chamber; a first controllable output in the chamber, the first controllable output configured to controllably dispense a first medium into the chamber; and a second controllable output in the chamber, the second controllable output configured to dispense a second medium in the chamber, the first medium having a higher relative humidity than the second medium; a control system, said control system communicatively coupled to said humidity sensor and said first and second controllable outputs, said control system programmed to control humidity within said chamber; An apparatus comprising: (Item 40) 40. The device of claim 39, wherein the receptacle is configured to hold a valve frame or leaflet forming structure. (Item 41) 40. The apparatus of claim 39, wherein the movable fixture comprises a plurality of receptacles, each configured to hold a valve frame or a leaflet plasty structure. (Item 42) 40. The apparatus of claim 39, wherein the movable fixture is configured to rotate each receptacle through a plane perpendicular to an axis. (Item 43) 40. The apparatus of claim 39, wherein the moveable fixture is configured to rotate and the motor is a rotary motor. (Item 44) 40. The apparatus of claim 39, wherein the moveable fixture is adapted to move the receptacle through at least 50% of a cross-sectional area of ​​the chamber. (Item 45) 40. The apparatus of claim 39, further comprising a cutting system. (Item 46) Item 46. The apparatus of item 45, wherein the cutting system is configured to cut the partially cured polymer. (Item 47) 40. The apparatus of claim 39, wherein the control system is programmed to control humidity in the chamber to within ±1% of a humidity setting. (Item 48) 40. The apparatus of claim 39, wherein the chamber has a volume of 1,000 cubic inches or less. (Item 49) Item 40. The apparatus of item 39, wherein the chamber comprises a door. (Item 50) 50. The apparatus of claim 49, wherein the door is pneumatically actuable. (Item 51) 1. A method for identifying a prosthetic valve, comprising: marking a valve frame of the prosthetic valve with an identifier; coating the valve frame and identifier with a coating agent; reading the identifier through the coating, the identifier being machine readable; and A method comprising: (Item 52) Reading the identifier comprises: reading, with a scanning device, information encoded within the identifier; automatically communicating said information from said scanning device to a computer system via a communications coupling. 52. The method according to item 51, comprising: (Item 53) 53. The method of claim 52, wherein the scanning device comprises a processing circuit and a non-transitory memory, and wherein a plurality of instructions are stored on the non-transitory memory, the plurality of instructions, when executed by the processing circuit, cause the processing circuit to communicate the information from the scanning device to the computer system. (Item 54) 53. The method of claim 52, further comprising processing, by the computer system, information received from the scanning device and outputting corresponding information to a manufacturing device. (Item 55) 55. The method of claim 54, further comprising automatically selecting, by the manufacturing equipment, software programs, functions, or parameters for performing operations or actions on the prosthetic valve based on the corresponding information. (Item 56) 55. The method of claim 54, wherein the computer system comprises a processing circuit and a non-transitory memory, the non-transitory memory having a plurality of instructions stored thereon that, when executed by the processing circuit, cause the processing circuit to process information received from the scanning device and output corresponding information to the manufacturing device. (Item 57) 55. The method of claim 54, wherein the manufacturing equipment comprises a processing circuit and a non-transient memory, wherein a plurality of instructions are stored on the non-transient memory, the plurality of instructions, when executed by the processing circuit, causing the processing circuit to automatically select a software program for performing a manufacturing operation on the valve based on the corresponding information. (Item 58) 52. The method of claim 51, wherein the identifier is optically readable. (Item 59) 59. The method of claim 58, wherein the identifier is at least one of a one-dimensional code, a two-dimensional code, a three-dimensional code, or a sequence of optically recognizable alphanumeric or symbolic characters. (Item 60) 52. The method of claim 51, wherein the identifier is a QR code. (Item 61) 52. The method of claim 51, wherein the identifier represents information about a valve prosthesis. (Item 62) Item 62. The method of item 61, wherein the information comprises at least one of a valve type, a valve size, or a serial number. (Item 63) Item 62. The method of item 61, wherein the information comprises a valve type, a valve size, and a serial number. (Item 64) 64. The method of claim 62 or 63, wherein the valve type is either an aortic valve or a mitral valve. (Item 65) 64. The method of claim 62 or 63, wherein the valve size is one of 17 mm, 19 mm, 21 mm, 23 mm, 25 mm, 27 mm, or 29 mm. (Item 66) 52. The method of claim 51, further comprising automatically selecting a software program, function, or parameter for an automated operation or action to be performed on the valve prosthesis based on information read from the identifier. (Item 67) 67. The method of claim 66, wherein the software program, function, or parameter is for applying a polymer to the coated valve frame and leaflet formation structure, the polymer being for the formation of a plurality of leaflets. (Item 68) Item 68. The method of item 67, further comprising reading the identifier through the coating and the polymer. (Item 69) Item 67. The method of item 66, wherein the software programs, functions, or parameters are for an automated first phase of curing a polymer on the valve frame and on the leaflet forming structure. (Item 70) Item 67. The method of item 66, wherein the software programs, functions, or parameters are for an automated second phase of curing a polymer on the valve frame and on the leaflet forming structure. (Item 71) Item 67. The method of item 66, wherein the software programs, functions, or parameters are for cutting the hardened polymer to form a plurality of valve leaflets on the valve frame. (Item 72) Item 67. The method of item 66, wherein the software program, function, or parameter is for measuring multiple valve leaflets on the valve frame. (Item 73) 67. The method of claim 66, wherein the software programs, functions, or parameters are for automatically transporting the valve frame between manufacturing stages. (Item 74) Item 67. The method of item 66, wherein the software programs, functions, or parameters are for finalizing the valve frame. (Item 75) 1. A prosthetic valve comprising: a frame having an identifier thereon, the identifier being machine readable; a plurality of polymeric leaflets integrally coupled to the frame by a layer of polymer, the layer of polymer covering the identifier, the identifier remaining machine readable through the layer of polymer; A prosthetic valve comprising: (Item 76) 76. The prosthetic valve of claim 75, wherein the identifier represents at least a unique identifier for the prosthetic valve. (Item 77) Item 76. The prosthetic valve of item 75, wherein the identifier represents at least a serial number of the prosthetic valve. (Item 78) 76. The prosthetic valve of claim 75, wherein the identifier represents at least a unique identifier and a type of the prosthetic valve. (Item 79) 76. The prosthetic valve of claim 75, wherein the identifier represents at least a unique identifier and a size of the prosthetic valve. (Item 80) 76. The prosthetic valve of claim 75, wherein the identifier represents at least a unique identifier, a type of the prosthetic valve, and a size of the prosthetic valve. (Item 81) Item 76. The prosthetic valve of item 75, wherein the identifier is an optically readable identifier. (Item 82) 82. The prosthetic valve of claim 81, wherein the identifier is at least one of a one-dimensional code, a two-dimensional code, a three-dimensional code, or a sequence of optically recognizable alphanumeric or symbolic characters. (Item 83) 82. The prosthetic valve of item 81, wherein the optical identifier is a QR code. (Item 84) Item 76. The prosthetic valve of item 75, wherein the frame and the identifier are covered by a coating and a layer of polymer over the coating, and the identifier remains machine readable through both the coating and the layer of polymer. (Item 85) Item 76. The prosthetic valve of item 75, wherein the identifier is readable using radio frequency (RF) energy. (Item 86) 76. The prosthetic valve of claim 75, wherein the prosthetic valve is a prosthetic heart valve. (Item 87) 87. The prosthetic valve of claim 86, wherein the identifier represents at least a type of the prosthetic heart valve. (Item 88) 88. The prosthetic valve of item 87, wherein the type of prosthetic heart valve is either an aortic valve or a mitral valve. [Brief description of the drawings]

[0011] Details of the subject matter described herein, both with respect to its structure and operation, may become apparent by examination of the accompanying figures, in which like reference numerals refer to like parts. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the subject matter. Moreover, all illustrations are intended to convey concepts, and relative sizes, shapes, and other detailed attributes may be illustrated diagrammatically, rather than literally or precisely.

