Patent Description:
The human heart has a number of valves for maintaining the flow of blood through the body in the proper direction. The major valves of the heart are the atrioventricular (AV) valves, including the bicuspid (mitral) and the tricuspid valves, and the semilunar valves, including the aortic and the pulmonary valves. When healthy, each of these valves operates in a similar manner. The valve translates between an open state (that permits the flow of blood) and a closed state (that prevents the flow of blood) in response to pressure differentials that arise on opposite sides of the valve.

A patient's health can be placed at serious risk if any of these valves begin to malfunction. Although the malfunction can be due to a variety of reasons, it typically results in either a blood flow restricting stenosis or a regurgitation, where blood is permitted to flow in the wrong direction. If the deficiency is severe, then the heart valve may require replacement.

Substantial effort has been invested in the development of replacement heart valves, most notably replacement aortic and mitral valves. Replacement valves can be implanted percutaneously by way of a transfemorally or transapically introduced catheter, or can be implanted directly through open heart surgery. The replacement valves typically include an arrangement of valve leaflets that are fabricated from porcine tissue. These tissue leaflets are highly distensible or stretchable and manufacture of the valves involves manually sewing the leaflets to a support.

<CIT> relates to a compressible prosthetic heart valve having a stent with three leaflets a ring-like body defining three arch-shaped elements including an arc and a pair of opposing haunches and three commissural posts formed by the haunches and adjacent elements. The leaflets each have an attachment edge and a free edge with a belly extending therebetween. The leaflets are movable between a coapted condition, in which the free edges abut and prevent fluid flow through the valve, and an open condition, in which fluid flow through the valve is permitted. The leaflets are made from a polymeric material and are created on a mold to which polymer is applied. This document separately discloses temperature and humidity parameters for spraying polymer directly onto a mold and temperature parameters for dipping a mold into polymer.

<CIT> discusses a single-layer tissue sheet having a puncture strength of <NUM> kgf to <NUM> kgf. A heart valve may be made from one or more leaflets formed from a single-layer tissue sheet. A method of making a tissue sheet having a puncture strength of <NUM> kgf to <NUM> kgf is described having very long culture times, such as in excess of <NUM> weeks. Valves that comprise one or more leaflets made from the ultra-strong tissue sheets may be delivered via trans-catheter aortic valve implantation. This document does not disclose any particular structures or manufacturing parameters for forming structural or leaflet materials from polymers.

<CIT> relates to a collapsible stent for an implantable prosthetic valve incorporates leaflet-supporting members having relatively large surface area in comparison to other members defining the remainder of the stent. The leaflet-supporting members may have openings extending through them. The valve leaflets may be attached to the stent so that an attached edge of each leaflet extends along the leaflet-supporting members and is attached to the members by polymer integral with the leaflet overlying the leaflet supporting members and extending into the openings of the leaflet supporting members. The valve structure may be formulated from a flowing polymer that is then cured. This document does not disclose any particular structures or manufacturing parameters for forming the leaflets or leaflet-supporting members.

<CIT> describes a mandrel used to form a valve leaflet and support structure and describes a conventional housing and polymer solvent removal conditions traditionally used with polymer coating methods. In this document, the polymer applied to the valve mandrel, frame or assemble is maintained in a heat chamber to dry off the solvent.

Other replacement valves have artificial polymeric leaflets integrally formed to a support structure. While 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.

For these and other reasons, needs exist for improved systems, devices, and methods for manufacturing prosthetic valves with artificial leaflets.

Provided herein are a number of example embodiments of systems, devices, and methods for manufacturing or use in manufacturing a prosthetic heart valve. Many of these embodiments can utilize an environmental humidity chamber (EHC) during a phase of partially curing liquid polymer that will, after further processing, form leaflets on a valve frame. The EHC can be part of a multiple stage manufacturing process and, in some embodiments, the multiple stages can include applying the liquid polymer to the valve frame and a leaflet formation structure, then partially curing the liquid polymer in the EHC, and then removing the valve frame and leaflet formation structure and subjecting the partially cured polymer to another stage of curing. Variations to this process and additional steps can be implemented as well.

Also provided herein are a number of example embodiments of systems, devices, and methods for utilizing an identifier applied to a valve frame during a manufacturing process. The identifier can represent information about the valve or valve frame, and can be read using one of a number of various energy spectrums. In some embodiments, the identifier is an optically readable bar code or QR code. In some embodiments, the identifier includes a serial number or other unique identifier of the valve frame, a type of the valve or valve frame, and/or a size of the valve or valve frame. The identifier can be applied to the valve frame prior to the 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 a manufacturing process and after. The identifier can be used to select the appropriate software for manufacturing the valve at various stages of the manufacturing process.

Other systems, devices, methods, features and advantages of the subject matter described herein will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description, be within the scope of the subject matter described herein. In no way should the features of the example embodiments be construed as limiting the appended claims, absent express recitation of those features in the claims.

The details of the subject matter set forth herein, both as to its structure and operation, may be apparent by study 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, where relative sizes, shapes and other detailed attributes may be illustrated schematically rather than literally or precisely.

Before the present subject matter is described in detail, it is to be understood that this disclosure is not limited to the particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

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

The example 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> is a perspective view depicting an example of a prosthetic valve <NUM> having frame <NUM> and three valve leaflets <NUM>-<NUM>, <NUM>-<NUM>, and <NUM>-<NUM>. Valve <NUM> is configured to allow blood to flow from an upstream end <NUM> to a downstream end <NUM>. Frame <NUM> has an annular base portion <NUM> that can have a planar or flat upstream terminus (not shown) or a curved or scalloped upstream terminus as shown here. Frame <NUM> also includes three extensions <NUM> that project from annular base portion <NUM> towards downstream end <NUM>.

The downstream edges of extensions <NUM> have curved interfaces <NUM>, which are the locations where support structure <NUM> meets the operable base of leaflets <NUM>. Leaflets <NUM> each have a free edge <NUM>, and leaflets <NUM> are free to move with respect to support structure <NUM> between open and closed positions for permitting and preventing, respectively, the flow of blood through valve <NUM>. Each of leaflets <NUM> can be discrete from the others (as shown here) or can be portions of one unitary (monolithic) leaflet body. Leaflets <NUM> are integrally formed on this frame <NUM>, such as through a casting (e.g., dip casting) or molding process.

