This work was supported by the EC within the framework of the STIFF-FLOP FP7-ICT-2011.2.1 European Project (#287728).

注意：此协议描述了单个模块，它包括流体腔室，加强槽，致动管线和外部护套的制造阶段。下面的过程有在通风橱，穿着白大褂和手套出于安全原因被执行。如前面提到的，弹性单元的制造过程是基于依次使用设计CAD软件模具。它们是由在图2中所示和表1中所列的 13件。 1.制备有机硅<ol><li>称量12个克A部分和12克B部分在相同的塑料或玻璃培养皿并混合，搅拌。 注意：材料的比例可以根据所用的特定的有机硅发生变化，在这种情况下，它由两部分组成：一部分甲（基）和B部分（催化剂）。它们被用在比例1A：1B的重量。 </li><li>将含有该混合物的玻璃编有机硅材料的脱气机在1巴的真空压力。保持玻璃在真空下，直到所有的气泡从硅材料中除去。对于所采用的聚硅氧烷脱气过程大约需要10分钟。一旦材料是完全无气泡的存在下，还原大气压到机器并使用硅酮。 </li></ol> 2.制作的含硅模块<ol><li>大会的模具。 <ol><li>插入该加强气缸和腔室的顶部成cap_A（图3a）。 </li><li>关闭弹cap_A的第二层周围。 </li></ol></li><li>第一有机硅铸造。 <ol><li>倾里面的组装模具到炮弹（图3b）的边缘的硅酮。 </li><li>放置在烘箱的模具在60℃下进行约30分钟。 </li></ol></li><li>重排的模具。 <ol><li>除去外部壳和cap_A（ 图3C）。 </li><li>插入从腔室的碱和内部cap_B（ 图3d），该加强气缸的气缸。 </li><li>再次关闭弹模块周围，向上为了具有的模块的顶表面和所述壳体（ 图3e）的边缘之间10mm的间隙滑动为10mm它们。 </li></ol></li><li>二硅铸造。 <ol><li>倾内部重排的模具到壳的边缘上的顶侧（即也达至加强气缸）（ 图3f）硅氧烷。 </li><li>把模具放入烘箱中，在60℃下进行约30分钟。 </li><li>去除外部壳，cap_B和腔室（除了所述加强气缸）（ 图3g）。 </li></ol></li></ol> 3.插入管<ol><li>切成3管到同一个期望的长度（300毫米例如）。 </li><li>放含硅胶围绕每个管的一端10毫米，没有作业强县管。 </li><li>插入内部的2毫米专用的含硅单元（图3小时 ）通道的管中。 </li><li>允许在室温下12分钟的固化时间，或将模块的烘箱内，在较高的温度（50° - 60°），以加快干燥过程。 </li></ol> 4.加工的轧花编织鞘<ol><li>裁减700毫米的可膨胀的编织鞘（模块的约15倍的高度）的。 </li><li>插入30毫米直径和250毫米的护套内部长度的金属圆柱体。 </li><li>向下推并通过滑过缸迫使护套，以便创建卷曲。 </li><li>机械地固定所述护套在适当位置的夹紧和热用加热枪在350℃2-3分钟，直到获得一个永久变形。 </li><li>让护套冷静下来，取出内筒。 </li></ol>其外部护套5.整合<ol><li>传通过cap_C的孔管中。 </li><li>倒3克硅到cap_C。 </li><li>夹紧cap_C到支撑比所述工作平面更高。 </li><li>插入预先制成cap_C模块的底侧。 </li><li>滑动模块周围卷曲鞘。 </li><li>推里面cap_C护套的第一卷曲都蘸到新浇铸硅氧烷（图3I）。 </li><li>把模具放入烘箱中，在60℃下约20分钟。 </li><li>从点5.1-5.6重复同样的步骤来解决这个鞘上侧，使用cap_D（ 图3J）。 </li><li>删除cap_C和cap_D。 </li><li>拆下气缸中部（ 图3K）。 </li></ol> 6.制造的颗粒干扰膜<ol><li>倒5克液体乳胶成玻璃胶。 </li><li>浸入气缸对膜的液体胶乳内侧（最后在图2中所示部件），直到表面完全覆盖。 </li><li>让罩20分钟下干燥。 </li><li>重复点6.2和6.3。 </li><li>从模具中取出该膜。 </li></ol> 7.插入颗粒干扰膜<ol><li>切的管（直径2mm），以所希望的长度（300毫米例如）。 </li><li>切平方一块约100毫米2尼龙组织并关闭管的一端与使用塑料石蜡膜或强力胶此组织。 </li><li>称取4克咖啡粉，并填写膜。 </li><li>插入管（端与过滤器）的填充膜的内部，并用塑料膜石蜡修复它围绕管。 </li><li>在管（膜变得更硬）的另一侧施加真空。 </li><li>将含硅模块（ 图升）的空中央通道内的膜。 </li><li>胶水硬化膜的端部的硅氧烷模块。 </li><li>紧密围绕顶环该模块（ 图3米）的一面。 </li><li>倒入2克硅氧烷成环以平的表面上。 </li><li>让下罩或在烘箱中在60℃的有机硅干。 </li><li>取下戒指。 </li><li>从分7.8至7.11的底部（ 图3N）重复。 </li></ol>