[0012] [Figure 1] FIG. 1 is a perspective view depicting an exemplary embodiment of a prosthetic valve.

[0013] [Figure 2A] FIG. 2A is a photograph depicting an exemplary embodiment of a valve frame.

[0014] [Figure 2B] FIG. 2B is a photograph depicting an exemplary embodiment of a leaflet forming structure.

[0015] [Figure 3A] 3A-3B are flow diagrams depicting an exemplary embodiment of a manufacturing method. [Figure 3B] 3A-3B are flow diagrams depicting an exemplary embodiment of a manufacturing method.

[0016] [Figure 4] 4A-4B are block diagrams depicting an exemplary embodiment of a manufacturing facility.

[0017] [Figure 5A] 5A-5B are photographs depicting the front of an exemplary embodiment of an EHC. [Figure 5B] 5A-5B are photographs depicting the front of an exemplary embodiment of an EHC.

[0018] [Figure 5C] FIG. 5C is a photograph depicting a side view of an exemplary embodiment of an EHC.

[0019] [Figure 5D] 5D-5E are photographs depicting top-down views of an exemplary embodiment of an EHC. [Figure 5E] 5D-5E are photographs depicting top-down views of an exemplary embodiment of an EHC.

[0020] [Figure 6] 6-7 are photographs depicting an exemplary embodiment of a valve frame within a marking fixture. [Figure 7] 6-7 are photographs depicting an exemplary embodiment of a valve frame within a marking fixture.

[0021] [Figure 8] FIG. 8 is a photograph depicting an exemplary embodiment of a valve frame with an identifier.

[0022] [Figure 9] FIG. 9 is a photograph depicting an exemplary embodiment of a valve frame identifier read by a reader device.

[0023] [Figure 10A]FIG. 10A is a block diagram depicting an exemplary embodiment of a device and system for use in reading an identifier and utilizing the information represented thereby.

[0024] [Figure 10B] FIG. 10B is a flow diagram depicting an exemplary embodiment of a method for using the identifiers in a manufacturing process. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] Before the present subject matter is described in detail, it is to be understood that the present disclosure is not limited to particular embodiments described, which may, of course, vary. Also, the scope of the present disclosure may be limited only by the appended claims, and it is to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[0026] Before the present subject matter is described in detail, it is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. Also, it is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0027] Exemplary embodiments described herein relate to improved techniques for the manufacture and manufacturability of prosthetic valves, such as prosthetic heart valves, having a support structure or frame coupled with two or more artificial polymeric leaflets. FIG. 1 is a perspective view depicting an example of a prosthetic valve 100 having a frame 102 and three leaflets 110-1, 110-2, and 110-3. The valve 100 is configured to allow blood to flow from an upstream end 103 to a downstream end 104. The frame 102 has an annular base portion 105, which may have a planar or flat upstream end (not shown) or a curved or scalloped upstream end as shown here. The frame 102 also includes three extensions 106 that protrude from the annular base portion 105 toward the downstream end 104.

[0028] The downstream edge of the extension 106 has a curved interface 107 where the support structure 102 meets the operable base of the leaflets 110. The leaflets 110 each have a free edge 112, and the leaflets 110 are free to move relative to the support structure 102 between open and closed positions to allow and prevent blood flow through the valve 100, respectively. Each of the leaflets 110 can be discrete from the others (as shown here) or can be part of one unitary (monolithic) leaflet body. The leaflets 110 are integrally formed on the frame 102, such as through a casting (e.g., immersion casting) or molding process.

[0029] The annular base portion 105 also includes flanges 108 and 109 between which a sewing cuff (not shown) may be placed. In other valves 100, only a single flange 108 may be present, or flanges 108 and 109 may be omitted entirely. Examples of valves with sewing cuffs are described in U.S. Pat. No. 6,716,244, U.S. Pat. No. 6,755,857, U.S. Pat. No. 7,641,687, and U.S. Patent Application Publication No. 2003 / 0023302, the disclosures of which are incorporated herein by reference in their entirety for all purposes. Other examples of prosthetic heart valves are described, for example, in International Patent Application Publication No. WO2015 / 171190 and U.S. Patent Application Publication No. 2018 / 0116794A1, the disclosures of which are incorporated herein by reference in their entirety for all purposes.

[0030] The frame 102 can be fabricated from one or more materials (e.g., a core structure of one material with a coating of the same or another material). The material is preferably a polymeric material, such as polyetheretherketone (PEEK), polyurethane, polyetherimide (PEI), such as ULTEM, any of the materials used to form the leaflets 110, and others. The leaflets 110 are also preferably fabricated from a polymeric material, including any biostable polyurethane and polyurethane compositions known in the art (e.g., polysiloxane-containing polyurethanes, etc.). Examples of polyurethane-containing leaflets are described in U.S. Patent No. 6,984,700, U.S. Patent No. 7,262,260, U.S. Patent No. 7,365,134, U.S. Patent Publication No. 2017 / 0119923 ("Polyurethane / urea Compositions"), and Yilgor et al., "Silicone containing copolymers: Synthesis, properties and applications," Prog. Polym. Sci. (2013), all of which are incorporated by reference in their entirety for all purposes. Materials with near ideal isotropic non-creep properties are particularly suitable for use in many embodiments. (Exemplary embodiment of prosthetic valve manufacturing using an environmental humidity chamber)

[0031] Described herein are numerous embodiments of systems, devices, and methods for manufacturing a valve 100 having prosthetic polymer leaflets 110. The valve 100 is manufactured in a manner that integrates the leaflets 110 directly with the frame 102 in a seamless manner, such as by coating the mandrel-holding frame 102 with a polymer in liquid form. Thus, the same step that forms the leaflets also bonds them to the frame 102. Manufacturing embodiments will be described herein in the context of an immersion casting or immersion process used to form the leaflets, however, one skilled in the art will recognize that other forming processes (e.g., molding) can be used as well.

[0032] FIG. 2A is a photograph depicting an example of a frame 102 with a single flange 108 prior to the formation of the leaflets 110. FIG. 2B is a photograph depicting an example of a valve plasty or forming structure, also referred to as a mandrel 202, suitable for use in an immersion casting method. In this example, the mandrel 202 is sized to receive the frame 102 in a central (or frame) portion 206, which has an outer surface that is sized to match the inner surface of the frame 102 and also to allow the formation of the leaflets thereon. The dimensions of the central portion 206 vary depending on the size of the frame 102 and the size (e.g., 17 mm, 19 mm, 21 mm, etc.) and type (e.g., aortic, mitral, or other) of the valve being manufactured. The mandrel 202 has a base portion 204 that can be gripped by manufacturing equipment during the manufacturing process. The base portion 204 can thus have a uniform dimension that is the same regardless of the size of the valve being manufactured. During the immersion process, the mandrel 202 is inverted from the orientation shown in FIG. 2B, and a tip portion 208 of the mandrel 202 (which would therefore be at the bottom) can be present to guide polymer outflow after the frame 102 and mandrel 202 are immersed into a container of liquid polymer.

[0033] FIG. 3A is a flow diagram depicting an exemplary embodiment of a method 300 of manufacturing a prosthetic valve 100. At 302, a support structure or frame 102 can be fabricated from a suitable material, such as those described herein. This can be done, for example, by machining (e.g., 3D printing), molding (e.g., injection molding), or otherwise. The frame 102 can then be optionally coated at 304. The coating step 304 can be advantageous, for example, if the frame 102 is fabricated from a first material (e.g., PEEK) that is different from the polymeric material from which the leaflets are fabricated. In that case, it may be desirable to form the leaflets on the frame 102 only after the frame 102 has been pre-coated with the leaflet polymer to provide better coaptation. The frame can be coated by first dipping the core frame into the leaflet polymer having a first viscosity. This is preferably without the mandrel 202 to avoid the formation of the leaflets. If performed with the mandrel 202, the resulting leaflets are removed. In other embodiments, the frame 102 can be coated in other manners, such as by spraying or brushing the coating material thereon. If the frame 102 undergoes the coating step 304, this is preferably followed by a curing step that allows the coating to dry. The coating forms a base coat upon which the leaflets may be formed.