Annular base portion <NUM> also includes flanges <NUM> and <NUM> between which a sewing cuff (not shown) can be placed. In other valves <NUM>, only a single flange <NUM> may be present, or the flanges <NUM> and <NUM> can be omitted altogether. Examples of valves with sewing cuffs are described in <CIT>, <CIT>, <CIT>, and <CIT>. Other examples of prosthetic heart valves are described, for instance, in International Patent Application Publication No. <CIT>, and <CIT>.

Frame <NUM> 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 materials are preferably polymeric materials such as polyether ether ketones (PEEK), polyurethanes, a polyetherimides (PEI) such as ULTEM, any of the materials used to form leaflets <NUM>, and others. Leaflets <NUM> are also preferably fabricated from polymeric materials, including any biostable polyurethanes and polyurethane compositions (e.g., polysiloxane-containing polyurethanes, etc.) known in the art. Examples of polyurethane-containing leaflets are described in <CIT>, <CIT>, <CIT>, <CIT> ("Polyurethane/urea Compositions"), and <NPL>). Materials that approach ideal isotropic non-creeping characteristics are particularly suitable for use in many embodiments.

Numerous embodiments of systems, devices, and methods of manufacturing valves <NUM> having artificial polymeric leaflets <NUM> are described herein. Valves <NUM> are manufactured in a fashion that integrates leaflets <NUM> directly with frame <NUM> in a seamless manner, such as by coating a mandrel holding frame <NUM> with the polymer in liquid form. Thus, the same step of forming the leaflets also couples them to frame <NUM>. The manufacturing embodiments will be described herein in the context of a dip casting or dipping process used to form the leaflets, however those of ordinary skill in the art will recognize that other formation processes (e.g., molding) can be used as well.

<FIG> is a photograph depicting an example of a frame <NUM>, with a single flange <NUM>, prior to formation of leaflets <NUM>. <FIG> is a photograph depicting an example of a valve former or formation structure, also referred to as a mandrel <NUM>, suitable for use in a dip casting method. In this example, mandrel <NUM> is sized to receive frame <NUM> at middle (or frame) portion <NUM>, which has an exterior surface dimensioned to match the interior surface of frame <NUM>, and also dimensioned to allow formation of leaflets thereon. The dimensions of middle portion <NUM> are varied depending on the size of frame <NUM> and the size (e.g., <NUM>, <NUM>, <NUM>, etc.) and type of valve (e.g., aortic, mitral, or other) being manufactured. Mandrel <NUM> has a base portion <NUM> that can be grasped by manufacturing equipment during the manufacturing process. Base portion <NUM> can thus have uniform dimensions that are the same regardless of what size valve is being manufactured. During a dipping process mandrel <NUM> would be inverted from the orientation shown in <FIG>, and a tip portion <NUM> (which would thus be located at bottom) of mandrel <NUM> can be present to guide polymer runoff after frame <NUM> and mandrel <NUM> are dipped into a container of liquid polymer.

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

The leaflets can then be formed at step(s) <NUM>. As stated herein, leaflet formation can occur in multiple ways and a dip casting process will be described as an example. Frame <NUM> can first be placed over mandrel <NUM> (if not already). Mandrel <NUM> (with frame <NUM> thereon) can then be inserted into a reservoir having the leaflet material in a liquid state (e.g., as a solution including solvent). Mandrel <NUM> is preferably dipped such that the solution envelops tip portion <NUM> and middle portion <NUM> of mandrel <NUM>, including envelopment of frame <NUM> thereon. Mandrel <NUM> can be submersed further such that some or all of base portion <NUM> is covered as well. This dipping process preferably takes place under a relatively high temperature and high humidity. Although the methods disclosed herein are not limited to such, in some example embodiments, the relative humidity (RH) can be in the range of <NUM>-<NUM>% and the temperature can be in the range of <NUM>-<NUM> degrees C.

Upon removal from the reservoir, frame <NUM> and mandrel <NUM> (including the leaflet casting surfaces) will be covered in a layer of liquid polymer and this layer can drip or runoff along portion <NUM> of mandrel <NUM>. The dipping step <NUM> can be performed only once to arrive at the fully formed (but unfinished) valve <NUM>, or can be performed multiple times (e.g., two times, three times, or as many times as desired). If multiple dipping steps are performed, then the dipping can occur into a reservoir with polymer having the same or a different viscosity.

After dipping is complete, mandrel <NUM> and valve <NUM> can be subjected to a first phase of curing at step <NUM>, followed by a second phase of curing <NUM>. The first phase of curing <NUM> can be a relatively short cure lasting a few minutes, and the second phase of curing <NUM> can be a relatively longer cure lasting several hours. The first phase of curing <NUM> can be performed within an environmental humidity chamber (EHC) that will be described in greater detail herein. Although purposes for performing the first phase of curing can vary, in many cases this first phase <NUM> is performed at process conditions that cause the liquid polymer to reach a viscosity or level of dryness sufficient to substantially slow or stop runoff or dripping, sometimes referred to as causing the leaflets to seize. The level of runoff impacts the thickness of the resulting leaflets <NUM>, and thus their performance characteristics, making it desirable to maintain a high degree of control during manufacturing.

After first phase <NUM>, excessive seized polymer can be trimmed if needed and valve <NUM> can be subjected to a second phase of curing <NUM>. The second phase <NUM> can take place in a different chamber, such as an oven, and can cause the seized polymer to complete the drying process.

After curing step <NUM>, valve <NUM> can be subjected to one or more finishing processes at <NUM>, such as one or more of removal of mandrel <NUM>, trimming, sewing cuff attachment, inspection, packaging, or the like. For example, leaflets <NUM> (and optionally frame <NUM>) can be trimmed and/or otherwise finished to achieve accurate and precise edges and surface smoothness. This can occur, for example, through laser cutting, ultrasonic trimming, a water knife, a mechanical clam shell cutter, and the like. In some embodiments, valve <NUM> is trimmed while on mandrel <NUM> by cutting through the leaflet polymer and mandrel at the intersection between middle portion <NUM> and tip portion <NUM> of mandrel <NUM>. A sewing cuff can be coupled with valve <NUM> (using any flange if present) if desired. Valve <NUM> can be subjected to a visual inspection and/or measurement. Valve <NUM> can then be packaged in the desired sterile container.

<FIG> is a flow diagram depicting an example embodiment of method <NUM> of forming leaflets <NUM> for a prosthetic valve <NUM>. Here, method <NUM> includes the steps of dipping <NUM>, first phase curing <NUM>, and second phase curing <NUM>, substantially as described with respect to the embodiment of <FIG>. The remaining steps of method <NUM>, while they can be included, are optional to method <NUM>.

