The authors thank Sungwon Lim for intellectual contributions to device and mold design as well as Jambu Jambulingam and Rebecca Grossman-Kahn for creating intravaginal silicone probes using this process. This work is supported by the Bill and Melinda Gates Foundation, the Vodafone Americas Foundation, and the FDA (2P50FD003793).

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没有一个作家有关于这篇文章中详述的工作的任何竞争经济利益。

所有上述步骤，仔细模具设计是最关键的成功之路。模具主机应该被创建为一个实心体与外部几何形状应使其在最终的设备。这些几何形状应调整，以考虑任何材料收缩率，由于所选择的弹性体以及3D打印机的分辨率和公差。模具分型线和通孔的螺纹杆和螺钉的位置是依赖于彼此。加的分型线增加线性和旋转度模装置自由的编号。贯通孔和螺纹杆和螺丝作用来限制这些相同自由度。模具必须被设计成使得它限制了所有线性和旋转自由度当完全组装时，同时使除去约束螺纹杆和螺钉被移除时完全固化的弹性体装置。如果该固化的弹性体是合理的弹性变形，分型线可以被定义，例如吨帽子的功能悬彼此略有因为完全固化装置可以推或拉出来的模件。如果包覆模制部件是理想的，模具的设计还必须提供定位功能，在一个完全组装模具约束包覆成型的部件的运动。模具的分型线应仔细选择，以尽量减少模具件所必需的，以产生所希望的弹性体装置的数量。最小化的模片和分型线的数量减少为闪光形成的可能性和减少数量的通孔所需的模具组件在压缩模件。根据我们的经验，一个ABS模具持续约20采用ABS塑料穿出来之前，裂纹，银纹或因挤压应力和加热循环。 一旦模件都使用FDM三维打印机被打印，若干修改，可向模件。在某些情况下，模具件由FDM 3D打印机制作可能有INSUFFICIEnt的分辨率的分型线，以产生完全齐平的表面，从而导致一个小的间隙，从而导致闪光形成以及液体弹性体的泄漏。如果发生这种情况，使用一个薄层RTV硅中的组装模具的分型线可以防止液体弹性体的泄漏通过在模具的分型线。另外，表面平滑可以通过添加额外的材料模片（尺寸过他们），打磨到最终尺寸或治疗的ABS用丙酮，逐渐溶解的塑料来完成。这些方法可以仔细用来微调模具的几何形状在离别的边缘，以减少闪光灯的形成。然而，我们必须溶解模具表面时要小心，因为这样做会降低化学塑料的强度，使其更容易开裂和裂纹。这可以减少模具的寿命，并且还影响模具之间的表面几何形状的一致性。此外，它是难以控制uniformitŸ模具解散，这可能会导致在模具的几何形状稍有变化。这可能会成为一个问题，如果多套模具被用于制造设备。要解决这个问题，高解析度的3D印刷技术，可用于模具生产。利用较高分辨率的模具或丙酮处理过的模具的另一个好处是增加的容易脱模过程中分离从ABS成型机的弹性体装置。可替换地，脱模剂可用于涂覆模腔以帮助脱模。然而，对于所述阴道探针在这个程序演示，脱模剂是特别是由于引入模具释放化学物质进入阴道环境的潜在风险避免。也应注意，以确保所选的模具材料不抑制该弹性体的固化。 在包覆成型部件中的硅氧烷弹性体，如用于阴道内探针1的一个挑战是，附着有机硅和金属是出了名的困难。对于阴道探头的要求之一是允许在材料界面小的差距，如果发生在硅弹性变形。这反映出，以允许在阴道内探针的杯状结构弯曲和伸展像周围的子宫颈的套筒，同时还确保金属和设备的硅氧烷部分之间的水密性的欲望。水密性是必要的，因为清洗设备中的过氧化氢等离子体灭菌人体实验的指导方针。这个要求是通过仔细地施加医用级聚硅氧烷与金属粘结底层与硅氧烷装置主体和金属部件之间的连接处，然后施加室温固化（RTV）的硅的金属 - 弹性体结脱模装置之后得到满足。用来提高金属与硅之间的附着力另外一个方法是设计所有嵌入金属部件与圆形散热。注射后，散热片之间的空间是科幻LLED用液体硅胶，然后在固化过程中固化。这种设计特性允许应力从硅体转移到金属部件，同时减少对金属和硅之间的间隙形成的倾向。 虽然有与使用ABS基频分复用3D打印机 - 即快速的打印速度，成本低，且使用该技术的这些优势，必须仔细地相对于取舍是衡量合同印刷服务大量的相关的许多优点进行。 ABS为基础的3D打印机实现了快速原型和迭代开发方法，而ABS本身是适合成型许多弹性体，因为它通常是化学惰性的14,15。然而，ABS树脂具有的热变形温度约为90-100℃，从而限制了最大工作温度在约70℃16。这意味着更高的固化温度不能使用ABS的模具实现的。一SA的结果，用于阴道内探针的弹性体的固化时间从3分钟增加到175℃至5小时，在70℃下如果需要更高的固化温度下是理想的，可以考虑采用其他的FDM的材料，如聚碳酸酯。使用基于SLA的3D打印使最优秀的模具分辨率可能，并提供了多种选择的树脂材料。然而，在FDM技术的不断进步正在缩小这两种技术之间的分辨率差距。而在建立所述阴道探针中使用的基于FDM的模具有254微米的层的分辨率，更新FDM机可以实现100微米的分辨率和下方。基于SLA的3D打印通常是更昂贵，更密集的时间比基于FDM的3D打印，并在内部要少得多设施具备的SLA设备。这些因素使频分复用3D打印机更适合用在低成本快速迭代开发。事实上，SLA通常是由用于聚氨酯设备的原型开发和小批量运行打印一个模具师傅和铸造模具硅胶周围的模具师傅打造模具聚氨酯注入。使用硅胶作为模具材料的好处是，它是一种热固性聚合物和不会熔化在较高的固化温度。但是，它是困难的或不可能的有机硅模具划分成许多块，以产生复杂的模具，如阴道内探针装置;此外，线路走向为包覆成型可能是同样具有挑战性。其结果是，用这种方法生产的硅树脂模具通常是两件式模具和需要传统LIM设备用于注射聚合物注入模腔。因此，尽管这种方法并不像传统的LIM注射昂贵，原型使用这种方法的总成本仍然是相当昂贵和更密集的时间比所描述的协议使用FDM的3D打印机和弹性体注塑修改后的干燥器。所提出的方法的其他好处包括能够直接运行的能力Y打印件模具没有先创建一个物理模具师傅，还有一个事实，即这种技术不需要投资昂贵的SLA或LIM设备。 该方法使复杂的几何形状和要求，这是如医疗设备领域的一个标志弹性体装置的快速成型。标准或文件的方法来快速迭代弹性体设备的缺乏已导致缓慢​​和医疗器械的昂贵的开发。在这个手稿中描述的方法所固有的灵活性允许在几乎任何几何形状被构建并要满足包覆成型的要求。它可用于快速，廉价地迭代器原型在医疗器械开发过程的早期。这是在资源有限的环境中，如学术实验室或启动环境中的3D打印机是越来越普遍，但LIM设备是罕见特别有用。此外，CAD模型，在这个公关产生的ocess可转移到将来的制造工艺，并且可以被用于促进生产用于LIM传统的金属模具。虽然这项技术被证明为医疗设备开发与阴道探头装置，该协议可以很容易地适用于其他领域和应用中，低成本，小批量，以及弹性体为基础的装置快速迭代开发是理想的。

