Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R21EB030654. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S. Alaie and J. Mata also thank the Department of Mechanical and Aerospace Engineering and the College of Engineering at New Mexico State University for their support. The authors&#160;thank Oscar Lara and Angel de Jesus Zuniga Ramirez for their contributions in generating Figure 2 and editing the references.&#160;The authors also thank Andrea Gonzalez Martinez and Jesus Armando Gil Parra for their contributions to the video demonstrations.

NOTE: See the Table of Materials for details related to all materials used in this protocol. Figure 1A shows an example of the copper/NiTi frame. Use safety gloves.
1. Iteration of a design of a NiTi frame/prototype
<ol>
	<li>Align NiTi wire inside copper tubes (or brass tubes; Figure 2A).
	<ol>
		<li>Select NiTi wire (0.008 in) and a copper tube (OD 1.00 mm x 400 mm).</li>
		<li>Turn on the stereos...

Cost-Effective Shape Setting of NiTi Wires Using Sacrificial Copper Fixtures

<ol>
	<li>Smith, S., Hodgson, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Shape+setting+nitinol.">Shape setting nitinol.</a> Proc of the Mater Process Med Devices Conf. , 266-270 (2004).</li><li>Kapoor, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nitinol+for+medical+applications:+A+brief+introduction+to+the+properties+and+processing+of+nickel+titanium+shape+memory+alloys+and+their+use+in+stents.">Nitinol for medical applications: A brief introduction to the properties and processing of nickel titanium shape memory alloys and their use in stents.</a> Johnson Matthey Tech Rev. 61 (1), 66-76 (2017).</li><li>Viscuso, S., Gualandris, S., De Ceglia, G., Visentin, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Shape+memory+alloys+for+space+applications.">Shape memory alloys for space applications.</a> Shape Mem Alloy Eng. , 609-623 (2021).</li><li>Liu, X., Wang, Y., Yang, D., Qi, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+ageing+treatment+on+shape-setting+and+superelasticity+of+a+nitinol+stent.">The effect of ageing treatment on shape-setting and superelasticity of a nitinol stent.</a> Mater Charact. 59 (4), 402-406 (2008).</li><li>Dulal, H., Swan, T., Al'aref, S. J., Alaie, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-cost+prototyping+of+nitinol+wires/frames+using+polymeric+cores+and+sacrificial+fixtures+with+application+in+individualized+frames+anchoring+through+the+atrial+septum.">Low-cost prototyping of nitinol wires/frames using polymeric cores and sacrificial fixtures with application in individualized frames anchoring through the atrial septum.</a> Sci Rep. 13, 21853 (2023).</li><li>Alaie, S., Robinson, S. S., Amiri Moghadam, A. A., Auge, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advanced+manufacturing+of+patient+specific+occluders+for+the+left+atrial+appendage+with+minimally+invasive+delivery.">Advanced manufacturing of patient specific occluders for the left atrial appendage with minimally invasive delivery.</a> Adv Eng Mate. 22, 1901074 (2020).</li><li>Robinson, S. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-specific+design+of+a+soft+occluder+for+the+left+atrial+appendage.">Patient-specific design of a soft occluder for the left atrial appendage.</a> Nat Biomed Eng. 2, 8-16 (2018).</li><li>Amiri Moghadam, A. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toward+development+of+inflatable+stents+with+application+in+endovascular+treatments.">Toward development of inflatable stents with application in endovascular treatments.</a> Adv Funct Mater. 28 (51), 9 (2018).</li><li>Chen, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Design, parameter optimization and in vitro evaluation of implantable medical devices. , (2018).</li><li>Bernini, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oversizing+of+self-expanding+nitinol+vascular+stents-a+biomechanical+investigation+in+the+superficial+femoral+artery.">Oversizing of self-expanding nitinol vascular stents-a biomechanical investigation in the superficial femoral artery.