<FIG> are block diagrams depicting example embodiments of manufacturing facilities <NUM> for valve <NUM>. Facility <NUM> is preferably configured as a sealable clean environment with an internal environment <NUM> that is controlled with filtered airflow passageways entering facility <NUM> to limit or prevent particle contamination. The temperature, humidity, ambient pressure, and composition of the ambient gas (e.g., oxygen level, nitrogen level, etc.) within environment <NUM> can also be controlled and maintained at a desired level by environment control equipment <NUM>. A computer system <NUM> having processing circuitry <NUM> executing control software stored in a non-transitory memory <NUM> can be communicatively coupled with control equipment <NUM> and can exercise control over equipment <NUM>, and thus environment <NUM>. Processing circuitry <NUM> can be one or more processors, controllers, programable logic controllers (PLCs), a combination thereof, and the like.

Facility <NUM> can include one or more internal chambers in which certain steps of valve manufacturing can be performed. The size of facility <NUM> can vary, and in some embodiments is only <NUM>-<NUM> meters in width by <NUM>-<NUM> meters in length. In the embodiment of <FIG>, facility <NUM> includes a first chamber <NUM> for performing dipping step <NUM>, a second chamber <NUM> for performing first phase curing step <NUM>, and a third chamber <NUM> for performing second phase curing step <NUM>. Other chambers can be included for performance of other manufacturing steps if desired.

Each chamber <NUM>-<NUM> has its own internal environment that can be controlled independently of the environments within the other chambers and within the ambient space <NUM> of facility <NUM>. Control of the internal environment of each chamber <NUM>-<NUM> can include control of temperature, humidity, composition of the internal gas, ambient gas pressure, and the like. Control of the internal environment of each chamber <NUM>-<NUM> can be performed automatically by software executed by processing circuitry <NUM> of master computer system <NUM>, that is communicatively coupled with environmental control equipment <NUM>-<NUM> of each chamber <NUM>-<NUM>, respectively. In the embodiment of <FIG>, separate chambers <NUM> and <NUM> are present for curing steps <NUM> and <NUM>, but dipping step <NUM> is performed in the ambient environment <NUM> of facility <NUM>. In some embodiments, dipping can be performed within EHC <NUM>.

In the embodiments of <FIG>, automated equipment <NUM> (e.g., robotic equipment) can be included for transferring frame <NUM> (with or without leaflets <NUM>) from each location or chamber <NUM>-<NUM> to the next. Automated equipment <NUM> can also be communicatively coupled with and under the control of computer system <NUM>.

Referring back to first phase of curing <NUM> of methods <NUM> and <NUM>, second chamber <NUM> can be configured as an environmental humidity chamber (EHC) <NUM>. <FIG> are photographs of an example embodiment of an EHC <NUM>. <FIG> is a front view of EHC <NUM>, <FIG> is a front view of EHC <NUM> with an example embodiment of mandrel <NUM> having a valve <NUM> thereon, <FIG> is a side view of EHC <NUM> with mandrel <NUM> and valve <NUM>, and <FIG> and <FIG> are top down views of EHC <NUM> during rotation of mandrel <NUM> with valve <NUM>. In some embodiments the leaflet polymer is transparent or translucent and thus, if frame <NUM> has been dipped, the presence of leaflets <NUM> may not be readily visible.

EHC <NUM> is a closeable chamber with one or more automatic doors <NUM> controllable for insertion and removal of valves <NUM>. Immediately after dipping step <NUM>, valve <NUM> (frame <NUM> with wet polymer in the form of nascent leaflets <NUM>) and mandrel <NUM> can be inserted through door <NUM> into a holder, receptacle, or station <NUM> within the interior space <NUM> (the processing space between the walls, floor and ceiling) of EHC <NUM>, as shown in <FIG>. In some embodiments, door <NUM> is a piston activated, or pneumatic, slide door. Door <NUM> can transition from closed to open and vice versa relatively quickly, for example, in about <NUM> seconds or less, which can ensure that the humidity level does not vary significantly when opened to the ambient atmosphere <NUM> of facility <NUM>. In addition, the small volume of the EHC <NUM> allows for rapid recovery of the relative humidity level to a desired set level.

EHC <NUM> can include one or more environmental sensors <NUM> (<FIG>) for measuring temperature, humidity, pressure, or other factors. EHC <NUM> can be capable of controlling or maintaining the level of humidity within the internal space <NUM> with high precision. For example, in certain embodiments, the humidity in EHC <NUM> may be controlled to remain in a range of about ± <NUM>% while valve <NUM> is in EHC <NUM> in closed state. The length of exposure of valve <NUM> within space <NUM> can be timed with high precision. For example, the exposure time can be controlled by processing circuitry <NUM>.

The control of both the humidity level and exposure time can be critical to the manufacture of leaflets <NUM> with the desired thickness. It has been shown that leaflets <NUM> on the same valve <NUM> processed within EHC <NUM> can, when measured after final curing (e.g., after removal from second chamber <NUM> during a subsequent inspection) have leaflet thickness that are within <NUM> microns (or less) (e.g., <NUM>-<NUM> microns) of each other (i.e., leaflet-to-leaflet thickness variation on a single valve is less than <NUM> microns). This is for leaflets that are generally fabricated to have a final thickness in the range between <NUM> and <NUM> microns. In some embodiments it has been found that close control of these factors can result in repeatable valve leaflets with mean thicknesses within <NUM>-<NUM> microns of each other. In contrast, prosthetic heart valves made with tissue leaflets often have a leaflet-to-leaflet variation of <NUM> microns.

In some embodiments, the relative humidity (RH) within EHC <NUM> can be in the range of between about <NUM>% to about <NUM>%, or about <NUM>% to about <NUM>%, and more preferably, between about <NUM>% to about <NUM>%. In some embodiments, the exposure time can be between about <NUM> minutes to <NUM> minutes, or about <NUM> minutes to <NUM> minutes, and more preferably, between about <NUM> minutes to <NUM> minutes.