液体注射成型（LIM）（也称为反应注射成型）经常被用来制造从热固性弹性体的弹性装置，但高工装和设备成本需要大量的前期资本投资1。此外，LIM可以在技术上具有挑战性的和昂贵的实现与复杂的几何形状和包覆成型要求的情况。其结果是，它通常是不切实际的，使用传统的LIM在超低量或与早期设备的设计，往往招致迭代修改。 典型的流程型注塑弹性体材料包括注射液单体在大约150磅的压力注入模具使用专门的成型机械2。的温度和压力进行控制，以确保层流，并防止空气被截留在模具3。原料通常是由两部分组成的硫化体系，如铂固化有机硅，叔帽子是在注射之前保存在单独的温度和控制室。原材料的两个组件被泵入高压混合室，其随后送入模腔。固化是通过在催化剂的存在下以及温度约150-200℃4来实现。模具加工通常由钢或铝，公差精确到周围建立离别边缘3,5良好的密封。不幸的是，这个过程一般比较适合于较大规模的生产给予了高度的模具加工成本以及专门的注入和反馈控制系统的要求。 对于聚氨酯（PU）份的快速原型设计，它有可能使用立体光刻（SLA）来创建一个主模和生产硅橡胶模具6,7。然而，这种技术不适合于包覆成型，因为它是难以实现的包覆成型的部件的精确对准，因为硅酮是，由设计，而不是一个刚性结构。此外，生产具有复杂几何形状，如内陷或挖空部分的设备，是困难或不可能。对于复杂或精密模具分型线和刚性薄元素的要求是，往往不是，用液体橡胶成型工艺不兼容。 上述生产规模或后期成型过程往往是不切实际的早期医疗设备开发一些设备需要制作了验证性的概念和可行性在人类研究中，这是常有的情况下，在学术实验室和初创公司的环境。替代品的缺乏常常意味着即使是早期发展会产生高昂的成本，需要许多设备开发，限制设备的功能或将开发搁置，而额外的资金募集。这有助于在开发过程中，因为医疗设备重新很大一部分急剧减速<html> QUIRE实现复杂的功能。这也是困难的，因为概念证明型的数据往往是尚未建立，以应付该等设备的昂贵的开发。我们在本实验中最近的一个项目，涉及硅阴道探头的发展，模制电和光学传感器，需要一个杯状尖，以符合指定的宫颈几何遇到了这个障碍。在这篇文章中描述的过程记录我们试图规避这种恶性循环，并迅速达到证明型概念LIM医疗设备。 在图1中所示的技术解构LIM过程分成5个主要的活动:（1）模具的设计和生产，（2）模具组件（3）弹性体混合，（4）弹性体注射剂，和（5）弹性体的固化和脱模。 PG"宽度="600"/&gt; （1A）创建模具使用计算机辅助设计工具，（1B）的3D打印模件，（2）组装使用螺纹杆和螺丝模件，（:。协议，其中涉及图1协议概述概述3）混合液态弹性体和装入注射器中，（4）注入液体弹性体进入模具用改进的干燥器，（5a）中固化所述弹性体在温度可控的烤箱，和（5b）从脱模固化的弹性体装置模件。 模具设计涉及到计算机辅助设计（CAD）软件，从模具分型线的固体块和定义的模具师傅的减法开发一个模具师傅的。模件被创建，然后组装用螺钉，杆，和锁紧螺母定位在模腔中包覆成型的部件。弹性体混入克包括部分相结合的原料和脱气和B以消除潜在的空隙的材料。接着，弹性体注射涉及模腔的压力驱动的填充，随后弹性体固化的温度控制烘箱中，以确保该聚合物链的化学交联。 打破注塑过程分为以下步骤使我们能够放弃传统的LIM设备支持的低成本替代品。例如，而不是机加工的金属模或铸件从模具主人的硅橡胶模具，从在这个手稿中描述的协议建立的模具是从丙烯腈 - 丁二烯 - 苯乙烯（ABS），使用熔融沉积成型（FDM），三维创建塑料打印机8,9。相较于建筑金属模具或模具的SLA，FDM通常是一个更便宜和更快的过程。相当复杂的模具可迅速被印刷在一个内部的三维打印机，或由许多合同三维内印刷的一个廉价地生产提供3G业务。例如，一个复杂的八件3D印刷模具用于铸造的证明阴道探头在有代表性的结果部分， 如图14和图15所示。所有部件该模具可以打印在大约1.5天一个内部的三维打印机。周转时间为更简单的模具可以是几个小时。必要的时候以原形使用FDM的3D打印机打造模具设备的总长度是类似投出的模具硅橡胶，并创建一个聚氨酯原型所需的时间。然而，使用FDM三维打印机创建模具使得不能容易地使用有机硅模具完成几件事情:（1）许多热固性弹性体可用于所提供的三维印刷模具可以容忍所需的固化温度，（2）复杂的几何形状可以使用许多不同的模件和分型线被创建，以及（3）使用刚性模件允许精确和reproduci在模腔中的OM组件竹叶提取对齐。 而不是使用传统的LIM机，它结合了混合，注射，和固化的，有可能用一个实验室混合器，以确保均匀混合，注射用的改性干燥器，和一个标准的温度控制烘箱中进行固化。注射系统使用现成的搁板组件创建并涉及增加了一个正压力供给线到连接到填充有混合的弹性体的注射器从干燥器中。在台式干燥器室加压通常是由腔室中，真空供给线路，和大气之间的三通阀控制。修改后的干燥器以及正压供给线输送到注射器柱塞的背面。这使得能够创建一个40-50 psi的压力差足以用于液体材料注射到模腔中。 这种技术允许我们机生产线CE硅胶阴道探头，模制电和光学传感器来收集证明了概念数据的I期临床试验。硅酮被选中是因为需要对生物惰性以及消毒用多种方法10,11的能力。此外，该装置需要复杂的和非传统的杯形几何的探针，其中传感器位于与子宫颈的接口的前端。在不使用所描述的技术的，这将是一个更加昂贵和漫长的过程，以产生这些设备。相比于传统的LIM过程，使得它的实际采取快速和迭代方法来设计的弹性装置的LIM过程的这种适应降低了成本和设备的需求。