<ol>
	<li>Scott, D. J., 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=Completely+transvaginal+NOTES+cholecystectomy+using+magnetically+anchored+instruments.">Completely transvaginal NOTES cholecystectomy using magnetically anchored instruments.</a> Surgical Endoscopy. 21, 2308-2316 (2007).</li><li>Vitiello, V., Lee, S., Cundy, T., Yang, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Emerging+Robotic+Platforms+for+Minimally+Invasive+Surgery.">Emerging Robotic Platforms for Minimally Invasive Surgery.</a> IEEE Reviews in Biomedical Engineering. 6, 111-126 (2013).</li><li>Vyas, L., Aquino, D., Kuo, C. -. H., Dai, J. S., Dasgupta, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flexible+Robotics.">Flexible Robotics.</a> BJU International. 107, 187-189 (2011).</li><li>Degani, A., Choset, H., Wolf, A., Zenati, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+articulated+robotic+probe+for+minimally+invasive+surgery.">Highly articulated robotic probe for minimally invasive surgery.</a> Proceedings of IEEE International Conference on Robotics and Automation. , 4167-4172 (2006).</li><li>Bajo, A., Dharamsi, L. M., Netterville, J. L., Garrett, C. G., Simaan, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robotic-assisted+micro-surgery+of+the+throat:+The+trans-nasal+approach.">Robotic-assisted micro-surgery of the throat: The trans-nasal approach.</a> , 232-238 (2013).</li><li>Burgner, J., Swaney, P. J., Lathrop, R. A., Weaver, K. D., Webster, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Debulking+From+Within:+A+Robotic+Steerable+Cannula+for+Intracerebral+Hemorrhage+Evacuation.">Debulking From Within: A Robotic Steerable Cannula for Intracerebral Hemorrhage Evacuation.</a> IEEE Transactions on Biomedical Engineering. 60, 2567-2575 (2013).</li><li>Tortora, G., Ranzani, T., De Falco, I., Dario, P., Menciassi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Miniature+Robot+for+Retraction+Tasks+under+Vision+Assistance+in+Minimally+Invasive+Surgery.">A Miniature Robot for Retraction Tasks under Vision Assistance in Minimally Invasive Surgery.</a> Robotics. 3, 70-82 (2014).</li><li>Laschi, C., Cianchetti, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Soft+Robotics:+new+perspectives+for+robot+bodyware+and+control.">Soft Robotics: new perspectives for robot bodyware and control.</a> Frontiers in Bioengineering and Biotechnology. 2, (2014).</li><li>Loeve, A., Breedveld, P., Dankelman, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Scopes+too+flexible...and+too+stiff.">Scopes too flexible...and too stiff.</a> Pulse, IEEE. 1, 26-41 (2010).</li><li>Cianchetti, M., Follador, M., Mazzolai, B., Dario, P., Laschi, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+and+development+of+a+soft+robotic+octopus+arm+exploiting+embodied+intelligence.">Design and development of a soft robotic octopus arm exploiting embodied intelligence.</a> , 5271-5276 (2012).</li><li>Smith, K., Kier, W. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trunks,+tongues,+and+tentacles:+Moving+with+skeletons+of+muscle.">Trunks, tongues, and tentacles: Moving with skeletons of muscle.</a> American Scientist. 77, 28-35 (1989).</li><li>Walker, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Some+issues+in+creating+&#8220;invertebrate&#8221;+robots.">Some issues in creating &#8220;invertebrate&#8221; robots.</a> , (2000).</li><li>McMahan, W., Jones, B., Walker, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+and+implementation+of+a+multi-section+continuum+robot:+Air-octor.">Design and implementation of a multi-section continuum robot: Air-octor.</a> IEEE/RSJ International Conference on Intelligent Robots and Systems. , 2578-2585 (2005).</li><li>Laschi, C., Mazzolai, B., Cianchetti, M., Margheri, L., Follador, M., Dario, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Soft+Robot+Arm+Inspired+by+the+Octopus.">A Soft Robot Arm Inspired by the Octopus.</a> Advanced Robotics (Special Issue on Soft Robotics). 26, 709-727 (2012).</li><li>Chianchetti, 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=Soft+robotics+technologies+to+address+shortcomings+in+today&#8217;s+minimally+invasive+surgery:+the+STIFF-FLOP+approach.">Soft robotics technologies to address shortcomings in today&#8217;s minimally invasive surgery: the STIFF-FLOP approach.</a> Soft Robotics. 1, 122-131 (2014).</li><li>Cheng, N. G., 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=Design+and+Analysis+of+a+Robust,+Low-cost,+Highly+Articulated+manipulator+enabled+by+jamming+of+granular+media.">Design and Analysis of a Robust, Low-cost, Highly Articulated manipulator enabled by jamming of granular media.</a> , 4328-4333 (2012).</li><li>Cianchetti, M., Ranzani, T., Gerboni, G., De Falco, I., Laschi, C., Menciassi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=STIFF-FLOP+Surgical+Manipulator:+mechanical+design+and+experimental+characterization+of+the+single+module.">STIFF-FLOP Surgical Manipulator: mechanical design and experimental characterization of the single module.</a> Proceedings of IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS. , 3576-3581 (2013).</li><li>De Falco, I., Cianchetti, M., Menciassi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+soft+and+controllable+stiffness+manipulator+for+minimally+invasive+surgery:+preliminary+characterization+of+the+modular+design).">A soft and controllable stiffness manipulator for minimally invasive surgery: preliminary characterization of the modular design).</a> Proceedings of 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). , (2014).</li><li>De Falco, I., Cianchetti, M., Menciassi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=STIFF-FLOP+surgical+manipulator:+design+and+preliminary+motion+evaluation).">STIFF-FLOP surgical manipulator: design and preliminary motion evaluation).</a> Proceedings of 4th WorkShop on Computer/Robot Assisted Surgery (CRAS). , 131-134 (2014).</li></ol>