</a> Journal of the Mechanical Behavior of Biomedical Materials. 132, 105259 (2022).</li><li>Bernini, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surface+finishing+of+n+itinol+for+implantable+medical+devices:+A+review.">Surface finishing of n itinol for implantable medical devices: A review.</a> J Biomed Mater Res Part B Appl Biomater. 110 (12), 2763-2778 (2022).</li><li>Funk, K. A., Hampshire, V. A., Schuh, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nonclinical+safety+evaluation+of+medical+devices.">Nonclinical safety evaluation of medical devices.</a> Toxicol Pathol. , 95-152 (2018).</li><li>. Non-clinical engineering tests and recommended labeling for intravascular stents and associated delivery systems - Guidance for industry and FDA staff Available from: <a target="_blank" href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/non-clinical-engineering-tests-and-recommended-labeling-intravascular-stents-and-associated-delivery">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/non-clinical-engineering-tests-and-recommended-labeling-intravascular-stents-and-associated-delivery</a> (2018)</li><li>Rokicki, R., Hryniewicz, T., Pulletikurthi, C., Rokosz, K., Munroe, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Towards+a+better+corrosion+resistance+and+biocompatibility+improvement+of+nitinol+medical+devices.">Towards a better corrosion resistance and biocompatibility improvement of nitinol medical devices.</a> J Mat Eng Perform. 24, 1634-1640 (2015).</li><li>Hryniewicz, T., Rokicki, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modification+of+nitinol+biomaterial+for+medical+applications.">Modification of nitinol biomaterial for medical applications.</a> World Scientific News. (96), 35-58 (2018).</li><li>Handa, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemocompatibility+comparison+of+biomedical+grade+polymers+using+rabbit+thrombogenicity+model+for+preparing+nonthrombogenic+nitric+oxide+releasing+surfaces.">Hemocompatibility comparison of biomedical grade polymers using rabbit thrombogenicity model for preparing nonthrombogenic nitric oxide releasing surfaces.</a> J Mater Chem B. 2 (8), 1059-1067 (2014).</li><li>Li, P., Wang, Y., Meng, F., Cao, L., He, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+heat+treatment+temperature+on+martensitic+transformation+and+superelasticity+of+the+Ti49Ni51+shape+memory+alloy.">Effect of heat treatment temperature on martensitic transformation and superelasticity of the Ti49Ni51 shape memory alloy.</a> Materials. 12 (19), 2539 (2019).</li><li>Duerig, T., Pelton, A., St&#246;ckel, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+overview+of+nitinol+medical+applications.">An overview of nitinol medical applications.</a> Mat Sci and Eng: A. 273, 149-160 (1999).</li><li>Kwok, D., Schulz, M., Hu, T., Chu, C., Chu, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surface+treatments+of+nearly+equiatomic+niti+alloy+(nitinol)+for+surgical+implants,+biomedical+engineering.">Surface treatments of nearly equiatomic niti alloy (nitinol) for surgical implants, biomedical engineering.</a> Trends in Mater Sci. , 269-282 (2011).</li><li>Williams, K. R., Gupta, K., Wasilik, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Etch+rates+for+micromachining+processing-part+ii.">Etch rates for micromachining processing-part ii.</a> II. J of Microelectromech Syst. 12 (6), 761-778 (2003).</li><li>Yip, M. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-cost+and+rapid+shaping+of+nitinol+for+medical+device+prototyping.">Low-cost and rapid shaping of nitinol for medical device prototyping.</a> ASME Open J of Eng. 2, 021027 (2023).</li></ol>

In this protocol, multiple steps require meticulous attention such as the heat treatment (annealing), etching, and design of 3D-printed fixtures. Large variations in temperature from 500 &#176;C 17 or the annealing time of NiTi can be detrimental to the superelasticity of the NiTi wire and to achieving the desired shapes18. Heat treatment with inaccurate conditions (temperature and time) can also lead to a loss of the superelastic property19. The etc...