<table><tbody><tr><td>ABS Model Material</td><td>Stratasys</td><td>P430</td><td>Model Material for uPrint Plus SE (Step: Mold Design &amp;amp; Production)</td></tr><tr><td>Soluble Support Material</td><td>Stratasys</td><td>SR-30</td><td>Support Material for uPrint Plus SE (Step: Mold Design &amp;amp; Production)</td></tr><tr><td>Underwater Silicone Sealant, 2.8 Oz Tube, Clear</td><td>McMaster-Carr Supply Company</td><td>7327A21</td><td>Silicone RTV for sealing gaps at mold parting lines (Step: Mold Assembly)</td></tr><tr><td>Tubing, 1/8&quot; ID, 1/4&quot; OD, 1/16&quot; Wall Thickness, Ultra-chemical-resistant Tygon PVC, Clear</td><td>McMaster-Carr Supply Company</td><td>5046K11</td><td>Forms runner/sprue adapter between mold and syringe with elastomer (Step: Elastomer Mixing)</td></tr><tr><td>Coupling, Adapter, Straight, Male Quick-turn (Luer lock) X 1/8&quot; Tube Barb, Nylon</td><td>McMaster-Carr Supply Company</td><td>51525K123</td><td>Connect runner/sprue between mold and syringe with elastomer (Step: Elastomer Mixing)</td></tr><tr><td>Coupling, Adapter, Staight, Female Quick-turn (Luer lock) X 1/8&quot; Tube Barb, Nylon</td><td>McMaster-Carr Supply Company</td><td>51525K213</td><td>Connect runner/sprue between mold and syringe with elastomer (Step: Elastomer Mixing)</td></tr><tr><td>Cap, Female Quick-turn (Luer lock), Nylon</td><td>McMaster-Carr Supply Company</td><td>51525K315</td><td>Cap to prevent silicone from leaking out of mold after injection (Step: Elastomer Mixing)</td></tr><tr><td>Liquid Silicone Rubber (LSR) 30 - 10:1, Implant Grade</td><td>Applied Silicone Corporation</td><td>PN40029</td><td>Substitute with the elastomer of your choice.&amp;nbsp; This is the one used for the intravaginal probe (Step: Elastomer Mixing)</td></tr><tr><td>Syringes (BD), 1 ml Slip-Tip, non-sterile clean, bulk</td><td>Cole-Parmer</td><td>WU-07945-00</td><td>Syringes for transfering elastomer material (Step: Elastomer Mixing)</td></tr><tr><td>Syringes (BD), 1 ml Slip-Tip, non-sterile clean, bulk</td><td>Cole-Parmer</td><td>WU-07945-04</td><td>Syringes for transfering elastomer material (Step: Elastomer Mixing)</td></tr><tr><td>Syringe, 20 ml, Open Bore, Solid Ring Plunger and Grip</td><td>Qosina Corporation</td><td>C1200</td><td>Syringes for transfering elastomer material.&amp;nbsp; Open bore is used for very viscous elastomers. (Step: Elastomer Mixing)</td></tr><tr><td>Needle (BD), Non-sterile Clean with Shields, 18 G x 1.5&quot; Lg., Stainless Steel, BD Bulk</td><td>Cole-Parmer</td><td>WU-07945-76</td><td>Used for removing air column between syringe plunger and elastomer (Step: Elastomer Mixing)</td></tr><tr><td>Plastic Cups, 12 Oz., Clear</td><td>Safeway</td><td>N/A</td><td>Used for mixing silicone in THINKY Mixer (Step: Elastomer Mixing)</td></tr><tr><td>Polyethylene Bag, Open-Top, Flat, 5&quot; Width x 6&quot; Height, 2-MIL Thk.</td><td>McMaster-Carr Supply Company</td><td>1928T68</td><td>Used for mixing silicone in THINKY Mixer (Step: Elastomer Mixing)</td></tr><tr><td>Rubber Band, Latex Free, Orange, Size 64, 3-1/2&quot; L x 1/4&quot; W</td><td>McMaster-Carr Supply Company</td><td>12205T96</td><td>Used for mixing silicone in THINKY Mixer (Step: Elastomer Mixing)</td></tr><tr><td>Parafilm Wrap, 4&quot; W</td><td>Cole-Parmer</td><td>EW-06720-40</td><td>Used for mixing silicone in THINKY Mixer (Step: Elastomer Mixing)</td></tr><tr><td>Syringe Barrels with Stoppers, Luer Lock, Air Operated,&amp;nbsp; 50 ml</td><td>EWD Solutions</td><td>JEN-JG50A-15</td><td>Smaller syringes can be used if less elastomer is required, but make sure it is compatible with Air Operated Syringe Adapter in injection chamber (Step: Elastomer Mixing)</td></tr><tr><td>Sealant Tape, Pipe Thread, 50&#039; Lg x 1/4&quot; W, 0.0028&quot; Thk, 0.5 G/CC Specific Gravity</td><td>McMaster-Carr Supply Company</td><td>4591K11</td><td>Teflon Tape for air-tight seals around at threads (Step: Elastomer Injection)</td></tr><tr><td>Scalpel Blades, Disposable, No. 22</td><td>VWR</td><td>21909-646</td><td>Used for cutting tubing and demolding (Step: Curing &amp;amp; Demolding)</td></tr><tr><td>Kimwipes</td><td>VWR</td><td>21903-005</td><td>&amp;nbsp;(Step: Curing &amp;amp; Demolding)</td></tr><tr><td>2-Propanol, J. T. Baker</td><td>VWR</td><td>JT9334-3</td><td>&amp;nbsp;(Step: Curing &amp;amp; Demolding)</td></tr><tr><td>uPrint Plus SE 3D Printer</td><td>Stratasys</td><td>uPrint Plus SE</td><td>Other 3D printers can be used (Step: Mold Design &amp;amp; Production)</td></tr><tr><td>Screw, Cap, Hex Head,&amp;nbsp; 1/4&quot;-28 , 2-1/2&quot; Lg, 18-8 Stainless Steel</td><td>McMaster-Carr Supply Company</td><td>92198A115</td><td>Screws used with nuts to compress mold (Step: Mold Assembly)</td></tr><tr><td>Nut, Hex, 1/4&quot;-28, 7/16&quot; Wd, 7/32&quot; Height, 18-8 Stainless Steel&amp;nbsp;</td><td>McMaster-Carr Supply Company</td><td>91845A105</td><td>Screws used with nuts to compress mold (Step: Mold Assembly)</td></tr><tr><td>Stud, Fully Threaded, 1/4&quot;-28, 1&quot; Lg, 18-8 Stainless Steel&amp;nbsp;</td><td>McMaster-Carr Supply Company</td><td>95412A567</td><td>Threaded-rods can be cut to desired length and are used with nutes to compress mold (Step: Mold Assembly)</td></tr><tr><td>Planetary Centrifugal Mixer</td><td>THINKY USA Inc.</td><td>ARE-310</td><td>Mixers are strongly recommended for fine mixing and to reduce degassing time, but hand mixing is fine (Step: Elastomer Mixing)</td></tr><tr><td>Laboratory Weigh Scale</td><td>Mettler-Toledo International Inc.