EHC <NUM> can include a movable fixture <NUM> having one or more (in this example four) holders <NUM>, each configured to grasp and/or hold a mandrel <NUM> while valve <NUM> is situated thereon with wet polymer. In other embodiments, holders <NUM> can hold valve <NUM> directly. A motor <NUM> can move fixture <NUM> while valves <NUM> are within holders <NUM>. In <FIG>, two of the four holders <NUM> are empty, one holder <NUM> is occupied by mandrel <NUM>, and the other holder <NUM> is hidden from view. In this embodiment, fixture <NUM> includes a plate or shelf coupled to an axle, and the axle is coupled to motor <NUM>, which is configured to rotate the axle and plate while mandrels <NUM> are placed thereon so that, e.g., each valve <NUM> experiences the same average environmental exposure within EHC <NUM>. Mandrels <NUM> in fixture <NUM> can be moved in a plane perpendicular to the axis of rotation around EHC <NUM> (<FIG>), during which moving the polymer deposited on frame <NUM> and mandrel <NUM> partially cures. As they rotate around a path, for example, of about <NUM> (<NUM> inches) in diameter, they mark-out a cylindrical space occupying approximately <NUM>% of the cross-sectional area of EHC <NUM>. Viewed in this fashion, in some embodiments, at least about <NUM>% of the cross section can be covered. In some embodiments, one to four stations <NUM> can concurrently process valves <NUM>, but in other embodiments more than four stations <NUM> can be used concurrently.

During rotation, liquid polymer can runoff from mandrels <NUM>, and can result in long strands of semi-solidified polymer that extend from the base of mandrel <NUM>, sometimes all the way to the floor of EHC <NUM>. EHC <NUM> can be equipped with an automated cutting or knife system <NUM> (<FIG>) that can be used to trim this excessive drip, either by cutting in the location shown in <FIG>, by lowering valve <NUM> to this location, or by raising cutting system <NUM> to the terminus of tip portion <NUM> of mandrel and cutting there. This minimizes further potential dripping or spillage or distortion to leaflets <NUM> during the second curing process <NUM>.

In some embodiments, the duration of rotation can range from about <NUM> to <NUM> minutes per cycle, such as <NUM>, <NUM>, or <NUM> minutes per cycle. During this time each valve <NUM> can be rotated once or more about the interior of EHC <NUM>. In certain embodiments, each valve <NUM> can be rotated about <NUM> degrees (two rotations) in approximately <NUM> minutes or less. This was found to result in highly consistent inter leaflet and intra valve leaflet thickness. For example, in certain embodiments, the standard deviation across three leaflets <NUM> was in the range of about <NUM>-<NUM> microns, whereas without rotation, one of the leaflets was found to be consistently systematically thicker that the other two by as much as <NUM> microns on average.

Interior space <NUM> of EHC <NUM> can have a relatively small volume. For example, inner space <NUM> of EHC <NUM> can be approximately <NUM> x <NUM> x <NUM> (<NUM> x <NUM> x <NUM> inches). By way of reference, some conventional approaches utilize a manufacturing chamber of approximately <NUM> x <NUM> x <NUM> (<NUM> x <NUM> x <NUM> inches) in which multiple steps of valve manufacturing are concurrently performed in the same ambient atmosphere. Inner space <NUM> of EHC <NUM> can have a volume, in some embodiments, of <NUM>,<NUM> cubic cm (<NUM> cubic inches) or less. This smaller volume and purpose-dedicated EHC <NUM> can allow for more precise control of the relative humidity (RH) level and greater homogeneity of the layer of polymer used to form leaflets <NUM>.

In some embodiments, humidity in EHC <NUM> can be controlled by a variable mixture of relatively dry and wet mediums such as, for example, nitrogen and distilled water. EHC <NUM> can include a controllable output <NUM> for the dry medium and a controllable output <NUM> for the relatively wet medium. In certain embodiments, the dry medium (e.g., nitrogen) can be supplied to EHC <NUM> at a level of between about <NUM> to <NUM> liters/min, or preferably at about <NUM> liters/min. The supply can be pressurized and, while a fan can be used in some cases, EHC <NUM> can be configured such that no gas is fan-driven within EHC <NUM> during the curing. The supply of dry medium can be bifurcated and fed to both outputs <NUM> and <NUM> (<FIG>). The dry medium can have an RH from <NUM>-<NUM>% and be fed into interior space <NUM> to lower humidity. The wet medium (e.g., a combination of the dry medium and water) can be fed to interior space <NUM> and used to raise humidity A shield or cover <NUM> can be placed over outputs <NUM> and <NUM> to prevent the dry or wet mediums from coming into direct contact with the curing polymer. Such an approach can ensure the optimal operation and rapid recovery of the humidity (RH) to the desired set point. Control equipment <NUM> can be communicatively coupled with sensor <NUM> and can control outputs <NUM> and <NUM> to maintain humidity within about ± <NUM>% of a target level. Control equipment <NUM> can also control and maintain the temperature within EHC <NUM> at a target level.

For manufacturing consistent nominal valves <NUM>, some of the optimum parameters for certain embodiments were determined to be as follows: <NUM>% RH and a <NUM> minute exposure time for <NUM> and <NUM> aortic valves, <NUM>% RH and a <NUM> minute exposure time for <NUM> aortic valves, <NUM>% RH and a <NUM> minute exposure time for <NUM> aortic valves, <NUM>% RH and a <NUM> minute exposure time for <NUM> aortic valves, and <NUM>% RH and a <NUM> minute exposure time for <NUM> aortic valves. Of course, the embodiments of systems, devices, and methods described herein are not limited to the described processing parameters as such can and will vary depending on the specifics of the implementation.

Computer system <NUM> and/or control equipment <NUM> can cause door <NUM> to open and close. System <NUM> and/or equipment <NUM> can also control the triggering or initiation of the rotation sequence, the speed of rotation and duration of exposure within EHC <NUM>, the control of the environment within EHC <NUM> (e.g., operation of humidity adjustment lines <NUM> and <NUM>), process readings from humidity sensor <NUM>, and the operation of cutting system <NUM>. When the exposure period is over, system <NUM> and/or equipment <NUM> can cause door <NUM> to be opened and each valve <NUM> to be removed by automated transfer equipment <NUM>, and then transferred to the next stage, e.g., chamber <NUM>, for second phase curing <NUM>. Automated transfer equipment <NUM> can then transfer valves <NUM> out of facility <NUM> so that finishing and other processes can be performed on each valve <NUM> and the manufacturing process can be completed.

In the manufacturing embodiments described herein, as well as other manufacturing methods, an identifier can be applied, placed, or marked on a surface of frame <NUM> or valve <NUM>. This identifier can represent information about the frame <NUM> or valve <NUM>. The identifier is machine-readable, and can convey information via optical, infrared, or ultraviolet codes, or by radio frequency (RF) energy (e.g., an RFID or Near Field Communication (NFC) tag) or others.