[0034] The leaflets can then be formed in step 306. As described herein, leaflet formation can occur in multiple ways, and an immersion casting process will be described as an example. The frame 102 can first be placed over the mandrel 202 (if not already therein). The mandrel 202 (with the frame 102 thereon) can then be inserted into a reservoir having the leaflet material in a liquid state (e.g., as a solution including a solvent). The mandrel 202 is preferably immersed such that the solution envelops the tip portion 208 and the middle portion 206 of the mandrel 202, including enveloping the frame 102 on the mandrel. The mandrel 202 can be further infiltrated such that some or all of the base portion 204 is coated as well. This immersion process preferably occurs under relatively high temperatures and humidity. Although the methods disclosed herein are not so limited, in some exemplary embodiments, the relative humidity (RH) can be in the range of 20-80% and the temperature can be in the range of 20-50° C.

[0035] Upon removal from the reservoir, the frame 102 and mandrel 202 (including the leaflet casting surfaces) are coated with a layer of liquid polymer that may drip or flow along portion 208 of the mandrel 202. The dipping step 306 may be performed only once, or may be performed multiple times (e.g., two, three, or as many times as desired) to arrive at a fully formed (but unfinished) valve 100. When multiple dipping steps are performed, the dipping may occur into reservoirs with polymers having the same or different viscosities.

[0036] After immersion is completed, the mandrel 202 and valve 100 undergo a first cure phase in step 308, which can be followed by a second cure phase 310. The first cure phase 308 can be a relatively short cure lasting a few minutes, and the second cure phase 310 can be a relatively long cure lasting a few hours. The first cure phase 308 can be performed in an environmental humidity chamber (EHC), which will be described in more detail herein. The objectives for performing the first cure phase can vary, but often this first phase 308 is performed at process conditions that cause the liquid polymer to reach a sufficient viscosity or dryness level to substantially slow or stop bleeding or dripping, sometimes referred to as the onset of leaflet sticking. The level of bleeding affects the thickness of the resulting leaflet 110 and therefore its performance characteristics, making it desirable to maintain a high degree of control during manufacturing.

[0037] After the first phase 308, the excess glued polymer can be shredded, if desired, and the valve 100 can undergo a second curing phase 310. The second phase 310 can occur in a different chamber, such as an oven, to allow the glued polymer to complete a drying process.

[0038] After the curing step 310, the valve 100 may undergo one or more finishing processes at 312, such as one or more of removal of the mandrel 202, trimming, sewing cuff attachment, inspection, packaging, or the like. For example, the leaflets 110 (and optionally the frame 102) may be trimmed and / or otherwise finished to achieve accurate and precise edges and surface smoothness. This may occur, for example, through laser cutting, ultrasonic trimming, water knives, mechanical clamshell cutters, and the like. In some embodiments, the valve 100 is trimmed while still on the mandrel 202 by cutting through the leaflet polymer and mandrel at the intersection between the central portion 206 and the tip portion 208 of the mandrel 202. A sewing cuff may be coupled to the valve 100 (using any flanges, if present), as desired. The valve 100 may undergo visual inspection and / or measurement. The valve 100 can then be packaged in a desired sterile container.

[0039] 3B is a flow diagram depicting an exemplary embodiment of a method 320 of forming leaflets 110 for prosthetic valve 100. Here, method 320 includes the steps of soaking 306, a first curing phase 308, and a second curing phase 310, substantially as described with respect to the embodiment of FIG. 3A. The remaining steps of method 300 can be included, but are optional to method 320.

[0040] 4A and 4B are block diagrams depicting an exemplary embodiment of a manufacturing facility 400 for valve 100. Facility 400 is preferably configured as a sealable clean environment with an internal environment 410 that is controlled with filtered airflow passages entering facility 400 to limit or prevent particulate contamination. Temperature, humidity, ambient pressure, and ambient gas composition (e.g., oxygen levels, nitrogen levels, etc.) within environment 410 can also be controlled and maintained at desired levels by environmental control equipment 408. A computer system 420 having processing circuitry 422 executing control software stored in non-transitory memory 424 can be communicatively coupled to control equipment 408 and can implement control of equipment 408 and thus environment 410. Processing circuitry 422 can be one or more processors, controllers, programmable logic controllers (PLCs), combinations thereof, and the like.

[0041] The facility 400 may include one or more internal chambers in which certain steps of valve manufacturing may be performed. The size of the facility 400 may vary, and in some embodiments is only 1-3 meters wide by 1-3 meters long. In the embodiment of FIG. 4A, the facility 400 includes a first chamber 401 for performing the soaking step 306, a second chamber 402 for performing the first curing phase step 308, and a third chamber 403 for performing the second curing phase step 310. Other chambers may be included for performing other manufacturing steps as desired.

[0042] Each chamber 401-403 has its own internal environment that can be controlled independently from the environment in the other chambers and in the ambient space 410 of the facility 400. Control of the internal environment of each chamber 401-403 can include control of temperature, humidity, composition of internal gas, ambient gas pressure, and the like. Control of the internal environment of each chamber 401-403 can be performed automatically by software executed by a processing circuit 422 of a master computer system 420 that is communicatively coupled to the environmental control equipment 404-406 of each chamber 401-403, respectively. In the embodiment of FIG. 4B, separate chambers 402 and 403 exist for the curing steps 308 and 310, but the soaking step 306 is performed within the ambient environment 410 of the facility 400. In some embodiments, the soaking can be performed within the EHC 402.

[0043] 4A and 4B, an automated device 430 (e.g., a robotic device) can be included to transport the frame 102 (with or without the leaflets 110) from each location or chamber 401-403 to the next location. The automated device 430 can also be communicatively coupled to and under the control of the computer system 420.

[0044] Referring back to the first curing phase 308 of methods 300 and 320, the second chamber 402 can be configured as an environmental humidity chamber (EHC) 402. Figures 5A-5E are photographs of an exemplary embodiment of an EHC 402. Figure 5A is a front view of the EHC 402, Figure 5B is a front view of the EHC 402 with an exemplary embodiment of a mandrel 202 having a valve 100 thereon, Figure 5C is a side view of the EHC 402 with the mandrel 202 and valve 100, and Figures 5D and 5E are top-down views of the EHC 402 during rotation of the mandrel 202 with the valve 100. In some embodiments, the leaflet polymer is transparent or translucent, so when the frame 102 is immersed, the presence of the leaflets 110 may not be readily visible.

[0045] The EHC 402 is a closable chamber with one or more automatic doors 502 that are controllable for the insertion and removal of the valve 100. Immediately after the soaking step 306, the valve 100 (frame 102 with wet polymer in the form of initial leaflets 110) and mandrel 202 can be inserted through the door 502 into a holder, receptacle, or station 506 in the interior space 503 (the processing space between the walls, floor, and ceiling) of the EHC 402, as shown in FIG. 5B. In some embodiments, the door 502 is a piston-actuated or pneumatic sliding door. The door 502 can transition from closed to open and vice versa relatively quickly, for example, in about 15 seconds or less, which can ensure that the humidity level does not fluctuate significantly when opened to the ambient atmosphere 410 of the facility 400. Additionally, the small volume of the EHC 402 allows for fast recovery of the relative humidity level to the desired set level.

[0046] The EHC 402 may include one or more environmental sensors 504 (FIG. 5C) for measuring temperature, humidity, pressure, or other factors. The EHC 402 may be capable of controlling or maintaining the level of humidity within the interior space 503 with high precision. For example, in an embodiment, the humidity within the EHC 402 may be controlled to remain within about ±1% while the valve 100 is within the EHC 402 in a closed state. The length of exposure of the valve 100 within the space 503 may be timed with high precision. For example, the exposure time may be controlled by the processing circuitry 422.