The authors have nothing to disclose.

The technique described in this protocol enables the fabrication of a pneumatically actuated soft unit usable for modular compliant structures. Thanks to the design of the molds and their simple assembly, it is possible to fabricate one complete module in about 4 hours with 7 main steps. The process of fabrication involves specific materials, which are easily available, and work should be carried out under a fume hood. An external set up including air valves, air compressor and vacuum pump is necessary to activate the mo...

在医疗领域最近的趋势正在推动在外科手术的侵入性的降低。微创外科（MIS）已成功地在过去的几年中对于腹部手术改善。 MIS过程基于使用通过放置在腹壁四个或五个接入点（套管针）介绍的工具。为了减少套管针的数量，器械可通过单端口腹腔镜（SPL）或自然腔腔道内窥镜手术（NOTES）1插入。这些程序防止外部醒目的伤痕，但会增加在执行手术难度的临床医生。这个限制主要是由于访问的已缩减点，并把该文书，这是不能够避免或通过周围器官2的刚性和半刚性的性质，3。敏捷和运动可以使用改进的铰接式和超冗余机器人可覆盖一个更宽的和更复杂的工作区，第我们能够在身体的特定目标，以更容易地达到了4，5，6和工作，作为必要时7回缩系统。灵活的机械手可以提高组织的合规性，从而使接触比传统工具更安全。 然而，这些机械手通常缺乏当达到目标稳定性并且通常它们无法控制与周围组织8，接触件9。研究生物结构，诸如章鱼臂 10和象鼻11，最近已激发的设计灵活的，变形的，符合机械手与自由（自由度）度的冗余数量和可控刚度12。这些种类的设备利用被动弹簧，智能材料，气动元件，或筋13，14，15，通常，操纵器制造为柔软而有弹性的材料并不能保证高的力的产生。 Ť他僵硬FLOP（刚度控制的灵活和可学习机械手进行外科手术）机械手已被最近提出作为一种新型的手术设备，用于笔记和SPL灵感来自于章鱼的能力。为了克服以往的软机器人的局限性，它具有柔软的身体以及高灵活性，高力和可控刚度16。 操纵器的体系结构是基于模块化的方法：多个单元，具有相同的结构和功能，是集成在一起。单个单元示于图1，它是根据由一个多相制造而得到的弹性圆柱体。组装步骤的模具组件和铸造工艺的使三个空腔（用于流体致动），以及一个中空的中心通道17（用于容纳粒状干扰系机构 18）将要被嵌入。腔室被放置在120℃，从而使IR结合通胀产生全方位的运动和伸长率。另外一个外部编织鞘被放置在外部时加压，从而优化了腔室的致动的效果在模块运动（弯曲和伸长率），以限制的流体腔室的径向向外扩张。 中心通道容纳填充有颗粒材料的外部膜构成的圆柱形设备。当的真空压力被施加，它改变它的弹性性能引起的硬化从而影响整个模块的属性。 运动和刚度性能由外部设置，包括一空气压缩机和三个压力阀致动腔室，一个真空泵用于激活真空中该硬化信道进行控制。直观的用户界面，允许在模块内部驱动和真空压力的控制。 本文详细介绍了fabricatio这个机械手和报告基本运动能力最显著结果的单个模块的n个过程。考虑到设备的模块化性质，制造和只是一个单一的模块的性能的评估还使得结果进行扩展，并预测一个多模块操纵器集成两个或多个模块的基本行为。