</td><td>EL602</td><td>&amp;nbsp;(Step: Elastomer Mixing)</td></tr><tr><td>Desiccant Vacuum Canister, Reusable,&amp;nbsp; 10-3/4&quot; OD</td><td>McMaster-Carr Supply Company</td><td>2204K7</td><td>This desiccator is used for degassing the elastomer (Step: Elastomer Mixing)</td></tr><tr><td>Custom 3D-Printed Mixer-to-Cup Adapter</td><td>N/A</td><td>N/A</td><td>Modeled in Solidworks CAD and 3D printed (Step: Elastomer Mixing)</td></tr><tr><td>Tubing, Smooth Bore, 1/4&quot; ID, 1/2&quot; OD, 1/8&quot; Wall Thickness, High Purity Tygon PVC, Clear</td><td>McMaster-Carr Supply Company</td><td>5624K51</td><td>Tubing outside of Desiccator (Step: Elastomer Injection)</td></tr><tr><td>Tubing, Smooth Bore, 3/8&quot; ID, 5/8&quot; OD, 1/8&quot; Wall Thickness, High Purity Tygon PVC, Clear</td><td>McMaster-Carr Supply Company</td><td>5624K52</td><td>Tubing to adapt to Air/Vacuum Supply (Step: Elastomer Injection)</td></tr><tr><td>Coupling, Reducer, Straight, Vacuum Barb 3/8&quot; Tube ID X Vacuum Barb 1/4&quot; Tube ID, Brass</td><td>McMaster-Carr Supply Company</td><td>44555K188</td><td>Adapt Tubing outside Desiccator to Tubing leading to Air/Vacuum Supply (Step: Elastomer Injection)</td></tr><tr><td>Clamp, Hose &amp;amp; Tube, Worm-Drive, for 7/32&quot; to 5/8&quot; OD tube, 5/16&quot; Wd., 316 SS</td><td>McMaster-Carr Supply Company</td><td>5011T141</td><td>Used on tubing to create Air/Vacuum-tight seal at junctions (Step: Elastomer Injection)</td></tr><tr><td>Clamp, Hose, Smooth-Band Worm-Drive, for 1/2&quot; to 3/4&quot; OD tube, 3/8&quot; Wd., 304 SS</td><td>McMaster-Carr Supply Company</td><td>5574K13</td><td>Used on tubing to create Air/Vacuum-tight seal at junctions (Step: Elastomer Injection)</td></tr><tr><td>Coupling, Tee, Vacuum Barb 1/4&quot; Tube ID, Brass</td><td>McMaster-Carr Supply Company</td><td>44555K138</td><td>Tee Junction between Vacuum, Three-way T-valve on Desiccator, and Three-way L-valve (Step: Elastomer Injection)</td></tr><tr><td>Coupling, Tee, 1/4 NPT Female X Female X Male, Brass</td><td>McMaster-Carr Supply Company</td><td>50785K222</td><td>Tee Junction between Pressure Gauge, Chamber, and Three-way L-valve (Step: Elastomer Injection)</td></tr><tr><td>Valve, Ball, Straight, T-Handle, 1/4 NPT Female X Male, Brass</td><td>McMaster-Carr Supply Company</td><td>4082T42</td><td>Three-way L-valve (Step: Elastomer Injection)</td></tr><tr><td>Coupling, Adapter, Straight, Vacuum Barb 1/4&quot; ID Tube X 1/4 NPT Male, Brass</td><td>McMaster-Carr Supply Company</td><td>44555K132</td><td>Adapter for Three-way L-valve-to-Tubing (Step: Elastomer Injection)</td></tr><tr><td>Saw, Hole, Bimetal. 1-3/8&quot; OD, 1-1/2&quot; Cutting Depth</td><td>McMaster-Carr Supply Company</td><td>4066A25</td><td>Used to cut holes in Desiccator for throughwall fittings (Step: Elastomer Injection)</td></tr><tr><td>Arbor, 9/16&quot; to 1-3/16&quot; Saw, 1/4&quot; Hex</td><td>McMaster-Carr Supply Company</td><td>4066A76</td><td>Used to cut holes in Desiccator for throughwall fittings (Step: Elastomer Injection)</td></tr><tr><td>Arbor Adapter for 1-1/4&quot; Thru 6&quot; Dia Hole Saws</td><td>McMaster-Carr Supply Company</td><td>4066A77</td><td>Used to cut holes in Desiccator for throughwall fittings (Step: Elastomer Injection)</td></tr><tr><td>Coupling, Straight, Through-Wall, 1/2 NPT Female, Polypropylene</td><td>McMaster-Carr Supply Company</td><td>36895K141</td><td>Throughwall fittings leading to Pressure/Vacuum Gauges (Step: Elastomer Injection)</td></tr><tr><td>Coupling, Adapter, Straight, Reducing,&amp;nbsp; Bushing, Hex, 1/2 NPT Male X 1/4 NPT Female, Brass</td><td>McMaster-Carr Supply Company</td><td>4429K422</td><td>Reducing tube diameter inside the Desiccator to adapt to Air-operated Syringe System (Step: Elastomer Injection)</td></tr><tr><td>Coupling, Adapter, Straight, Reducing, Bushing, Hex, 1/4 NPT Male X 1/8 NPT Female, Brass</td><td>McMaster-Carr Supply Company</td><td>4757T91</td><td>Reducing tube diameter inside the Desiccator to adapt to Air-operated Syringe System (Step: Elastomer Injection)</td></tr><tr><td>Coupling, Adapter, Straight, Vacuum Barb 1/4&quot; ID Tube X 1/8 NPT Female, Brass</td><td>McMaster-Carr Supply Company</td><td>44555K124</td><td>Reducing tube diameter inside the Desiccator to adapt to Air-operated Syringe System (Step: Elastomer Injection)</td></tr><tr><td>Syringe Adapters, Air Operated, 30/50 ml</td><td>EWD Solutions</td><td>JEN-JG30A-X6</td><td>Air operated syringe adapter on the inside of the Desiccator; must be compatible with syringes used to hold elastomer (Step: Elastomer Injection)</td></tr><tr><td>Gauge, Dual-Scale Vacuum, 2-1/2&quot; Dial, 1/4 NPT Male, Bottom Connector, 30&quot; Hg-0, Steel Case</td><td>McMaster-Carr Supply Company</td><td>4002K11</td><td>Vacuum Gauge (Step: Elastomer Injection)</td></tr><tr><td>Gauge, Dual-Scale Vacuum and Compound, 3-1/2&quot; Dial, 1/4 NPT Male, Center Back, 30&quot; Hg-0, 100 PSI, Steel Case</td><td>McMaster-Carr Supply Company</td><td>4004K616</td><td>Pressure Gauge leading to Air-operated Syringe System (Step: Elastomer Injection)</td></tr><tr><td>Oven, Vacuum, Isotemp, Economy&amp;nbsp;</td><td>Fisher Scientific</td><td>280A</td><td>Standard non-vacuum oven can be used (Step: Curing &amp;amp; Demolding)</td></tr><tr><td>Solidworks CAD</td><td>Dassault Syst&amp;egrave;mes</td><td>Solidworks Research Subscription</td><td>Other CAD Software can be used for mold master and mold design (Step: Mold Design &amp;amp; Production)</td></tr></tbody></table>