In many embodiments, the identifier can be applied to the surface of frame <NUM> prior to application of the leaflet coating (e.g., through dip-coating step <NUM>) and application of the leaflet undercoating (e.g., coating step <NUM>) if one is applied. The one or more coatings can be relatively thin and/or can be translucent or transparent to optical light (or other frequencies of energy). The identifier can be visually, optically, and/or otherwise read through the overlying coating(s) and used to trace (e.g., mark the time and location of) frame <NUM> 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 in order to for the manufacturing equipment (e.g., automated transfer equipment <NUM>, chambers <NUM>-<NUM>) to load and execute software instructions particular to the manufacturing of each specific valve <NUM>.

<FIG> is a photograph depicting an example embodiment of an unmarked frame <NUM> (e.g., a blank frame) in a fixture <NUM> (e.g., etching jig) used to hold frame <NUM> during application of an identifier marking directly to frame <NUM>. <FIG> is a photograph depicting an example embodiment of a frame <NUM> after being marked with an optically scannable identifier <NUM>. Various types of marking devices can be used that mark frame <NUM> with identifier <NUM> directly in or on the surface of frame <NUM>. In some embodiments, the marking may be done by etching the surface, by applying heat so as to change the surface coloring, by applying a die or ink or other substance that is visually distinguishable from the surface of the frame <NUM>, or any other suitable means of marking or a combination thereof.

In some embodiments, a carrier having identifier <NUM> thereon can be applied to the frame <NUM>, such as a printed flexible patch or plate. In some embodiments, the carrier can be fastened to valve <NUM> using adhesive, bonding, a mechanical fixing member, or any combination thereof. Identifiers <NUM> that are another a substrate that can be fastened to frame <NUM> are particularly suitable when identifier <NUM> is in the form of an RFID or NFC tag.

In the embodiment of <FIG>, identifier <NUM> is in the form of a QR code and can be seen by virtue of its darker shading than the surface of frame <NUM> itself. <FIG> is a photograph depicting frame <NUM> with identifier <NUM> in more detail. <FIG> is a photograph depicting a process of reading identifier <NUM> using reader device <NUM>, which in this embodiment is a scanner or camera for reading optical codes and/or texts. For example, the QR code can be read by a Cognex barcode scanning camera. In some embodiments, when the QR code is scanned, the read information is conveyed from scanner <NUM> to computer system <NUM> communicably connected thereto by a communicative coupling (which may be wired, or more preferably, wireless). The information read by reader device <NUM> can be processed or decoded by computer system <NUM>.

Identifier <NUM> preferably identifies the individual valve <NUM> with enough specificity to distinguish that individual valve <NUM> from all other valves being processed by a particular piece of manufacturing equipment during a particular timeframe. Such an identifier <NUM> can be referred to herein as a "valve-specific identifier. " For example, in certain embodiments, identifier <NUM> can be a unique identifier that has not been used with any other valve that has been processed by a piece of manufacturing equipment. In some embodiments, the identifier <NUM> can be recycled, so long as it is not reused within a time period in which the identity of two different valves <NUM> may be confused. In some embodiments, identifier <NUM> can be or include a unique serial number for the valve <NUM>.

In some embodiments, identifier <NUM> can also include other information, such as "type" information that can include the identity of the native valve for which the prosthesis valve <NUM> serves as a replacement (e.g., aortic, mitral, etc.). In some embodiments, identifier <NUM> can include the size of valve <NUM> (e.g., <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, etc.). In certain embodiments, identifier <NUM> includes a valve-specific identifier, type information (e.g., aortic, mitral, etc.), and size information (e.g., <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, etc.). In certain embodiments, identifier <NUM> can include other information such as the type of material(s) being used to form the valve, or the type of surgical procedure in which the valve <NUM> may be used/recommended. In some embodiments, identifier <NUM> can omit a unique identifier and include only this "type" information.

In some embodiments, identifier <NUM> will at least uniquely identify valve <NUM> in all significant manufacturing stages that occur after association of identifier <NUM> with valve <NUM>. Furthermore, in some embodiments, identifier <NUM> can be read after manufacturing is complete, i.e., post-manufacturing, such as after valve <NUM> has been distributed from the manufacturer to a distributor or other party responsible for selling valve <NUM> to the medical professional. Thus, any other third-party that comes into possession of valve <NUM> (e.g., distributor, retailer, shipper, medical professional, hospital, government agency, etc.) can read and utilize identifier <NUM> for tracking, inventory, analysis of clinical test results, or any other suitable purposes. The identity of valve <NUM> can be traced to the surgical procedure if read by medical professional or hospital having that capability. Thus, the identity of valve <NUM> can be associated with an identifier for a particular patient, such that performance of valve <NUM> in situ can be traced all of the way back to manufacturing stages. The identity of valve <NUM> can be ascertained after its removal from a patient, such as by any party capable of reading identifier <NUM>, or by shipment of valve <NUM> back to the manufacturer for assessment.

Identifier <NUM> can be in an optically readable form. In some embodiments, the optical identifier <NUM> can take a host of different configurations. Identifier <NUM> can be a one-dimensional (1D) code (e.g., a barcode or dotcode, etc.), a two-dimensional (2D) code (e.g., a data matrix code, a Quick Response (QR) code, an Aztec code, etc.), a three-dimensional (3D) code (e.g., a colored 2D code, etc.), or any combination thereof. Identifier <NUM> can alternatively be a sequence or array of recognizable characters, such as alphanumeric characters and/or symbols. The information coded in identifier <NUM> can be recognized by scanning equipment <NUM>, which may be in the form of an optical character recognition (OCR) or equivalent software or hardware (see, e.g., <FIG>). Identifier <NUM> can also include two or more of the aforementioned media in combination (e.g., a 2D code with OCR text).

The embodiments of identifier <NUM> described herein are not limited to optically readable identifiers, and other types of identifiers can be used. For example, in certain embodiments, identifier <NUM> may be one that is 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), and so forth. These other forms or frequencies of identifiers can be used alone or in combination with optically readable forms described above.

While not limited to such, example embodiments will now be described where identifier <NUM> is placed on the surface of frame <NUM> prior to leaflet formation. In this embodiment, identifier <NUM> contains information that defines valve <NUM>'s type (such as aortic or mitral), size (e.g., <NUM> to <NUM> in increments of <NUM> for Aortic, and <NUM> to <NUM> in increments of <NUM> for Mitral), and a valve-specific identifier (e.g., a unique serial number) that can be tracked throughout the entire manufacturing process.