<table border="0">
	<tbody>
		<tr>
			<td>Ecoflex 00-50 Trial Kit</td>
			<td>SmoothOn</td>
			<td></td>
			<td>Used for the fabrication of the soft unit, combining equal amounts of liquid parts A (the base) and B (the catalyst)</td>
		</tr>
		<tr>
			<td>Latex</td>
			<td>Antichit&#224; Belsito</td>
			<td></td>
			<td>Used for the fabrication of the granular jamming membrane</td>
		</tr>
		<tr>
			<td>Peroxide-Cured Silicone Tubing</td>
			<td>Cole Parmer</td>
			<td>T-06411-59</td>
			<td>Used for actuating the chambers and applying vacuum</td>
		</tr>
		<tr>
			<td>PET expandable braided sleeving</td>
			<td>RS</td>
			<td>408-249</td>
			<td>Used for the fabrication of the external braided sheath</td>
		</tr>
		<tr>
			<td>Silicone Rubber</td>
			<td>Momentive</td>
			<td>127374</td>
			<td>Used to fix the actuation tubes to the module</td>
		</tr>
		<tr>
			<td>Parafilm</td>
			<td>Cole Parmer</td>
			<td>EW-06720-40</td>
			<td>Used to fix the latex membrane to the vacuum tube</td>
		</tr>
		<tr>
			<td>Fume hood Secuflow</td>
			<td>Groupe Waldner</td>
			<td></td>
			<td>Working space</td>
		</tr>
		<tr>
			<td>Precision scale</td>
			<td>KERN EW</td>
			<td></td>
			<td>Used to weight silicone, latex and coffee powder</td>
		</tr>
		<tr>
			<td>Oven/degasser</td>
			<td>Heraeus</td>
			<td></td>
			<td>Used to degass the silicone and reduce its cure time</td>
		</tr>
		<tr>
			<td>Vacuum pump</td>
			<td>DVP Vacuum Technology</td>
			<td></td>
			<td>Used to apply vacuum to the latex membrane</td>
		</tr>
	</tbody>
</table>

design and fabrication of an elastomeric unit for soft modular robots in minimally invasive surgery

近年来，软机器人技术已经引起了越来越多在​​医疗领域的兴趣，因为它们在非结构化环境本质安全的相互作用。与此同时，新的程序和技术已经被开发，以减少外科手术的侵入性。微创外科（MIS）已成功地用于腹部干预，但是标准的MIS程序主要是基于刚性或半刚性的工具，限制了临床医生的灵巧。本文提出了一种柔软，高灵巧机械臂的管理信息系统。该机器人是由章鱼臂的生物学功能的启发，并采用模块化方法。每个模块提供相同的功能特性，因此实现高灵活性和多功能性时更模块集成。本文详细描述了设计，制造过程和材料所必需的单个单元，这是由制造CASTIN的发展具体的模具内G型硅。结果包含在弹性筒包括三个弹性气动致动器，使延伸率和单元的全向弯曲。外部编织鞘改善了模块的运动。在每个模块的中心的粒状干扰系机构改变该结构的过程中的任务的刚度。测试表明，该模块能够弯曲达120°和伸长高达66％的初始长度的。该模块产生的47 N A最大的力，其硬度可提高达36％。

的制造中，在协议中所描述的各个阶段，示于图3中 。 为了评价该技术的有效性和最终原型的结果，该模块在不同的工作条件下进行测试。外部设置允许两个致动和模块的刚度的控制。它包括空气压缩机，激活三个阀门。它们被连接到集成在腔室中的含硅管和允许他们的加压。的真空泵连接于管集成在粒状干扰膜为模块刚度控制。阀和真空泵连接到一个电子板，?...

Watch this Scientific Journal Video about Design and Fabrication of an Elastomeric Unit for Soft Modular Robots in Minimally Invasive Surgery at JoVE.com

Design and Fabrication of an Elastomeric Unit for Soft Modular Robots in Minimally Invasive Surgery

This paper describes the design and fabrication of a soft unit for surgical manipulators. The base module includes three flexible fluidic actuators to achieve omnidirectional bending and elongation, and a granular jamming-based mechanism to enable stiffness control. A complete mechanical characterization is also reported.

设计和弹性股软模块化机器人微创手术制造

In recent years, soft robotics technologies have aroused increasing interest in the medical field due to their intrinsically safe interaction in ...

design-fabrication-an-elastomeric-unit-for-soft-modular-robots

Research

JoVE Journal

Bioengineering

8.9K 次观看.  Scuola Superiore Sant'Anna. This paper describes the design and fabrication of a soft unit for surgical manipulators. The base module includes three flexible fluidic actuators to achieve omnidirectional bending and elongation, and a granular jamming-based mechanism to enable stiffness control. A complete mechanical characterization is also reported. 