[0047] Control of both humidity level and exposure time can be important in producing leaflets 110 with the desired thickness. It has been shown that leaflets 110 on the same valve 100 processed in the EHC 402 can have leaflet thicknesses within 10 microns (or less) (e.g., 0-10 microns) of one another (i.e., leaflet-to-leaflet thickness variation on a single valve is less than 10 microns) when measured after final curing (e.g., upon subsequent inspection, after removal from the second chamber 403). This generally pertains to leaflets that are fabricated to have a final thickness in the range of 70-200 microns. In some embodiments, it has been found that precise control of these factors can result in reproducible leaflets with average thicknesses within 2-5 microns of one another. In contrast, prosthetic heart valves made with tissue leaflets often have leaflet-to-leaflet variation of 100 microns.

[0048] In some embodiments, the relative humidity (RH) within EHC 402 can be in the range of about 20% to about 95%, or about 30% to about 90%, more preferably about 50% to about 85%. In some embodiments, the exposure time can be about 2 minutes to 20 minutes, or about 3 minutes to 15 minutes, more preferably about 5 minutes to 10 minutes.

[0049] The EHC 402 can include a movable fixture 508 having one or more (in this example, four) holders 506, each configured to grip and / or hold the mandrel 202 while the valve 100 is installed on the mandrel 202 with the wet polymer. In other embodiments, the holders 506 can hold the valve 100 directly. A motor 512 can move the fixture 508 while the valve 100 is within the holder 506. In FIG. 5D, two of the four holders 506 are empty, one holder 506 is occupied by the mandrel 202, and the other holder 506 is hidden from view. In this embodiment, the fixture 508 includes a plate or shelf coupled to an axle, which is coupled to a motor 512, which is configured to rotate the axle and plate while the mandrel 202 is placed thereon, for example, so that each valve 100 experiences the same average environmental exposure within the EHC 402. The mandrel 202 within the fixture 508 can be moved in a plane perpendicular to the axis of rotation around the EHC 402 (FIG. 5E), during which the polymer deposited on the frame 102 and mandrel 202 partially hardens. As they rotate around a path of, for example, about 6 inches in diameter, they delimit a cylindrical space that occupies about 57% of the cross-sectional area of ​​the EHC 402. In this manner, in some embodiments, at least about 50% of the cross-section can be coated. In some embodiments, between one and four stations 506 can process valves 100 in parallel, while in other embodiments, more than four stations 506 can be used in parallel.

[0050] During rotation, liquid polymer may flow out of the mandrel 202, resulting in long chains of semi-solidified polymer extending from the base of the mandrel 202, sometimes all the way to the floor of the EHC 402. The EHC 402 can be equipped with an automated cutting or knife system 514 (FIG. 5B) that can be used to cut off this excess dripping, either by cutting at the location shown in FIG. 5B, lowering the valve 100 to this location, or raising the cutting system 514 to the end of the tip portion 208 of the mandrel and cutting there. This minimizes further potential dripping or overflow or distortion of the leaflets 110 during the second curing process 310.

[0051] In some embodiments, the duration of rotation can range from about 1 to 30 minutes per cycle, such as 5, 7.5, or 10 minutes per cycle. During this time, each valve 100 can be rotated one or more times around the interior of the EHC 402. In one embodiment, each valve 100 can be rotated about 720 degrees (2 rotations) in about 10 minutes or less. This has been found to result in highly consistent inter- and intra-leaflet thicknesses. For example, in one embodiment, the standard deviation across the three leaflets 110 was in the range of about 0 to 5 microns, while without rotation, one of the leaflets was found to be consistently and systematically thicker than the other two by an average of 30 microns.

[0052] The interior space 503 of the EHC 402 can have a relatively small volume. For example, the interior space 503 of the EHC 402 can be approximately 9×9×7 inches. For reference, some conventional approaches utilize a manufacturing chamber approximately 48×36×36 inches in which multiple steps of valve manufacturing are performed in parallel in the same ambient atmosphere. The interior space 503 of the EHC 402 can have a volume that is 1,000 cubic inches or less in some embodiments. This smaller volume and dedicated EHC 402 can allow for more precise control of relative humidity (RH) levels and greater uniformity of the layer of polymer used to form the valve leaflets 110.

[0053] In some embodiments, the humidity within the EHC 402 can be controlled by a variable mixture of relatively dry and moist media, such as, for example, nitrogen and distilled water. The EHC 402 can include a controllable output 516 for the dry media and a controllable output 518 for the relatively moist media. In some embodiments, the dry media (e.g., nitrogen) can be supplied to the EHC 402 at a level of about 1-15 liters / min, or preferably about 8 liters / min. The source can be pressurized, and while a fan can be used in some cases, the EHC 402 can be configured such that gas is not fanned within the EHC 402 during curing. The source of dry media can be bifurcated and fed to both outputs 516 and 518 (FIG. 5C). The dry media can have a RH of 0-5% and can be fed into the interior space 503 to reduce humidity. A moist media (e.g., a combination of dry media and water) can be fed into the interior space 503 and used to increase humidity. A shield or cover 520 can be placed over the outputs 516 and 518 to prevent dry or wet media from coming into direct contact with the cured polymer. Such an approach can ensure optimal operation and fast recovery of humidity (RH) to a desired set point. The control device 405 can be communicatively coupled to the sensor 504 and can control the outputs 516 and 518 to maintain humidity within about ±1% of a target level. The control device 405 can also control and maintain the temperature within the EHC 402 at a target level.

[0054] To produce a consistent nominal valve 100, some of the optimal parameters for certain embodiments were determined to be 80% RH and 5 minutes exposure time for 17mm and 19mm aortic valves, 80% RH and 7.5 minutes exposure time for 21mm aortic valves, 80% RH and 10 minutes exposure time for 23mm aortic valves, 80% RH and 7.5 minutes exposure time for 25mm aortic valves, and 80% RH and 10 minutes exposure time for 27mm aortic valves. Of course, embodiments of the systems, devices, and methods described herein are not limited to the process parameters described and thus can and will vary depending on implementation details.

[0055] The computer system 420 and / or control equipment 405 can cause the door 502 to open and close. The system 420 and / or equipment 405 can also control the triggering or initiation of a rotation sequence, the speed of rotation and duration of exposure within the EHC 402, control of the environment within the EHC 402 (e.g., operation of humidity control lines 516 and 518), processing of readings from the humidity sensor 504, and operation of the cutting system 514. Once the exposure period is over, the system 420 and / or equipment 405 can cause the door 502 to open and each valve 100 to be removed by the automated transport equipment 430 and then transported to the next stage, e.g., chamber 403, for the second curing phase 310. The automated transport equipment 430 can then transport the valves 100 out of the facility 400 so that finishing and other processes can be performed on each valve 100 and the manufacturing process can be completed. (Exemplary embodiment of prosthetic valve manufacturing with applied identifier)

[0056] In the manufacturing embodiments described herein and other manufacturing methods, an identifier can be applied, placed, or marked on a surface of the frame 102 or valve 100. This identifier can represent information about the frame 102 or valve 100. The identifier can be machine readable and can convey information via optical, infrared, or ultraviolet codes, or by radio frequency (RF) energy (e.g., RFID or near field communication (NFC) tags), or otherwise.

[0057] In many embodiments, the identifier, if applied, can be applied to the surface of the frame 102 prior to application of the leaflet coating (e.g., through dip coating step 306) and leaflet undercoat (e.g., coating step 304). One or more coatings can be relatively thin and / or translucent or transparent to optical light (or other frequencies of energy). The identifier can be read visually, optically, and / or otherwise through the overcoat coating and used to track (e.g., mark its time and location) the frame 102 through each step of the manufacturing process that occurs while the identifier is in place. The identifier can also be read before, during, and / or after each manufacturing step for manufacturing equipment (e.g., automated transport equipment 430, chambers 401-403) to load and execute software instructions specific to the manufacture of each specific valve 100.