rapid and low-cost prototyping of medical devices using 3d printed molds for liquid injection molding

生物惰性的弹性体，如硅树脂是用于医疗装置的制造有利的材料，但形成和使用传统的液体注射成型工艺的固化这些弹性体可以是一个昂贵的过程中，由于模具和设备的成本。作为一个结果，它在传统上一直不切实际的使用液体注射成型的低成本，快速原型应用程序。我们已经发明了一种方法，用于快速和低成本的生产液态弹性体的注塑装置，它利用进行模具设计和修饰的干燥器作为注射系统熔融沉积建模三维打印机。成本低，在这种技术的快速周转时间降低门槛迭代设计和原型制作复杂的弹性体装置。此外，在这个过程中开发的CAD模型可以购买适合于金属模具的模具设计，从而实现了容易过渡到一个传统的注塑成型工艺。我们已经用这种技术制造intravagINAL探头涉及复杂的几何形状，以及包覆成型在金属部件，使用中的学术研究实验室常用的工具。然而，这种技术可以很容易地适应创建许多其他应用的液体注射成型设备。

在图14和15的模具和阴道探头演示本文中介绍的过程中有代表性的结果。 <img alt="图14" fo:content-width="5in" src="/files/ftp_upload/51745/51745fig14highres.jpg" width="500" /> 图14。完全组装模具。完全组装模具阴道探头装置。 <img alt="图15" fo:content-width="5in" src="/files/ftp_upload/51745/51745fig15highres.jpg" width="500" /> 该设备相同的设备。 二）侧视图的杯状尖如图15所示。阴道内探测设备。决赛阴道探头装置A）的前视图。杯状结构由六个包覆成型的钛电极，以及一个不锈钢管，作为一个有限元啤酒容器的光纤探头。 具体使用该设备的埃特马迪等 12,13描述。用于创建所述阴道探针的模具从ABS430材料使用的是尺寸uPrint加三维打印机制作。一个模具需要大约1卷ABS430材料售价为140美元卷轴的阴道探头。花了大约1.5天，打印所有八件模具。 医疗级双组分铂固化有机硅专为LIM应用（PN40029）用于此应用程序。包覆成型于主体硅氧烷是定制的不锈钢管中，修饰的USB电缆，一些电线，和钛电极，这是通过在模具中精心设计的对准和定位的几何形状保持就位硅酮注射过程。一管子在上所述阴道探针的杯形结构的基部被暴露并且具有在管行事的端部的玻璃窗作为一个插座为用于光学测量的光纤束。这是添加有机硅固化和使用过程中记录的脱模后的唯一外部特征。 根据所期望的几何形状，以及是否包覆成型时所需的特定结果可能不同。所述阴道探针表明创建复杂的几何形状，如一个薄的杯状结构是可能与FDM三维打印机，但更简单的几何形状可能会需要更少的模具件，少的模具材料，并且将更快到三维打印。利用较高分辨率3D印刷技术如SLA可能能够提供更高的分辨率，更精细的几何形状，和优良的表面光洁度可消除需要手动完成模具。使用所描述的技术中，许多不同的组件的包覆成​​型可以，只要模具的设计是经过精心实施完成。