NiTi wires are widely used in medical implants but require an initial shape-setting process during device fabrication1. Various devices are made from NiTi, including catheter tubes, guidewires, stone retrieval baskets, filters, needles, dental files, as well as other surgical instruments2. NiTi&#39;s biocompatibility, superelasticity, and fatigue resistance make it suitable for these applications. Additionally, it has applications in the automotive and aerospace industries3.
Despite the broad applications of NiTi, its usage is limited due to its high cost and complex processes needed for shape-setting. In the shape-setting process, NiTi structures are traditionally exposed to high temperatures (about 500 &#176;C) while confined in a fixture4. This elevated temperature, as well as the stresses during the shape-setting process, requires a fixture with high mechanical strength. This is why typical fixtures are usually made from metals1. As such, the use of metal fixtures that are typically machined increases costs and poses challenges for the rapid prototyping and testing of NiTi structures. One alternative approach involves the use of reconfigurable fixtures constructed from pins and plates1, which simplifies the process; however, this process has limitations in the shaping of complex geometries. Accordingly, a low-cost, shape-setting process using low-cost materials and manufacturing is highly desirable for research that requires shape-setting NiTi frames.
To address the need for rapid prototyping of NiTi, we recently introduced a protocol utilizing low-cost 3D printed parts and crafted manufacturing for shape-setting NiTi wires5. This method incorporates sacrificial fixtures with a minimal mass. The fixture is shown to be beneficial in securing the NiTi wire during wire forming and shape-setting (heat treatment) processes. Copper tubes were employed as an accessible and low-cost material. It acts as a reinforcing sacrificial fixture and the standard wire bending techniques can be used for shape-setting complex structures. It was observed that the brass tubes could be used as an alternative. Ammonium persulfate was utilized in the final stage for the selective etching of copper, after the annealing process. This step finally released the shape-set NiTi wires. This approach illustrates the innovative use of sacrificial structures as spacers. When this approach is combined with additive manufacturing, the fabrication of complex shapes can be achieved.
In vitro deployment test is among the basic tests for assessing the feasibility of a self-expending prototype implant, designed to be deployed through a catheter. These tests involve assessing if a self-expanding implant can successfully pass through a sheath/catheter with the required dimension. Such tests have been used in various transcatheter devices or implant prototypes; some examples include left atrial appendage occluders6,7, soft-stents8, NiTi flow diverter9, and NiTi stents10. These works highlight the need for a methodology for rapidly fabricating NiTi frames with complex topologies, which could self-expand through catheters thereby satisfying the preliminary requirements for a transcatheter implant.
The aim of this paper is to outline cost-efficient and well-crafted manufacturing methods, providing a detailed, step-by-step guide through each process. It focuses on demonstrating a variety of self-expanding NiTi wire frames suitable for implants and analyzes key aspects of the method needed to produce complex topologies using affordable and efficient techniques. This&#160;paper includes testing these frames and deploying them through a Fr-12 catheter in a benchtop setup that simulates transeptal implant delivery to the atrial septum. This test is similar to basic tests, employed by prior work6,8. This method demonstrated the capability of deployment of a prototype self-expanding frame after passing through a catheter. Ultimately, this methodology can help determine if a certain topology/design for a NiTi frame can meet the preliminary mechanical requirements for deployment through a specific catheter.
While this work&#160;focuses on the fabrication of prototypes for NiTi frames and the basic characterization of their topology and conformality, various other characterizations11 and regulatory safety tests12,13 are necessary for the development of implants. Some characterizations include characterization of surface properties/chemistry14, corrosion14, fatigue analysis13, hemocompatibility13, and biocompatibility15.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>304 SS Hypotubes 
			Generic Name: Needle</td>
			<td>Tegra Medical</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>3D printed frame for testing 
			Generic Name: PLA filament</td>
			<td>R3D</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>3D printed polymeric part for heat press 
			Generic Name: PLA filament</td>
			<td>R3D&#160;</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ammonium Persulfate 
			Generic Name: Ammonium Persulfate</td>
			<td>Sigma-Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Chronoflex AR 22% 
			Generic Name: Polyurethane</td>
			<td>AdvanSource biomaterials</td>
			<td></td>
			<td>aromatic polycarbonate urethane elastomer&#160;</td>
		</tr>
		<tr>
			<td>Copper Web Type Electrodes (1.00 mm x 400 mm) 
			Generic Name: Copper Tube</td>
			<td>Holepop edm supplies &#38;electrodes</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dilator 
			Generic Name: Dilator</td>
			<td>QOSINA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ecoflex 00-30 
			Generic Name: Ecoflex 00-30</td>
			<td>Smooth-on</td>
			<td></td>
			<td>silicone</td>
		</tr>
		<tr>
			<td>Fr 12 or 13 Catheter 
			Generic Name: Sheath</td>
			<td>QOSINA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Nickel Titanium Wire (0.008) 
			Generic Name: NiTi Wire</td>
			<td>Malin Co.&#160;</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PTFE Teflon rod 1/8&#34; Diameter x 36&#34; 
			Generic Name: Polytetrafluoroethylene&#160;</td>
			<td>Sterling Seal &#38; Supply, Inc. (STCC)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Tecoflex 
			Generic Name: Thermoplastic Polyurethane</td>
			<td>Lubrizol</td>
			<td></td>
			<td>aliphatic polyurethane elastomer&#160;</td>
		</tr>
		<tr>
			<td>Trichloro(1H,1H,2H,2H-tridecafluoro-n-octyl)silane 
			Generic Name: C8H4Cl3F13Si</td>
			<td>Sigma-Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dimethylacetamide (DMAC) 
			Generic Name: Dimethylacetamide</td>
			<td>Sigma-Aldrich</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>SOLIDWORKS 
			Generic Name: Proprietary CAD software</td>
			<td>Dassault Syst&#232;mes</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>FreeCAD 
			Generic Name: Open Source CAD software</td>
			<td>freecad.org</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>ABS Like Photopolymer Resin 
			Generic Name: Photopolymer Resin</td>
			<td>ELEGOO</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