[0058] FIG. 6 is a photograph depicting an exemplary embodiment of an unmarked frame 102 (e.g., a blank frame) in a fixture 600 (e.g., an etching jig) used to hold the frame 102 during direct application of an identifier marking to the frame 102. FIG. 7 is a photograph depicting an exemplary embodiment of the frame 102 after it has been marked with an optically scannable identifier 700. Various types of marking devices can be used to mark the frame 102 with the identifier 700 directly in or on the surface of the frame 102. In some embodiments, the marking may be done by etching the surface, by applying heat to change the surface coloration, by applying a dye or ink or other substance visually distinguishable from the surface of the frame 102, or by any other suitable means of marking or combinations thereof.

[0059] In some embodiments, a carrier having identifier 700 thereon, such as a printed flexible patch or plate, can be applied to frame 102. In some embodiments, the carrier can be fastened to valve 100 using adhesives, bonding, mechanical fasteners, or any combination thereof. Identifier 700 that is a substrate that can be fastened to frame 102 is preferred, especially when identifier 700 is in the form of an RFID or NFC tag.

[0060] In the embodiment of FIG. 7, the identifier 700 is in the form of a QR code, which can be seen from its shading, which is darker than the surface of the frame 102 itself. FIG. 8 is a photograph depicting the frame 102 with the identifier 700 in more detail. FIG. 9 is a photograph depicting the process of reading the identifier 700 using a reader device 900, which in this embodiment is a scanner or camera for reading optical codes and / or text. For example, the QR code can be read by a Cognex barcode scanning camera. In some embodiments, once the QR code is scanned, the read information is communicated from the scanner 900 by a communication coupling (which may be wired, more preferably wireless) to the computer system 420 communicatively connected thereto. The information read by the reader device 900 can be processed or decoded by the computer system 420.

[0061] The identifier 700 preferably identifies an individual valve 100 with sufficient specificity to distinguish the individual valve 100 from all other valves being processed by a particular piece of manufacturing equipment during a particular time frame. Such an identifier 700 may be referred to herein as a "valve-specific identifier." For example, in an embodiment, the identifier 700 may be a unique identifier that is not used in conjunction with any other valves being processed by a piece of manufacturing equipment. In some embodiments, the identifier 700 may be recycled as long as it is not reused within a period of time where the identification of two different valves 100 may be confused. In some embodiments, the identifier 700 is or may include a unique serial number for the valve 100.

[0062] In some embodiments, the identifier 700 can also include other information, such as "type" information, which may include an identification of the native valve for which the prosthetic valve 100 serves as a replacement valve (e.g., aortic valve, mitral valve, etc.). In some embodiments, the identifier 700 can include a size of the valve 100 (e.g., 17mm, 19mm, 21mm, 23mm, 25mm, 27mm, etc.). In an embodiment, the identifier 700 includes a valve-specific identifier, type information (e.g., aortic valve, mitral valve, etc.), and size information (e.g., 17mm, 19mm, 21mm, 23mm, 25mm, 27mm, etc.). In an embodiment, the identifier 700 can include other information, such as the type of material used to form the valve, or the type of surgical procedure for which the valve 100 may be used / recommended. In some embodiments, the identifier 700 can omit the unique identifier and include only this "type" information.

[0063] In some embodiments, the identifier 700 will at least uniquely identify the valve 100 at all significant stages of manufacturing that occur after the association of the identifier 700 with the valve 100. Furthermore, in some embodiments, the identifier 700 can be read after manufacturing is completed, i.e., after the valve 100 has been distributed from the manufacturer to a distributor or other party involved in selling the valve 100 to a medical practitioner. Thus, any other third party (e.g., distributor, retailer, shipper, medical practitioner, hospital, government agency, etc.) that has possession of the valve 100 can read and utilize the identifier 700 for tracking, inventory control, analysis of clinical trial results, or any other suitable purpose. The identification of the valve 100 can be tracked to a surgical procedure if read by a medical practitioner or hospital with that capability. Thus, the identification of the valve 100 can be associated with an identifier for a particular patient such that the performance of the valve 100 can be tracked in situ, back to the manufacturing stage. The identity of the valve 100 can be confirmed after its removal from the patient, such as by any party capable of reading the identifier 700 for assessment, or by shipping the valve 100 back to the manufacturer.

[0064] The identifier 700 can be in an optically readable form. In some embodiments, the optical identifier 700 can take a number of different configurations. The identifier 700 can be a one-dimensional (1D) code (e.g., a barcode or dot code, etc.), a two-dimensional (2D) code (e.g., a data matrix code, a rapid response (QR) code, an Aztec code, etc.), a three-dimensional (3D) code (e.g., a colored 2D code, etc.), or any combination thereof. The identifier 700 can alternatively be a sequence or array of recognizable characters, such as alphanumeric characters and / or symbols. The information encoded within the identifier 700 can be recognized by a scanning device 900, which can be in the form of optical character recognition (OCR) or equivalent software or hardware (see, e.g., FIG. 9). The identifier 700 can also include a combination of two or more of the aforementioned media (e.g., a 2D code with OCR text).

[0065] The embodiments of the identifier 700 described herein are not limited to optically readable identifiers, and other types of identifiers can be used. For example, in an embodiment, the identifier 700 may be readable using different frequencies of the electromagnetic spectrum, such as ultraviolet, infrared, radio frequency (e.g., RFID or near field communication (NFC) devices or tags). These other forms or frequencies of identifiers can be used alone or in combination with the optically readable forms described above.

[0066] Although not limited as such, an exemplary embodiment will now be described in which identifier 700 is placed on a surface of frame 102 prior to leaflet formation. In this embodiment, identifier 700 contains information that defines the type of valve 100 (such as aortic or mitral), size (e.g., 17 mm to 27 mm in 2 mm increments for aortic valves and 23 to 31 mm in 2 mm increments for mitral valves), and a valve-specific identifier (e.g., a unique serial number) that can be tracked throughout the manufacturing process.

[0067] 10A is a block diagram depicting an example manufacturing environment 1000 including a reader device 900, a computer system 420, and a manufacturing equipment 1010, each communicatively coupled to the other. The reader device 900 is configured to read the identifier 700 from the valve frame 102 (with or without the valve leaflets). The reader device 900 includes a processing circuit 902 and a non-transitory memory 904 that stores software instructions that, when executed by the processing circuit 902, cause the reader device 900 to read the identifier 700. The software instructions can also cause the processing circuit 902 to transfer information read from the identifier 702 to another system, such as the computer system 420 and / or the manufacturing equipment 1010, where the information can be further utilized in manufacturing.

[0068] The non-transitory memory 424 of the computer system 420 includes software instructions that, when executed by the processing circuitry 422, cause the processing circuitry 422 to read information communicated from the reader device 900. The instructions may further cause the processing circuitry 422 to transfer relevant portions of the information to the manufacturing equipment 1010 for further use in manufacturing. The instructions may also, or alternatively, cause the processing circuitry 422 to select appropriate software programs, functions, or parameters for use in manufacturing the valve 100 and either execute that program, function, or parameter or transfer it to the manufacturing equipment 1010 for execution.