Watch this Scientific Journal Video about Rapid and Low-cost Prototyping of Medical Devices Using 3D Printed Molds for Liquid Injection Molding at JoVE.com

Rapid and Low-cost Prototyping of Medical Devices Using 3D Printed Molds for Liquid Injection Molding

我们已通过使用用于模具的设计和改进的干燥器熔融沉积建模三维打印机作为液体喷射系统设计了一种方法用于低成本和液态弹性体橡胶注射成型设备的快速原型。

医疗器械的使用3D印刷模具的液体注射成型快速，低成本原型

Biologically inert elastomers such as silicone are favorable materials for medical device fabrication, but forming and curing these elastomers using ...

rapid-low-cost-prototyping-medical-devices-using-3d-printed-molds-for

Universidad San Sebastian

Research

JoVE Journal

Bioengineering

19.8K 次观看.  University of California, San Francisco. 我们已通过使用用于模具的设计和改进的干燥器熔融沉积建模三维打印机作为液体喷射系统设计了一种方法用于低成本和液态弹性体橡胶注射成型设备的快速原型。 

视频: Rapid and Low-cost Prototyping of Medical Devices Using 3D Printed Molds for Liquid Injection Molding

High Throughput Microfluidic Rapid and Low Cost Prototyping Packaging Methods

In this work, 3 different packaging and assembly techniques are presented. They can be classified into two categories: one-time use and reusable packaging techniques.
The one-time use packaging technique employs UV-based and temperature curing epoxies to connect microtubes to access holes, wire-bonding for integrated circuit connections, and silver epoxy for electrical connections. This method is based on a robust assembly technique that can support relatively high pressure close to 1 psi and does not need any support to strengthen the microfluidic architecture.
Reusable packaging techniques consist of PDMS-based microtube interconnectors and anisotropic adhesive films for electrical connections. These devices are more sensitive and fragile. Consequently, Plexiglas support is added to the microfluidic structure to improve the electrical contact when anisotropic adhesive films are used, and also to strengthen the microfluidic architecture. In addition, a micromanipulator is needed to maintain tubes while using a thin PDMS layer to connect them to the access holes. Different PDMS layer thicknesses, ranging from 0.45-3 mm, are tested to compare the best adherence versus injection rates. Applied injection rates are varied from 50-300 &#956;l/hr for 0.45-3 mm PDMS layers, respectively. These techniques are mainly applicable for low-pressure applications. However, they can be extended for high-pressure ones through plasma-oxygen process to permanently seal the PDMS to glass substrates. The main advantage of this technique, besides the fact that it is reusable, consists of keeping the device observable when the microchannel length is very short (in the range of 3 mm or lower).

In this article we describe different techniques for microfluidic rapid prototyping platforms. The proposed techniques are based on ultraviolet (UV) sensitive and temperature curing epoxies, polydimethylsiloxane (PDMS) based tubing, wire-bonding, and anisotropic adhesive films. The assembling procedures presented are developed for both one-time use devices as well as reusable microfluidic systems.

In this work, 3 different packaging and assembly techniques are presented. They can be classified into two categories: one-time use and reusable packaging ...

科研

生物工程

Printing Thermoresponsive Reverse Molds for the Creation of Patterned Two-component Hydrogels for 3D Cell Culture

Bioprinting is an emerging technology that has its origins in the rapid prototyping industry. The different printing processes can be divided into contact bioprinting1-4 (extrusion, dip pen and soft lithography), contactless bioprinting5-7 (laser forward transfer, ink-jet deposition) and laser based techniques such as two photon photopolymerization8. It can be used for many applications such as tissue engineering9-13, biosensor microfabrication14-16 and as a tool to answer basic biological questions such as influences of co-culturing of different cell types17. Unlike common photolithographic or soft-lithographic methods, extrusion bioprinting has the advantage that it does not require a separate mask or stamp. Using CAD software, the design of the structure can quickly be changed and adjusted according to the requirements of the operator. This makes bioprinting more flexible than lithography-based approaches.
Here we demonstrate the printing of a sacrificial mold to create a multi-material 3D structure using an array of pillars within a hydrogel as an example. These pillars could represent hollow structures for a vascular network or the tubes within a nerve guide conduit. The material chosen for the sacrificial mold was poloxamer 407, a thermoresponsive polymer with excellent printing properties which is liquid at 4 &deg;C and a solid above its gelation temperature ~20 &deg;C for 24.5% w/v solutions18. This property allows the poloxamer-based sacrificial mold to be eluted on demand and has advantages over the slow dissolution of a solid material especially for narrow geometries. Poloxamer was printed on microscope glass slides to create the sacrificial mold. Agarose was pipetted into the mold and cooled until gelation. After elution of the poloxamer in ice cold water, the voids in the agarose mold were filled with alginate methacrylate spiked with FITC labeled fibrinogen. The filled voids were then cross-linked with UV and the construct was imaged with an epi-fluorescence microscope.

A bioprinter was used to create patterned hydrogels based on a sacrificial mold. The poloxamer mold was backfilled with a second hydrogel and then eluted, leaving voids which were filled with a third hydrogel. This method uses fast elution and good printability of poloxamer to generate complex architectures from biopolymers.

打印温敏反向模具图案创作的双组分水凝胶的三维细胞培养

Bioprinting is an emerging technology that has its origins in the rapid prototyping industry. The different printing processes can be divided into contact ...

免疫与感染

A Soft Tooling Process Chain for Injection Molding of a 3D Component with Micro Pillars

The purpose of this paper is to present the method of a soft tooling process chain employing Additive Manufacturing (AM) for fabrication of injection molding inserts with micro surface features. The Soft Tooling inserts are manufactured by Digital Light Processing (vat photo polymerization) using a photopolymer that can withstand relatively high temperaturea. The part manufactured here has four tines with an angle of 60&#176;. Micro pillars (&#216;200 &#181;m, aspect ratio of 1) are arranged on the surfaces by two rows. Polyethylene (PE) injection molding with the soft tooling inserts is used to fabricate the final parts. This method demonstrates that it is feasible to obtain injection-molded parts with microstructures on complex geometry by additive manufactured inserts. The machining time and cost is reduced significantly compared to conventional tooling processes based on computer numerical control (CNC) machining. The dimensions of the micro features are influenced by the applied additive manufacturing process. The lifetime of the inserts determines that this process is more suitable for pilot production. The precision of the inserts production is limited by the additive manufacturing process as well.