视频: Design and Fabrication of an Elastomeric Unit for Soft Modular Robots in Minimally Invasive Surgery

Elastomeric PGS Scaffolds in Arterial Tissue Engineering

Cardiovascular disease is one of the leading cause of mortality in the US and especially, coronary artery disease increases with an aging population and increasing obesity1. Currently, bypass surgery using autologous vessels, allografts, and synthetic grafts are known as a commonly used for arterial substitutes2. However, these grafts have limited applications when an inner diameter of arteries is less than 6 mm due to low availability, thrombotic complications, compliance mismatch, and late intimal hyperplasia3,4. To overcome these limitations, tissue engineering has been successfully applied as a promising alternative to develop small-diameter arterial constructs that are nonthrombogenic, robust, and compliant. Several previous studies have developed small-diameter arterial constructs with tri-lamellar structure, excellent mechanical properties and burst pressure comparable to native arteries5,6. While high tensile strength and burst pressure by increasing collagen production from a rigid material or cell sheet scaffold, these constructs still had low elastin production and compliance, which is a major problem to cause graft failure after implantation. Considering these issues, we hypothesized that an elastometric biomaterial combined with mechanical conditioning would provide elasticity and conduct mechanical signals more efficiently to vascular cells, which increase extracellular matrix production and support cellular orientation.
The objective of this report is to introduce a fabrication technique of porous tubular scaffolds and a dynamic mechanical conditioning for applying them to arterial tissue engineering. We used a biodegradable elastomer, poly (glycerol sebacate) (PGS)7 for fabricating porous tubular scaffolds from the salt fusion method. Adult primary baboon smooth muscle cells (SMCs) were seeded on the lumen of scaffolds, which cultured in our designed pulsatile flow bioreactor for 3 weeks. PGS scaffolds had consistent thickness and randomly distributed macro- and micro-pores. Mechanical conditioning from pulsatile flow bioreactor supported SMC orientation and enhanced ECM production in scaffolds. These results suggest that elastomeric scaffolds and mechanical conditioning of bioreactor culture may be a promising method for arterial tissue engineering.

Elastomeric PGS scaffolds with vascular smooth muscle cells cultured in a pulsatile flow bioreactor may lead to promising small-diameter arterial constructs with native ECM production in a relatively short culture period.

弹性PGS的动脉组织工程支架

Cardiovascular disease is one of the leading cause of mortality in the US and especially, coronary artery disease increases with an aging population and ...

科研

生物工程

Polymeric Microneedle Array Fabrication by Photolithography

This manuscript describes the fabrication of polymeric microneedle (MN) arrays by photolithography. It involves a simple mold-free process by using a photomask consisting of embedded micro-lenses. Embedded micro-lenses were found to influence MN geometry (sharpness). Robust MN arrays with tip diameters ranging between 41.5 &#181;m &#177; 8.4 &#181;m and 71.6 &#181;m &#177; 13.7 &#181;m, with two different lengths (1,336 &#181;m &#177; 193 &#181;m and 957 &#181;m &#177; 171 &#181;m) were fabricated. These MN arrays may provide potential applications in delivery of low molecular and macromolecular therapeutic agents through skin.

Here, we present a protocol describing a mold-free fabrication process of the polymeric microneedles by photolithography.

聚合物微针阵列制造用光刻

This manuscript describes the fabrication of polymeric microneedle (MN) arrays by photolithography. It involves a simple mold-free process by using a ...

Rod-based Fabrication of Customizable Soft Robotic Pneumatic Gripper Devices for Delicate Tissue Manipulation