[0069] The manufacturing equipment 1010 can include a processing circuit 1012 and a non-transient memory 1014. The non-transient memory 1014 includes software instructions that, when executed by the processing circuit 1012, cause the processing circuit 1012 to read information communicated from either the reader device 900 or the computer system 420. The instructions can further cause the processing circuit 1012 to select appropriate software programs, functions, or parameters for use in manufacturing the valve 100 and execute the programs, functions, or parameters. The manufacturing equipment 1010 can be, for example, the control equipment 404, 405, 406, and / or 408, and the software programs, functions, or parameters can be for control of the chambers 401, 402, 403, and / or the equipment 400. The manufacturing equipment 1010 can be, for example, an automated transport equipment 430, and the software programs, functions, or parameters can be for control of the equipment 430 in moving the valve 100. The manufacturing equipment 1010 can be, for example, a cutting system 514, and the software programs, functions, or parameters can be for control of the cutting system 514 in the EHC 402. The manufacturing equipment 1010 can be, for example, equipment for use in finishing (e.g., cutting, sewing a cuff, measuring, inspecting, packaging) the valve 100, and the software programs, functions, or parameters can be for control of the finishing equipment.

[0070] 10B is a flow diagram depicting an exemplary embodiment of a method 1050 of utilizing the identifier 700 during one or more manufacturing processes. At 1052, the identifier 700 is applied to the frame 102. At 1054, the identifier 700 can be read or scanned using the reader device 900, and the read information can be automatically communicated by the reader device 900 to the computer system 420. In some cases, the frame 102 can be coated, and the reading of the identifier 700 can occur through the coating. At 1056, the computer system 420 can process the information received from the reader device 900 and output the information to the manufacturing equipment 1010 (e.g., facility 400, chambers 401-403, automated equipment 430, etc.). Then, at 1058, the manufacturing equipment 1010 can select a software program or function (or other parameter) to perform an operation or action on the valve 100 based on the received information. In other embodiments, the computer system 420 can select appropriate software programs, functions, or parameters and output them directly to the manufacturing equipment 1010. For example, the computer system 420 can instruct a particular equipment 1010 to execute a particular program.

[0071] The operations and actions selected in 1058 to be performed on the valve 100 can be steps in manufacturing the manufactured valve 100 (e.g., coating the frame 102 in step 304, the immersion step 306, the first cure phase step 308, the second cure phase step 310, or the finishing steps 312 (e.g., cutting, attaching a sewing cuff, visual inspection, packaging). For example, the equipment associated with the valve immersion 306 can receive the type and size of the valve 100 from the computer system 420 and select a processing software program that will ensure that the valve is immersed to the correct depth, at the correct rate, and remains immersed for the correct amount of time while being exposed to the appropriate environmental conditions. The equipment associated with the EHC 402 can receive the type and size of the valve 100 from the computer system 420 and select a processing software program that will ensure that the valve is immersed to the correct depth, at the correct rate, and remains immersed for the correct amount of time while being exposed to the appropriate environmental conditions. The equipment associated with the chamber 403 can receive the type and size of the valve 100 from the computer system 420 and select a processing software program that ensures that the valve is cured for the proper time under the proper environmental conditions. The equipment associated with the valve cutting can receive the size and type of the valve 100 from the computer system 420 and ensure that the correct program is executed to cut the leaflets 110 (and mandrel 202) in the correct locations. The equipment associated with the cuff sewing system can receive the size and type of the valve 100 from the computer system 420 and ensure that the correct program is executed to sew the sewing cuff to the finished valve prosthesis 100.

[0072] The operation or action can also be moving the valve 100 from one location to another, for example, using an automated transport device 430 to move the valve 100 from the EHC 402 to the chamber 403. This information can inform the transport device 430 of the precise location of the valve 100 (as the valve varies in size). The operation or action can also be measuring the valve 100 and confirming the leaflet measurements (e.g., thickness).

[0073] For example, in some embodiments, prior to or in response to entering a particular manufacturing stage, the valve 100 can be scanned, either automatically or by a human using the automated scanner 900, at step 1054. This information can be relayed, at step 1056, to the computer system 420, which can then output the information, or portions thereof, to the automated manufacturing equipment of the particular manufacturing stage. The information passed to the manufacturing equipment can include additional information not encoded by the identifier 700, such as log files with in-line size measurements or other measured or recorded variables that describe the condition of the valve 100 or the manner in which it has been processed thus far. The manufacturing equipment can utilize this information to set the appropriate processing parameters for processing the valve 100 at the particular manufacturing stage.

[0074] Any measurement data collected by the manufacturing equipment can be relayed back to the computer system 420, which can append to a log file that collected information regarding the particular valve 100. For example, in some embodiments, the identity of the manufacturing equipment, the date and time that the valve 100 was processed by the manufacturing equipment, the length of time that the valve 100 was processed by the manufacturing equipment, environmental conditions (e.g., temperature, pressure, humidity, and the like) recorded by the manufacturing equipment during the processing of the valve 100, and other variables can be output by the manufacturing equipment to the computer system 420 in a manner that associates that information with the identity of the particular valve 100 (or the valve 100 being processed, if concurrent batch processing occurs).

[0075] Upon exiting a given manufacturing stage, the valve 100 can again be scanned to track the location and time of exit of the valve 100. Then, upon reaching the next stage, the valve 100 can again be scanned. This process can be repeated for each manufacturing stage. This can occur one or more times depending on the number of manufacturing stages used to fabricate the valve 100 or the number of manufacturing stages desired for which a specific valve identification is utilized. The valve 100 does not need to be scanned at every stage, e.g., at those stages where there is a linear processing line such that the manufacturing equipment knows with certainty the identity of each valve 100.

[0076] For example, in some embodiments, the valve 100 can be scanned in response to entering a measurement phase. A digital measurement system (DMS) can receive the type, size, and / or serial number of the valve 100 from the computer system 420 to ensure that both the correct measurement program can be selected by the DMS for that particular valve 100 and that the data can be treated as either a master measurement for that valve 100 (e.g., a measurement prior to immersion 306 and leaflet formation) or a thickness measurement (e.g., a measurement after curing 310) from which the thickness of the leaflets 110 can be ascertained.

[0077] Throughout the manufacturing process, output data and the date and time of all operations are persistently recorded on a digital Structured Query Language (SQL) server to create and update a log file (eg, a digital design history record) for the valve 100.

[0078] The embodiments of the valve 100 described herein are suitable for implantation into a patient's body using any number of medical procedures. Preferably, these embodiments of the valve 100 are for direct implantation into the body using open-heart surgery. Such embodiments of the valve 100 are not radially collapsible for insertion into an intravascular (e.g., catheter) or transapical delivery device. However, in other embodiments, the valve 100 can be configured with a radially collapsible support structure 102 that allows the lateral dimensions of the valve 100 to be reduced to a sufficient degree to allow insertion into an appropriately sized intravascular or transapical delivery device.

[0079] Exemplary embodiments of the systems, devices, and methods are described herein with respect to the manufacture of prosthetic heart valves, however, the scope of the disclosure is not so limited and may be applied to prostheses for replacement of other valves outside the heart and elsewhere in a patient's body as well.

[0080] In all embodiments described herein, the automated steps are performed by a processing circuit executing software instructions. The software instructions can be stored in a non-transient memory. The processing circuit and the non-transient memory can be part of a single discrete system, such as a workstation or server, or can be distributed across multiple systems or devices, such as a computer system that accesses information stored remotely across a network. The processing circuit can be a microprocessor, an array of processors, a programmable logic controller (PLC), circuitry distributed across multiple different devices, or otherwise. The non-transient memory can be volatile or non-volatile memory, integrated on the same chip as the processing circuit, a different chip, distributed across multiple chips, or otherwise.

[0081] The embodiments described herein are restated and expanded upon in the following paragraphs without explicit reference to the figures: In a number of exemplary embodiments, a method of valve leaflet manufacturing is provided that includes applying a polymer in a liquid state to a valve frame and a leaflet forming structure, loading the valve frame and the leaflet forming structure with the polymer in the liquid state into a chamber, and automatically moving the valve frame and the leaflet forming structure around the chamber for a period of time during which the polymer at least partially hardens.

[0082] In some embodiments, applying the polymer in a liquid state to the valve frame and leaflet forming structure includes dip coating the valve frame by infiltrating at least a portion of the valve frame and leaflet forming structure into a reservoir filled with the polymer in a liquid state, and removing at least a portion of the valve frame and leaflet forming structure from the reservoir.