<FIG> is a block diagram depicting an example manufacturing environment <NUM>, including reader device <NUM>, computer system <NUM>, and manufacturing equipment <NUM>, each of which is communicatively coupled to the others. Reader device <NUM> is configured to read identifier <NUM> from valve frame <NUM> (in a state with or without leaflets). Reader device <NUM> includes processing circuitry <NUM> and non-transitory memory <NUM> that stores software instructions that, when executed by processing circuitry <NUM>, cause reader device <NUM> to read identifier <NUM>. The software instructions can also cause processing circuitry <NUM> to transfer the read information from identifier <NUM> to another system, such as computer system <NUM> and/or manufacturing equipment <NUM>, where the information can be further utilized in manufacturing.

Non-transitory memory <NUM> of computer system <NUM> includes software instructions that, when executed by processing circuitry <NUM>, cause processing circuitry <NUM> to read the information communicated from reader device <NUM>. The instructions can further cause processing circuitry <NUM> to transfer relevant portions of the information to manufacturing equipment <NUM> for further use in manufacturing. The instructions can also or alternatively cause processing circuitry <NUM> to select an appropriate software program, function, or parameter for use in manufacturing valve <NUM> and either execute that program, function, or parameter, or transfer it to manufacturing equipment <NUM> for execution.

Manufacturing equipment <NUM> can include processing circuitry <NUM> and non-transitory memory <NUM>. Non-transitory memory <NUM> includes software instructions that, when executed by processing circuitry <NUM>, cause processing circuitry <NUM> to read the information communicated from either reader device <NUM> or computer system <NUM>. The instructions can further cause processing circuitry <NUM> to select an appropriate software program, function, or parameter for use in manufacturing valve <NUM> and execute that program, function, or parameter. Manufacturing equipment <NUM> can be, for example, control equipment <NUM>, <NUM>, <NUM>, and/or <NUM> and the software program, function, or parameter can be for control of chambers <NUM>, <NUM>, <NUM>, and/or facility <NUM>. Manufacturing equipment <NUM> can be, for example, automated transfer equipment <NUM> and the software program, function, or parameter can be for control of equipment <NUM> in moving valve <NUM>. Manufacturing equipment <NUM> can be, for example, cutting system <NUM> and the software program, function, or parameter can be for control of cutting system <NUM> in EHC <NUM>. Manufacturing equipment <NUM> can be, for example, equipment used in finishing valve <NUM> (e.g., trimming, sewing a cuff, measuring, inspecting, packaging) and the software program, function, or parameter can be for control of the finishing equipment.

<FIG> is a flow diagram depicting an example embodiment of a method <NUM> of utilizing identifier <NUM> during one or more manufacturing processes. At <NUM>, an identifier <NUM> is applied to a frame <NUM>. At <NUM>, identifier <NUM> can be read or scanned with a reader device <NUM>, and the read information can be automatically communicated by reader device <NUM> to computer system <NUM>. In some cases, frame <NUM> can be coated, and reading identifier <NUM> can occur through the coating. At <NUM>, computer system <NUM> can process the information received from reader device <NUM> and output the information to manufacturing equipment <NUM> (e.g., facility <NUM>, chambers <NUM>-<NUM>, automated equipment <NUM>, etc.). Then, at <NUM>, manufacturing equipment <NUM> can select a software program or function (or other parameters) for performing an operation or action on valve <NUM> based on the received information. In other embodiments, computer system <NUM> can select the appropriate software program, function, or parameters and output them directly to manufacturing equipment <NUM>. For example, computer system <NUM> can instruct particular equipment <NUM> to execute a particular program.

The operation or action selected at <NUM> to be performed on valve <NUM> can be a step in manufacturing valve <NUM> (e.g., coating frame <NUM> at step <NUM>, dipping step <NUM>, first phase curing step <NUM>, second phase curing step <NUM>, or a finishing step <NUM> (e.g., trimming, attaching a sewing cuff, visual inspection, packaging). For example, equipment associated with the valve dipping <NUM> can receive, from computer system <NUM>, the valve <NUM>'s type and size to select a processing software program that ensures that the valve is dipped to the correct depth, at the correct speed, and remains dipped for the proper time, while exposed to the proper environmental conditions. Equipment associated with EHC <NUM> can receive, from computer system <NUM>, the valve <NUM>'s type and size to select a processing software program that ensures that the valve is rotated at the correct speed, for the proper time, while exposed to the proper environmental conditions. Equipment associated with chamber <NUM> can receive, from computer system <NUM>, the valve <NUM>'s type and size to select a processing software program that ensures that the valve is cured under the proper environmental conditions for the proper time. Equipment associated with valve trimming can receive, from computer system <NUM>, the valve <NUM>'s size and type to ensure the correct program is executed to cut leaflets <NUM> (and mandrel <NUM>) at the correct position. Equipment associated with a cuff sewing system can receive, from computer system <NUM>, the valve <NUM>'s size and type to ensure the correct program is executed to suture the sewing cuff onto the finished valve prosthesis <NUM>.

The operation or action can also be a step of moving valve <NUM> from one location to another, e.g., moving valve <NUM> from EHC <NUM> to chamber <NUM> with automated transfer equipment <NUM>. This information can inform transfer equipment <NUM> of the precise location of valve <NUM> (as valves vary in size). The operation or action can also be a step of measuring valve <NUM> to ascertain a leaflet measurement (e.g., thickness).

For example, in some embodiments, prior to or upon entering a particular stage of manufacturing, valve <NUM> can be scanned either automatically or by a person using an automatic scanner <NUM> in step <NUM>. This information can be relayed to the computer system <NUM> in step <NUM>, which can then output that information or a portion thereof to the automated manufacturing equipment of the particular stage of manufacturing. The information passed to the manufacturing equipment can include additional information that is not coded by the identifier <NUM>, such as a log file with in-line size measurements, or other measured or recorded variables that describe the condition of the valve <NUM> or the manner in which it has been processed thus far. The manufacturing equipment can utilize this information to set appropriate processing parameters for processing the valve <NUM> at a particular manufacturing stage.

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

Upon exiting a given manufacturing stage, valve <NUM> can be scanned again so as to track valve <NUM>'s location and time of exit. Then, upon reaching the next stage, valve <NUM> can be scanned again. This process can repeat for each stage of manufacturing. This can occur one or more times depending on the number of stages of manufacturing used to fabricate valve <NUM>, or the number of stages of manufacturing in which specific valve identity is desired to be utilized. Valve <NUM> does not need to be scanned at every stage, for example, in those stages where a linear processing line exists such that the manufacturing equipment knows with certainty the identify of each valve <NUM>.