A protocol for fabricating injection molding inserts for complex geometry with micro features on surfaces employing Additive Manufacturing (AM) is presented.

微柱3D 构件注塑成型的软加工工艺链

The purpose of this paper is to present the method of a soft tooling process chain employing Additive Manufacturing (AM) for fabrication of injection ...

工程学

Design and Development of a Three-Dimensionally Printed Microscope Mask Alignment Adapter for the Fabrication of Multilayer Microfluidic Devices

This project aims to develop an easy-to-use and cost-effective platform for the fabrication of precise, multilayer microfluidic devices, which typically can only be achieved using costly equipment in a clean room setting. The key part of the platform is a three dimensionally (3D) printed microscope mask alignment adapter (MMAA) compatible with regular optical microscopes and ultraviolet (UV) light exposure systems. The overall process of creating the device has been vastly simplified because of the work done to optimize the device design. The process entails finding the proper dimensions for the equipment available in the laboratory and 3D-printing the MMAA with the optimized specifications. Experimental results show that the optimized MMAA designed and manufactured by 3D printing performs well with a common microscope and light exposure system. Using a master mold prepared by the 3D-printed MMAA, the resulting microfluidic devices with multilayered structures contain alignment errors of &lt;10 &#181;m, which is sufficient for common microchips. Although human error through transportation of the device to the UV light exposure system can cause larger fabrication errors, the minimal errors achieved in this study are attainable with practice and care. Furthermore, the MMAA can be customized to fit any microscope and UV exposure system by making changes to the modeling file in the 3D printing system. This project provides smaller laboratories with a useful research tool as it only requires the use of equipment that is typically already available to laboratories that produce and use microfluidic devices. The following detailed protocol outlines the design and 3D printing process for the MMAA. In addition, the steps for procuring a multilayer master mold using the MMAA and producing poly(dimethylsiloxane) (PDMS) microfluidic chips is also described herein.

This project allows small laboratories to develop an easy-to-use platform for the fabrication of precise multilayer microfluidic devices. The platform consists of a three-dimensionally printed microscope mask alignment adapter using which multilayer microfluidic devices with alignment errors of &lt;10 &#181;m were achieved.

设计和开发用于制造多层微流体设备的三维打印显微镜面膜对齐适配器

This project aims to develop an easy-to-use and cost-effective platform for the fabrication of precise, multilayer microfluidic devices, which typically ...

Assembly and Characterization of an External Driver for the Generation of Sub-Kilohertz Oscillatory Flow in Microchannels

Microfluidic technology has become a standard tool in chemical and biological laboratories for both analysis and synthesis. The injection of liquid samples, such as chemical reagents and cell cultures, is predominantly accomplished through steady flows that are typically driven by syringe pumps, gravity, or capillary forces. The use of complementary oscillatory flows is seldom considered in applications despite its numerous advantages as recently demonstrated in the literature. The significant technical barrier to the implementation of oscillatory flows in microchannels is likely responsible for the lack of its widespread adoption. Advanced commercial syringe pumps that can produce oscillatory flow, are often more expensive and only work for frequencies less than 1 Hz. Here, the assembly and operation of a low-cost, plug-and-play type speaker-based apparatus that generates oscillatory flow in microchannels is demonstrated. High-fidelity harmonic oscillatory flows with frequencies ranging from 10-1000 Hz can be achieved along with independent amplitude control. Amplitudes ranging from 10-600 &#181;m can be achieved throughout the entire range of operation, including amplitudes &#62; 1 mm at the resonant frequency, in a typical microchannel. Although the oscillation frequency is determined by the speaker, we illustrate that the oscillation amplitude is sensitive to fluid properties and channel geometry. Specifically, the oscillation amplitude decreases with increasing channel circuit length and liquid viscosity, and in contrast, the amplitude increases with increasing speaker tube thickness and length. Additionally, the apparatus requires no prior features to be designed on the microchannel and is easily detachable. It can be used simultaneously with a steady flow created by a syringe pump to generate pulsatile flows.

The protocol demonstrates a convenient method to produce harmonic oscillatory flow from 10-1000 Hz in microchannels. This is performed by interfacing a computer-controlled speaker diaphragm to the microchannel in a modular manner.

用于在微通道中产生亚千赫兹振荡流的外部驱动器的组装和表征

Microfluidic technology has become a standard tool in chemical and biological laboratories for both analysis and synthesis. The injection of liquid ...

Fabrication of Custom Agarose Wells for Cell Seeding and Tissue Ring Self-assembly Using 3D-Printed Molds

Engineered tissues are being used clinically for tissue repair and replacement, and are being developed as tools for drug screening and human disease modeling. Self-assembled tissues offer advantages over scaffold-based tissue engineering, such as enhanced matrix deposition, strength, and function. However, there are few available methods for fabricating 3D tissues without seeding cells on or within a supporting scaffold. Previously, we developed a system for fabricating self-assembled tissue rings by seeding cells into non-adhesive agarose wells. A polydimethylsiloxane (PDMS) negative was first cast in a machined polycarbonate mold, and then agarose was gelled in the PDMS negative to create ring-shaped cell seeding wells. However, the versatility of this approach was limited by the resolution of the tools available for machining the polycarbonate mold. Here, we demonstrate that 3D-printed plastic can be used as an alternative to machined polycarbonate for fabricating PDMS negatives. The 3D-printed mold and revised mold design is simpler to use, inexpensive to produce, and requires significantly less agarose and PDMS per cell seeding well. We have demonstrated that the resulting agarose wells can be used to create self-assembled tissue rings with customized diameters from a variety of different cell types. Rings can then be used for mechanical, functional, and histological analysis, or for fabricating larger and more complex tubular tissues.

This protocol describes a platform for fabricating self-assembled tissue rings in variable sizes using a customized 3D-printed plastic mold. PDMS negatives are cured in the 3D-printed mold; then agarose is cast in the cured PDMS negatives. Cells are seeded into the resulting agarose wells where they aggregate into tissue rings.