[0083] In some embodiments, automatically moving the valve frame and leaflet forming structure around the chamber for a period of time during which the polymer at least partially cures includes automatically rotating the valve frame and leaflet forming structure around the chamber in a plane perpendicular to the axis. The valve frame and leaflet forming structure can be rotated at least one revolution about the axis.

[0084] In some embodiments, the chamber is an environmental humidity chamber (EHC).

[0085] In some embodiments, the method further includes opening a door to the chamber prior to loading the valve frame and the leaflet formation structure, and closing the door to the chamber after loading the valve frame and the leaflet formation structure.

[0086] In some embodiments, automatically moving the valve frame and leaflet forming structure around the chamber comprises moving the valve frame and leaflet forming structure through at least 50% of a cross-sectional area of ​​the chamber.

[0087] In some embodiments, gas is not fanned within the chamber for the period of time.

[0088] In some embodiments, the method further comprises removing the valve frame and the leaflet forming structure from the chamber.

[0089] In some embodiments, the method further includes cutting the excess at least partially cured polymer from the valve frame.

[0090] In some embodiments, the chamber is closed and the valve frame is automatically moved around the chamber and the humidity within the chamber is controlled to ±1%.

[0091] In some embodiments, the chamber has a volume of 1,000 cubic inches or less.

[0092] In some embodiments, the valve frame has an optical identifier thereon.

[0093] In some embodiments, the chamber is a first chamber, and the method further includes removing the valve frame and leaflet forming structure from the first chamber after a period of time, where the polymer is only partially cured, and inserting the valve frame and leaflet forming structure into a second chamber and heating the valve frame and leaflet forming structure in the second chamber until the polymer is cured. The method further includes cutting the cured polymer to form a plurality of leaflets on the valve frame. After removal from the second chamber, the polymer that will form a plurality of leaflets on the valve structure is 70 to 200 microns thick.

[0094] In some embodiments, the valve frame is a first valve frame and the leaflet formation structure is a first leaflet formation structure, and the method further includes applying a polymer in a liquid state to a second valve frame and the second leaflet formation structure, loading the second valve frame and the second leaflet formation structure into a chamber with the polymer in a liquid state, and automatically moving the first valve frame, the first leaflet formation structure, the second valve frame, and the second leaflet formation structure around the chamber for a period of time during which the polymer on the first valve frame, the first leaflet formation structure, the second valve frame, and the second leaflet formation structure at least partially hardens. The method may further include removing the second valve frame and the second leaflet forming structure from the first chamber after a period of time, where the polymer is only partially cured, inserting the second valve frame and the second leaflet forming structure into the second chamber, heating the second valve frame and the second leaflet forming structure in the second chamber until the polymer is cured, and slicing the cured polymer to form a plurality of leaflets on the second valve frame. The thickness variation between each of the plurality of leaflets on the first valve frame and each of the plurality of leaflets on the second valve frame may be less than 10 microns in thickness.

[0095] In many embodiments, a method of valve leaflet manufacturing is provided, the method including the steps of applying a polymer in a liquid state to a valve frame and a leaflet forming structure, loading the valve frame and leaflet forming structure with the polymer in a liquid state into a first chamber and partially curing the polymer while the valve frame and leaflet forming structure are in the first chamber, and loading the valve frame and leaflet forming structure with the polymer in a partially cured state into a second chamber and curing the polymer while the valve frame and leaflet forming structure are in the second chamber.

[0096] In some embodiments, applying the polymer in a liquid state to the valve frame and leaflet forming structure includes dip coating the valve frame by infiltrating at least a portion of the valve frame and leaflet forming structure into a reservoir filled with the polymer in a liquid state, and removing at least a portion of the valve frame and leaflet forming structure from the reservoir.

[0097] In some embodiments, the method further includes automatically moving the valve frame and leaflet forming structure around the first chamber over a period of time during which the polymer partially cures. Automatically moving the valve frame and leaflet forming structure around the first chamber can further include moving the valve frame and leaflet forming structure through at least 50% of a cross-sectional area of ​​the chamber.

[0098] In some embodiments, the method further includes automatically rotating the valve frame and leaflet forming structure around the first chamber in a plane perpendicular to the axis over a period of time during which the polymer partially cures. The valve frame and leaflet forming structure can be rotated at least one revolution about the axis. Automatically rotating the valve frame and leaflet forming structure around the first chamber can include moving the valve frame and leaflet forming structure through at least 50% of a cross-sectional area of ​​the chamber.

[0099] In some embodiments, the first chamber is an environmental humidity chamber (EHC).

[0100] In some embodiments, gas is not fanned in the first chamber for a period of time during which the polymer is partially cured.

[0101] In some embodiments, the method further comprises removing the valve frame and the leaflet forming structure from the chamber.

[0102] In some embodiments, the method further includes cutting excess partially cured polymer from the valve frame prior to loading the valve frame and the leaflet forming structure into the second chamber.

[0103] In some embodiments, when the first chamber and the polymer is partially cured, the humidity in the chamber is controlled to ±1%.

[0104] In some embodiments, the method further includes the step of the first chamber having a volume of 1,000 cubic inches or less.

[0105] In some embodiments, the valve frame has an optical identifier thereon.

[0106] In some embodiments, the method further includes slicing the hardened polymer to form a plurality of leaflets on the valve frame.

[0107] In some embodiments, the valve frame is a first valve frame and the leaflet forming structure is a first valve frame, and the method further includes applying a polymer in a liquid state to a second valve frame and a second leaflet forming structure, loading the second valve frame and the second leaflet forming structure with the polymer in a liquid state into a first chamber and partially curing the polymer while the first valve frame, the first leaflet forming structure, the second valve frame, and the second leaflet forming structure are in the first chamber, and loading the second valve frame and the second leaflet forming structure with the polymer in a partially cured state into a second chamber and curing the polymer while the first valve frame, the first leaflet forming structure, the second valve frame, and the second leaflet forming structure are in the second chamber. The method further includes cutting the cured polymer to form a plurality of leaflets on the second valve frame. The thickness variation between each of the plurality of leaflets on the first valve frame and each of the plurality of leaflets on the second valve frame can be less than 10 microns thick. The method can include removing the valve frame and the leaflet forming structure from the second chamber. After removal from the second chamber, the polymer on the leaflet forming structure can be 70 to 200 microns thick.

[0108] In many embodiments, an apparatus for partially curing a polymer is provided that includes a chamber; a movable fixture within the chamber, the movable fixture including at least one receptacle; a motor coupled to the movable fixture and configured to move the fixture; a humidity sensor within the chamber; a first controllable output within the chamber, the first controllable output configured to controllably dispense a first medium into the chamber; a second controllable output within the chamber, the second controllable output configured to dispense a second medium within the chamber, the first medium having a higher relative humidity than the second medium; and a control system communicatively coupled to the humidity sensor and the first and second controllable outputs, the control system being programmed to control the humidity in the chamber.

[0109] In some embodiments, the receptacle is configured to hold a valve frame or a leaflet forming structure.

[0110] In some embodiments, the movable fixture includes a plurality of receptacles, each of which is configured to hold a valve frame or a leaflet plasty structure.

[0111] In some embodiments, the movable fixture is configured to rotate each receptacle through a plane perpendicular to the axis.

[0112] In some embodiments, the moveable fixture is configured to rotate and the motor is a rotary motor.

[0113] In some embodiments, the moveable fixture is adapted to move the receptacle through at least 50% of a cross-sectional area of ​​the chamber.

[0114] In some embodiments, the apparatus further includes a cutting system. The cutting system can be configured to cut the partially cured polymer.

[0115] In some embodiments, the control system is programmed to control the humidity in the chamber to within ±1% of the humidity setting.

[0116] In some embodiments, the chamber has a volume of 1,000 cubic inches or less.