Soft compliant gripping is essential in delicate surgical manipulation for minimizing the risk of tissue grip damage caused by high stress concentrations at the point of contact. It can be achieved by complementing traditional rigid grippers with soft robotic pneumatic gripper devices. This manuscript describes a rod-based approach that combined both 3D-printing and a modified soft lithography technique to fabricate the soft pneumatic gripper. In brief, the pneumatic featureless mold with chamber component is 3D-printed and the rods were used to create the pneumatic channels that connect to the chamber. This protocol eliminates the risk of channels occluding during the sealing process and the need for external air source or related control circuit. The soft gripper consists of a chamber filled with air, and one or more gripper arms with a pneumatic channel in each arm connected to the chamber. The pneumatic channel is positioned close to the outer wall to create different stiffness in the gripper arm. Upon compression of the chamber which generates pressure on the pneumatic channel, the gripper arm will bend inward to form a close grip posture because the outer wall area is more compliant. The soft gripper can be inserted into a 3D-printed handling tool with two different control modes for chamber compression: manual gripper mode with a movable piston, and robotic gripper mode with a linear actuator. The double-arm gripper with two actuatable arms was able to pick up objects of sizes up to 2 mm and yet generate lower compressive forces as compared to elastomer-coated and non-coated rigid grippers. The feasibility of having other designs, such as single-arm or hook gripper, was also demonstrated, which further highlighted the customizability of the soft gripper device, and it's potential to be used in delicate surgical manipulation to reduce the risk of tissue grip damage.

This protocol describes a rod-based approach, combining 3D-printing and soft lithography techniques for fabricating the soft gripper devices. This approach eliminates the need for an external air source by incorporating a chamber component and reduces the chance of occlusion during the sealing process, particularly for miniaturized pneumatic channels.

娇嫩的组织操纵定制的软机器人气动设备手爪基于杆制造

Soft compliant gripping is essential in delicate surgical manipulation for minimizing the risk of tissue grip damage caused by high stress concentrations ...

Automated Robotic Liquid Handling Assembly of Modular DNA Devices

Recent advances in modular DNA assembly techniques have enabled synthetic biologists to test significantly more of the available &#34;design space&#34; represented by &#34;devices&#34; created as combinations of individual genetic components. However, manual assembly of such large numbers of devices is time-intensive, error-prone, and costly. The increasing sophistication and scale of synthetic biology research necessitates an efficient, reproducible way to accommodate large-scale, complex, and high throughput device construction.
Here, a DNA assembly protocol using the Type-IIS restriction endonuclease based Modular Cloning (MoClo) technique is automated on two liquid-handling robotic platforms. Automated liquid-handling robots require careful, often times tedious optimization of pipetting parameters for liquids of different viscosities (e.g. enzymes, DNA, water, buffers), as well as explicit programming to ensure correct aspiration and dispensing of DNA parts and reagents. This makes manual script writing for complex assemblies just as problematic as manual DNA assembly, and necessitates a software tool that can automate script generation. To this end, we have developed a web-based software tool, http://mocloassembly.com, for generating combinatorial DNA device libraries from basic DNA parts uploaded as Genbank files. We provide access to the tool, and an export file from our liquid handler software which includes optimized liquid classes, labware parameters, and deck layout. All DNA parts used are available through Addgene, and their digital maps can be accessed via the Boston University BDC ICE Registry. Together, these elements provide a foundation for other organizations to automate modular cloning experiments and similar protocols.
The automated DNA assembly workflow presented here enables the repeatable, automated, high-throughput production of DNA devices, and reduces the risk of human error arising from repetitive manual pipetting. Sequencing data show the automated DNA assembly reactions generated from this workflow are ~95% correct and require as little as 4% as much hands-on time, compared to manual reaction preparation.

Here, an automated workflow to perform modular DNA &#34;device&#34; assembly using a modular cloning DNA assembly method on liquid-handling robots is presented. The protocol uses an intuitive software tool for generating liquid handler picklists for combinatorial DNA device library generation, which we demonstrate using two liquid handling platforms.

模块化 DNA 设备的自动机器人液体处理组件

Recent advances in modular DNA assembly techniques have enabled synthetic biologists to test significantly more of the available &#34;design space&#34; ...