For example, in some embodiments, valve <NUM> can be scanned upon entering a measuring stage. A Digital Measuring System (DMS) can receive, from computer system <NUM>, the valve <NUM>'s type, size and/or serial number to ensure that both the correct measurement program can be selected for that particular valve <NUM> by the DMS and that the data is either treated as a master measurement for that valve <NUM> (e.g., a measurement prior to dipping <NUM> and leaflet formation) or a thickness measurement (e.g., a measurement after curing <NUM>) where the thickness of leaflets <NUM> can be ascertained.

Throughout the entire manufacturing process, the output data as well as the date and time of every operation is continuously recorded on a digital structured query language (SQL) server to create and update valve <NUM>'s log file (e.g., digital design history record).

The embodiments of valve <NUM> described herein are suitable for implantation in the body of a patient using any number of medical procedures. Preferably, these embodiments of valve <NUM> are for direct implantation into the body using open heart surgery. Such embodiments of valve <NUM> are not radially collapsible for insertion into an intravascular delivery device (e.g., a catheter) or a transapical delivery device. However, in other embodiments, valve <NUM> can be configured with a radially collapsible support structure <NUM> that allows the lateral dimension of valve <NUM> to be reduced by a degree sufficient to permit the insertion into an appropriately sized intravascular or transapical delivery device.

Example embodiments of systems, devices, and methods are described herein that relate to the manufacture of prosthetic heart valves. However, the scope of the present disclosure is not limited to such, and can likewise be applied to prosthetics for replacement of other valves in other locations in the patient's body outside of the heart.

In all the embodiments described herein, automated steps are performed by processing circuitry executing software instructions. The software instructions can be stored in non-transitory memory. The processing circuitry and non-transitory 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 accessing remotely stored information across a network. The processing circuitry can be a microprocessor, array of processors, programmable logic controller (PLC), circuitry distributed across multiple different devices, or others. The non-transitory memory can be volatile or nonvolatile memory, can be integrated on the same chip as the processing circuitry, a different chip, distributed across multiple chips, or others.

The embodiments described herein are restated and expanded upon in the following paragraphs without explicit reference to the figures. In many example embodiments, a method of valve leaflet manufacture is provided, including: applying polymer in a liquid state to a valve frame and a leaflet formation structure; loading the valve frame and the leaflet formation structure, with the polymer in the liquid state, into a chamber; and automatically moving the valve frame and the leaflet formation structure around the chamber for a period of time during which the polymer at least partially cures.

In some embodiments, applying polymer in a liquid state to the valve frame and the leaflet formation structure includes: dip-coating the valve frame by submerging at least a portion of the valve frame and the leaflet formation structure in a reservoir filled with the polymer in the liquid state; and removing the at least the portion of the valve frame and the leaflet formation structure from the reservoir.

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

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

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.

In some embodiments, automatically moving the valve frame and the leaflet formation structure around the chamber includes moving the valve frame and the leaflet formation structure through at least <NUM>% of a cross sectional area of the chamber.

In some embodiments, no gas is fan-driven within the chamber during the period of time.

In some embodiments, the method further includes removing the valve frame and the leaflet formation structure from the chamber.

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

In some embodiments, when the chamber is closed, and the valve frame is automatically moved around the chamber, the humidity in the chamber is controlled to ± <NUM>%.

In some embodiments, the chamber has a volume of <NUM>,<NUM> cubic cm (<NUM> cubic inches) or less.

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

In some embodiments, the chamber is a first chamber, and the method further includes: removing the valve frame and the leaflet formation structure from the first chamber after the period of time, where the polymer is only partially cured; inserting the valve frame and the leaflet formation structure into a second chamber; and heating the valve frame and the leaflet formation structure in the second chamber until the polymer cures. The method can further include trimming 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 between <NUM> and <NUM> microns in thickness.

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 polymer in the liquid state to a second valve frame and a second leaflet formation structure; loading the second valve frame and the second leaflet formation structure, with the polymer in the liquid state, into the chamber; 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 the 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 cures. The method can further include: removing the second valve frame and the second leaflet formation structure from the first chamber after the period of time, where the polymer is only partially cured; inserting the second valve frame and the second leaflet formation structure into the second chamber; heating the second valve frame and the second leaflet formation structure in the second chamber until the polymer cures; and trimming cured polymer to form a plurality of leaflets on the second valve frame. A variation in thickness 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 <NUM> microns in thickness.

In many embodiments, a method of valve leaflet manufacture is provided, the method including: applying polymer in a liquid state to a valve frame and a leaflet formation structure; loading the valve frame and the leaflet formation structure, with the polymer in the liquid state, into a first chamber and partially curing the polymer while the valve frame and the leaflet formation structure are within the first chamber; and loading the valve frame and the leaflet formation structure, with the polymer in a partially cured state, into a second chamber and curing the polymer while the valve frame and the leaflet formation structure are within the second chamber.

In some embodiments, the method further includes automatically moving the valve frame and the leaflet formation structure around the first chamber for a period of time during which the polymer partially cures. Automatically moving the valve frame and the leaflet formation structure around the first chamber can further include moving the valve frame and the leaflet formation structure through at least <NUM>% of a cross sectional area of the chamber.

In some embodiments, the method further includes automatically rotating the valve frame and the leaflet formation structure around the first chamber in a plane perpendicular to an axis for a period of time during which the polymer partially cures. The valve frame and the leaflet formation structure can be rotated at least one full rotation about the axis. Automatically rotating the valve frame and the leaflet formation structure around the first chamber can include moving the valve frame and the leaflet formation structure through at least <NUM>% of a cross sectional area of the chamber.

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

In some embodiments, no gas is fan-driven within the first chamber for a period of time during which the polymer partially cures.

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 formation structure into the second chamber.

In some embodiments, when the first chamber and the polymer is partially curing, the humidity in the chamber is controlled to ± <NUM>%.

In some embodiments, the method further includes the first chamber has a volume of <NUM>,<NUM> cubic cm (<NUM> cubic inches) or less.

In some embodiments, the method further includes trimming cured polymer to form a plurality of leaflets on the valve frame.

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 polymer in a liquid state to a second valve frame and a second leaflet formation structure; loading the second valve frame and the second leaflet formation structure, with the polymer in the liquid state, into the first chamber and partially curing the polymer while the first valve frame, the first leaflet formation structure, the second valve frame, and the second leaflet formation structure are within the first chamber; and loading the second valve frame and the second leaflet formation 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 formation structure, the second valve frame, and the second leaflet formation structure are within the second chamber. The method can further include trimming cured polymer to form a plurality of leaflets on the second valve frame. The variation in thickness 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 <NUM> microns in thickness. The method can include removing the valve frame and leaflet formation structure from the second chamber. After removal from the second chamber the polymer on the leaflet formation structure can be between <NUM> and <NUM> microns in thickness.