[0117] In some embodiments, the chamber includes a door. The door can be pneumatically actuable.

[0118] In many embodiments, a method of identifying a prosthetic valve is provided, the method including the steps of marking a valve frame of the prosthetic valve with an identifier, coating the valve frame and the identifier with a coating agent, and reading the identifier through the coating, where the identifier is read by a machine.

[0119] In some embodiments, reading the identifier includes reading, by the scanning device, information encoded in the identifier and automatically communicating the information from the scanning device to the computer system via the communication coupling. The scanning device can include a processing circuit and a non-transient memory on which a plurality of instructions are stored that, when executed by the processing circuit, cause the processing circuit to communicate the information from the scanning device to the computer system. The method can further include processing, by the computer system, the information received from the scanning device and outputting corresponding information to the manufacturing device. The method can further include automatically selecting, by the manufacturing device, a software program, function, or parameter for performing an operation or action on the prosthetic valve based on the corresponding information. The computer system can include a processing circuit and a non-transient memory on which a plurality of instructions are stored that, when executed by the processing circuit, cause the processing circuit to process the information received from the scanning device and outputting corresponding information to the manufacturing device. The manufacturing equipment can include a processing circuit and a non-transient memory having a plurality of instructions stored on the non-transient memory that, when executed by the processing circuit, causes the processing circuit to automatically select a software program for performing a manufacturing operation on the valve based on the corresponding information.

[0120] In some embodiments, the identifier is optically readable. The identifier can be at least one of a one-dimensional code, a two-dimensional code, a three-dimensional code, and an optically recognizable sequence of alphanumeric or symbolic characters.

[0121] In some embodiments, the identifier is a QR code.

[0122] In some embodiments, the identifier represents information about the valve prosthesis. The information can include at least one of a valve type, a valve size, or a serial number. The information can include a valve type, a valve size, and a serial number. The valve type can be either an aortic valve or a mitral valve. The valve size can be one of 17 mm, 19 mm, 21 mm, 23 mm, 25 mm, 27 mm, or 29 mm.

[0123] In some embodiments, the method further includes automatically selecting a software program, function, or parameter for an automated operation or action to be performed on the valve prosthesis based on the information read from the identifier. The software program, function, or parameter can be for applying a polymer to the coated valve frame and leaflet formation structure, the polymer for forming a plurality of leaflets. The method can further include reading the identifier through the coating and the polymer. The software program, function, or parameter can be for an automated first phase of curing the polymer on the valve frame and the leaflet formation structure. The software program, function, or parameter can be for an automated second phase of curing the polymer on the valve frame and the leaflet formation structure. The software program, function, or parameter can be for cutting the cured polymer and forming a plurality of leaflets on the valve frame. The software program, function, or parameter can be for measuring a plurality of leaflets on the valve frame. The software program, function, or parameter can be for automatically transporting the valve frame between manufacturing stages. The software program, function, or parameter can be for finishing the valve frame.

[0124] In many embodiments, a prosthetic valve is provided that includes a frame having an identifier thereon, where the identifier is machine readable, and a plurality of polymeric leaflets integrally joined to the frame by a layer of polymer, where the layer of polymer covers the identifier and where the identifier remains machine readable through the layer of polymer.

[0125] In some embodiments, the identifier represents at least a unique identifier of the prosthetic valve.

[0126] In some embodiments, the identifier represents at least a serial number of the prosthetic valve.

[0127] In some embodiments, the identifier represents at least a unique identifier and a type of prosthetic valve.

[0128] In some embodiments, the identifier represents at least a unique identifier and a size of the prosthetic valve.

[0129] In some embodiments, the identifier represents at least a unique identifier, a type of prosthetic valve, and a size of the prosthetic valve.

[0130] In some embodiments, the identifier is an optically readable identifier. The identifier can be at least one of a one-dimensional code, a two-dimensional code, a three-dimensional code, and an optically recognizable sequence of alphanumeric or symbolic characters. The optical identifier can be a QR code.

[0131] In some embodiments, the frame and identifier are covered with a coating and a layer of polymer over the coating, and the identifier remains machine readable through both the coating and the layer of polymer.

[0132] In some embodiments, the identifier is readable using radio frequency (RF) energy.

[0133] In some embodiments, the prosthetic valve is a prosthetic heart valve. The identifier may represent at least a type of prosthetic heart valve. The type of prosthetic heart valve may be either an aortic valve or a mitral valve.

[0134] Various aspects of the subject matter are described below in the context of and / or as a complement to the previously described embodiments, with emphasis placed on the interrelationship and mutual compatibility of the following embodiments, in other words, on the fact that each feature of the embodiments can be combined with every other feature, unless expressly stated otherwise or logically possible.

[0135] Those skilled in the art will, in light of this description, readily recognize many variations of suitable immersion casting techniques, pressures, and temperatures not mentioned herein that are suitable for fabricating the prosthetic heart valves described herein. Likewise, those skilled in the art will also, in light of this description, recognize alternatives to immersion casting that may be used to fabricate the prosthetic heart valves described herein.

[0136] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0137] Where a range of values ​​is provided, unless the context clearly dictates otherwise, each intervening value, to the nearest tenth of the lower limit between the upper and lower limits of that range, and any other stated or intervening value within that stated range, is included within the disclosure and can be claimed as a single value or as a smaller range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included in the limits are also included within the disclosure.

[0138] When a discrete value or range of values ​​is provided, the value or range of values ​​may be claimed more broadly than as a discrete number or range of numbers, unless otherwise indicated. For example, each value or range of values ​​provided herein may be claimed as an approximation, and this paragraph serves as a preamble and descriptive aid for the introduction of claims, always listing each such value or range of values ​​as "approximately" that value, "approximately" that value range, "about" that value, and / or "about" that value range. Conversely, when a value or range of values ​​is stated as an approximation or generalization, for example, approximately X or about X, the value or range of values ​​may be claimed discretely, without using such an expanding term.

[0139] However, this specification should not be construed in any way as implying that the subject matter disclosed herein is limited to a particular value or range of values, unless there is an express recitation of that value or range of values ​​in a claim. Values ​​and ranges of values ​​are provided herein merely as examples.

[0140] It should be noted that all features, elements, components, functions, and steps described with respect to any embodiment provided herein are intended to be freely combinable and substitutable with those from any other embodiment. When a feature, element, component, function, or step is described with respect to only one embodiment, it should be understood that the feature, element, component, function, or step can be used with any embodiment described herein, unless expressly stated otherwise. This paragraph therefore always serves as a predicative basis and descriptive aid for the introduction of claims combining features, elements, components, functions, and steps from different embodiments or substituting features, elements, components, functions, and steps from one embodiment with those of another embodiment, even if the following description does not expressly state that such combinations or substitutions are possible in a particular case. It is clearly recognized that an explicit enumeration of all possible such combinations and substitutions would be unduly burdensome, especially with the premise that the acceptance of all combinations and substitutions would be easily recognized by those skilled in the art.

[0141] While the embodiments are susceptible to various modifications and alternative forms, specific examples thereof are shown in the drawings and described in detail herein. However, it should be understood that these embodiments are not limited to the particular forms disclosed, but on the contrary, these embodiments should cover all modifications, equivalents, and alternatives falling within the spirit of the present disclosure. Furthermore, any feature, function, step, or element of the embodiments may be recited in or added to the claims, with negative limitations defining such scope by any feature, function, step, or element that does not fall within the scope of the claimed invention.

[0142] Other systems, devices, methods, features, and advantages of the subject matter described herein will be, or will become, apparent to one of ordinary skill in the art upon review of the following figures and detailed description. All such additional systems, devices, methods, features, and advantages are intended to be included within this description, be within the scope of the subject matter described herein, and be protected by the accompanying claims. Features of the example embodiments are not to be construed in any way as limiting the appended claims unless there is an express recitation of those features in the claims.

Claims

[Claim 1] The invention as depicted in the drawings of this application.

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