用 3 d-印刷模具制作细胞播种和组织环自组装用的自定义琼脂糖井

Engineered tissues are being used clinically for tissue repair and replacement, and are being developed as tools for drug screening and human disease ...

Custom Engineered Tissue Culture Molds from Laser-etched Masters

As the field of tissue engineering has continued to mature, there has been increased interest in a wide range of tissue parameters, including tissue shape. Manipulating tissue shape on the micrometer to centimeter scale can direct cell alignment, alter effective mechanical properties, and address limitations related to nutrient diffusion. In addition, the vessel in which a tissue is prepared can impart mechanical constraints on the tissue, resulting in stress fields that can further influence both the cell and matrix structure. Shaped tissues with highly reproducible dimensions also have utility for in vitro assays in which sample dimensions are critical, such as whole tissue mechanical analysis.
This manuscript describes an alternative fabrication method utilizing negative master molds prepared from laser etched acrylic: these molds perform well with polydimethylsiloxane (PDMS), permit designs with dimensions on the centimeter scale and feature sizes smaller than 25 &#181;m, and can be rapidly designed and fabricated at a low cost and with minimal expertise. The minimal time and cost requirements allow for laser etched molds to be rapidly iterated upon until an optimal design is determined, and to be easily adapted to suit any assay of interest, including those beyond the field of tissue engineering.

Herein we present a rapid, facile, and low-cost method for fabricating custom polydimethylsiloxane molds that can be used for producing hydrogel-based engineered tissues with complex geometries. We additionally describe results from mechanical and histological assessments conducted on engineered cardiac tissues produced using this technique.

由激光蚀刻大师定制的组织培养模具

As the field of tissue engineering has continued to mature, there has been increased interest in a wide range of tissue parameters, including tissue ...

Three-dimensional Printing of Thermoplastic Materials to Create Automated Syringe Pumps with Feedback Control for Microfluidic Applications

Microfluidics has become a critical tool in research across the biological, chemical, and physical sciences. One important component of microfluidic experimentation is a stable fluid handling system capable of accurately providing an inlet flow rate or inlet pressure. Here, we have developed a syringe pump system capable of controlling and regulating the inlet fluid pressure delivered to a microfluidic device. This system was designed using low-cost materials and additive manufacturing principles, leveraging three-dimensional (3D) printing of thermoplastic materials and off-the-shelf components whenever possible. This system is composed of three main components: a syringe pump, a pressure transducer, and a programmable microcontroller. Within this paper, we detail a set of protocols for fabricating, assembling, and programming this syringe pump system. Furthermore, we have included representative results that demonstrate high-fidelity, feedback control of inlet pressure using this system. We expect this protocol will allow researchers to fabricate low-cost syringe pump systems, lowering the entry barrier for the use of microfluidics in biomedical, chemical, and materials research.

Here we present a protocol to construct a pressure-controlled syringe pump to be used in microfluidic applications. This syringe pump is made from an&#160;additively manufactured body, off-the-shelf hardware, and open-source electronics. The resulting system is low-cost, straightforward to build, and delivers well-regulated fluid flow to enable rapid microfluidic research.

三维热塑性材料的印刷, 以创建自动注射器泵的反馈控制微流控应用

Microfluidics has become a critical tool in research across the biological, chemical, and physical sciences. One important component of microfluidic ...

3D Analysis of Multi-cellular Responses to Chemoattractant Gradients

Various limitations of 2D cell culture systems have sparked interest in 3D cell culture and analysis platforms, which would better mimic the spatial and chemical complexity of living tissues and mimic in vivo tissue functions. Recent advances in microfabrication technologies have facilitated the development of 3D in vitro environments in which cells can be integrated into a well-defined extracellular matrix (ECM) and a defined set of soluble or matrix associated biomolecules. However, technological barriers have limited their widespread use in research laboratories. Here, we describe a method to construct simple devices for 3D culture and experimentation with cells and multicellular organoids in 3D microenvironments with a defined chemoattractant gradient. We illustrate the use of this platform for analysis of the response of epithelial cells and organoids to gradients of growth factors, such as epidermal growth factor (EGF). EGF gradients were stable in the devices for several days leading to directed branch formation in breast organoids. This analysis allowed us to conclude that collective gradient sensing by groups of cells is more sensitive vs. single cells. We also describe the fabrication method, which does not require photolithography facilities nor advanced soft lithography techniques. This method will be helpful to study 3D cellular behaviors in the context of the analysis of development and pathological states, including cancer.

We describe a method to construct devices for 3D culture and experimentation with cells and multicellular organoids. This device allows analysis of cellular responses to soluble signals in 3D microenvironments with defined chemoattractant gradients. Organoids are better than single cells at detection of weak noisy inputs.

趋化梯度多细胞响应的三维分析

Various limitations of 2D cell culture systems have sparked interest in 3D cell culture and analysis platforms, which would better mimic the spatial and ...

Design of an Open-Source, Low-Cost Bioink and Food Melt Extrusion 3D Printer

Three-dimensional (3D) printing is an increasingly popular manufacturing technique that allows highly complex objects to be fabricated with no retooling costs. This increasing popularity is partly driven by falling barriers to entry such as system set-up costs and ease of operation. The following protocol presents the design and construction of an Additive Manufacturing Melt Extrusion (ADDME) 3D printer for the fabrication of custom parts and components. ADDME has been designed with a combination of 3D-printed, laser-cut, and online-sourced components. The protocol is arranged into easy-to-follow sections, with detailed diagrams and parts lists under the headings of framing, y-axis and bed, x-axis, extrusion, electronics, and software. The performance of ADDME is evaluated through extrusion testing and 3D printing of complex objects using viscous cream, chocolate, and Pluronic F-127 (a model for bioinks). The results indicate that ADDME is a capable platform for the fabrication of materials and constructs for use in a wide range of industries. The combination of detailed diagrams and video content facilitates access to low-cost, easy-to-operate equipment for individuals interested in 3D printing of complex objects from a wide range of materials.

The aim of this work is to design and construct a reservoir-based melt extrusion three-dimensional printer made from open-source and low-cost components for applications in the biomedical and food printing industries.

设计开源、低成本生物墨水和食品熔炼挤出3D打印机

Three-dimensional (3D) printing is an increasingly popular manufacturing technique that allows highly complex objects to be fabricated with no retooling ...