In many embodiments, an apparatus for partial curing of polymer is provided, the apparatus including: a chamber; a movable fixture in the chamber, the movable fixture including at least one receptacle; a motor coupled with the movable fixture and configured to cause the fixture to move; a humidity sensor in the chamber; a first controllable output in the chamber, the first controllable output configured to controllably dispense a first medium into the chamber; 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; and a control system communicatively coupled with the humidity sensor and the first and second controllable outputs, the control system programmed to control humidity within the chamber.

In some embodiments, the receptacle is configured to hold a valve frame or a leaflet formation structure.

In some embodiments, the movable fixture includes a plurality of receptacles, each being configured to hold a valve frame or a leaflet formation structure.

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

In some embodiments, the movable fixture is configured to rotate, and the motor is a rotation motor.

In some embodiments, the movable fixture is adapted to move the receptacle through at least <NUM>% of a cross sectional area of the chamber.

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

In some embodiments, the control system is programmed to control humidity within the chamber to within ± <NUM>% of a humidity setting.

In some embodiments, the chamber includes a door. The door can be pneumatically actuatable.

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

In some embodiments, reading the identifier includes reading information coded in the identifier by scanning equipment; and automatically communicating the information from the scanning equipment to a computer system over a communicative coupling. The scanning equipment can include processing circuitry and non-transitory memory on which a plurality of instructions are stored that, when executed by the processing circuitry, cause the processing circuitry to cause communication of the information from the scanning equipment to the computer system. The method can further include: processing, by the computer system, the information received from the scanning equipment and outputting corresponding information to manufacturing equipment. The method can further include: automatically selecting, by the manufacturing equipment, a software program, function, or parameter for performing an operation or act on the prosthetic valve based on the corresponding information. The computer system can include processing circuitry and non-transitory memory on which a plurality of instructions are stored that, when executed by the processing circuitry, cause the processing circuitry to process the information received from the scanning equipment and output corresponding information to the manufacturing equipment. The manufacturing equipment can include processing circuitry and non-transitory memory on which a plurality of instructions are stored that, when executed by the processing circuitry, cause the processing circuitry to automatically select a software program for performing a manufacturing operation on the valve based on the corresponding information.

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

In some embodiments, the identifier is a QR code.

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 aortic or mitral. The valve size can be one of: <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM>.

In some embodiments, the method further includes: automatically selecting a software program, function, or parameter for an automated operation or act to be performed on the valve prosthesis based on information read from the identifier. The software program, function, or parameter can be for applying a polymer to the coated valve frame and a leaflet formation structure, where the polymer is for formation of 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 a polymer on the valve frame and on a leaflet formation structure. The software program, function, or parameter can be for an automated second phase of curing a polymer on the valve frame and on a leaflet formation structure. The software program, function, or parameter can be for trimming a cured polymer to form 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 transferring the valve frame between manufacturing stages. The software program, function, or parameter can be for finishing the valve frame.

In many embodiments, a prosthetic valve is provided that includes: a frame having an identifier thereon, the identifier being machine readable; and a plurality of polymeric leaflets integrally coupled with 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.

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

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

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

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

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

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

In some embodiments, the frame and the identifier are covered by a coating and the layer of polymer over the coating, where the identifier remains machine readable through both the coating and the layer of polymer.

In some embodiments, the identifier is readable with radio frequency (RF) energy.

In some embodiments, the prosthetic valve is a prosthetic heart valve. The identifier can represent at least a type of the prosthetic heart valve. The type of the prosthetic heart valve can be either aortic or mitral.

Various aspects of the present subject matter are set forth below, in review of, and/or in supplementation to, the embodiments described thus far, with the emphasis here being on the interrelation and interchangeability of the following embodiments. In other words, an emphasis is on the fact that each feature of the embodiments can be combined with each and every other feature unless explicitly stated otherwise or logically implausible.

Those of ordinary skill in the art will readily recognize, in light of this description, the many variations of suitable dip casting procedures, pressures, and temperatures that are not stated here yet are suitable to fabricate the prosthetic heart valves described herein. Likewise, those of ordinary skill in the art will also recognize, in light of this description, the alternatives to dip casting that can be used to fabricate the prosthetic heart valves described herein.

As used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

Where a range of values is provided, each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the disclosure and can be claimed as a sole 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 limits are also included in the disclosure.

Where a discrete value or range of values is provided, that value or range of values may be claimed more broadly than as a discrete number or range of numbers, unless indicated otherwise. For example, each value or range of values provided herein may be claimed as an approximation and this paragraph serves as antecedent basis and written support for the introduction of claims, at any time, that recite each such value or range of values as "approximately" that value, "approximately" that range of values, "about" that value, and/or "about" that range of values. Conversely, if a value or range of values is stated as an approximation or generalization, e.g., approximately X or about X, then that value or range of values can be claimed discretely without using such a broadening term.

Claim 1:
A method of valve leaflet (<NUM>) manufacture, comprising:
applying polymer in a liquid state to a valve frame (<NUM>) and a leaflet formation structure (<NUM>) by dip-coating the valve frame (<NUM>) by submerging at least a portion of the valve frame (<NUM>) and the leaflet formation structure (<NUM>) in a reservoir filled with the polymer in the liquid state;
loading the valve frame (<NUM>) and the leaflet formation structure (<NUM>), with the polymer in the liquid state, into a first environmental humidity chamber (<NUM>) having a humidity sensor (<NUM>) and control equipment (<NUM>) to maintain a controlled humidity environment greater than <NUM>% and less than <NUM>%;
automatically moving the valve frame (<NUM>) and the leaflet formation structure (<NUM>) around the environmental humidity chamber (<NUM>) for a period of time during which the humidity within the environmental humidity chamber (<NUM>) is controlled and during which the polymer at least partially cures; the method further comprising:
removing the valve frame (<NUM>) and the leaflet formation structure (<NUM>) from the first environmental humidity chamber (<NUM>) after the period of time, wherein the polymer is only partially cured;
inserting the valve frame (<NUM>) and the leaflet formation structure (<NUM>) into a second environmental humidity chamber (<NUM>); and
heating the valve frame (<NUM>) and the leaflet formation structure (<NUM>) in the second environmental humidity chamber (<NUM>) until the polymer cures.