rapid formation and testing of self-expanding niti frames with a small form factor suitable for minimally invasive implants

NiTiNOL (commonly referred to as nitinol or NiTi) wires feature exceptional shape memory and super-elastic characteristics, while shape-setting is often a costly process. Among the steps for this process, heat treatment requires exposure to high temperatures for shape-setting. Traditionally, metal fixtures are used for this purpose; however, their manufacturing costs can be significant, which is not ideal for iterating prototypes. This work demonstrates a recently introduced approach using sacrificial fixtures made of copper tubes, which eliminates the need for expensive fixtures. These copper tubes allow for the formation of complex geometries, and they offer a scaffold for various phases of the fabrication process. Moreover, ammonium persulfate is used as the agent for selective copper etching, which simplifies the production of NiTi frames. This work&#39;s findings confirm the effectiveness of this technique, as demonstrated in the successful shape-setting of NiTi wires for self-expanding frames. This methodology paves the way for future research, allowing for rapid prototyping of NiTi wireframes for various applications especially those in medical devices.

Author Spotlight: Rapid Prototyping and Testing of Self-Expanding Nitinol Frames for Transcatheter Implantable Devices

Rapid Formation and Testing of Self-expanding NiTi Frames with a Small Form Factor Suitable for Minimally Invasive Implants

NiTi frames were shape-set into various topologies using low-cost plastic fixtures and hand tools (Figure 1). In protocol steps 1.1 to 1.4 (Figure 1A), NiTi/Cu frames were formed into complex topologies. Following protocol step 1.5, Cu was etched to release the NiTi frames (Figure 1B). Here, the Cu fixture was completely etched away, allowing the NiTi frame to be released using low-cost jigs/fixtures that were 3D printed (step 1.2)....

This work illustrates a low-cost fabrication technique for shape-setting nitinol wires/frames with a small form factor using sacrificial fixtures. The technique is demonstrated for the fabrication of self-expanding frames designed for minimally invasive implants with complex shapes.

NiTiNOL (commonly referred to as nitinol or NiTi) wires feature exceptional shape memory and super-elastic characteristics, while shape-setting is often a ...

Rapid Formation and Testing of Self-expanding NiTi Frames with a Small Form Factor Suitable for Minimally Invasive Implants

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