Biomechanical Characterization of Human Soft Tissues Using Indentation and Tensile Testing

Regenerative medicine aims to engineer materials to replace or restore damaged or diseased organs. The mechanical properties of such materials should mimic the human tissues they are aiming to replace; to provide the required anatomical shape, the materials must be able to sustain the mechanical forces they will experience when implanted at the defect site. Although the mechanical properties of tissue-engineered scaffolds are of great importance, many human tissues that undergo restoration with engineered materials have not been fully biomechanically characterized. Several compressive and tensile protocols are reported for evaluating materials, but with large variability it is difficult to compare results between studies. Further complicating the studies is the often destructive nature of mechanical testing. Whilst an understanding of tissue failure is important, it is also important to have knowledge of the elastic and viscoelastic properties under more physiological loading conditions.
This report aims to provide a minimally destructive protocol to evaluate the compressive and tensile properties of human soft tissues. As examples of this technique, the tensile testing of skin and the compressive testing of cartilage are described. These protocols can also be directly applied to synthetic materials to ensure that the mechanical properties are similar to the native tissue. Protocols to assess the mechanical properties of human native tissue will allow a benchmark by which to create suitable tissue-engineered substitutes.

Tissue biomechanics is important for maintaining cell shape and function and for determining phenotype. This report demonstrates non-destructive mechanical protocols for characterizing elastic and viscoelastic properties of human soft tissues, which can be directly applied to tissue-engineered substrates to allow a close matching of engineered materials to native tissue.

人体软组织的生物力学特性采用压痕和拉伸试验

Regenerative medicine aims to engineer materials to replace or restore damaged or diseased organs. The mechanical properties of such materials should ...

An In Vitro Organ Culture Model of the Murine Intervertebral Disc

Intervertebral disc (IVD) degeneration is a significant contributor to low back pain. The IVD is a fibrocartilaginous joint that serves to transmit and dampen loads in the spine. The IVD consists of a proteoglycan-rich nucleus pulposus (NP) and a collagen-rich annulus fibrosis (AF) sandwiched by cartilaginous end-plates. Together with the adjacent vertebrae, the vertebrae-IVD structure forms a functional spine unit (FSU). These microstructures contain unique cell types as well as unique extracellular matrices. Whole organ culture of the FSU preserves the native extracellular matrix, cell differentiation phenotypes, and cellular-matrix interactions. Thus, organ culture techniques are particularly useful for investigating the complex biological mechanisms of the IVD. Here, we describe a high-throughput approach for culturing whole lumbar mouse FSUs that provides an ideal platform for studying disease mechanisms and therapies for the IVD. Furthermore, we describe several applications that utilize this organ culture method to conduct further studies including contrast-enhanced microCT imaging and three-dimensional high-resolution finite element modeling of the IVD.

An In Vitro Organ Culture Model of the Murine Intervertebral Disc

Whole organ culture of the intervertebral disc (IVD) preserves the native extracellular matrix, cell phenotypes, and cellular-matrix interactions. Here we describe an IVD culture system using mouse lumbar and caudal IVDs in their functional spinal units and several applications utilizing this system.

一个<em&gt;体外</em鼠类的椎间盘&gt;器官培养模型

Intervertebral disc (IVD) degeneration is a significant contributor to low back pain. The IVD is a fibrocartilaginous joint that serves to transmit and ...

A Novel Surgical Technique As a Foundation for In Vivo Partial Liver Engineering in Rat

Organ engineering is a novel strategy to generate liver organ substitutes that can potentially be used in transplantation. Recently, in vivo liver engineering, including in vivo organ decellularization followed by repopulation, has emerged as a promising approach over ex vivo liver engineering. However, postoperative survival was not achieved. The aim of this study is to develop a novel surgical technique of in vivo selective liver lobe perfusion in rats as a prerequisite for in vivo liver engineering. We generate a circuit bypass only through the left lateral lobe. Then, the left lateral lobe is perfused with heparinized saline. The experiment is performed with 4 groups (n = 3 rats per group) based on different perfusion times of 20 min, 2 h, 3 h, and 4 h. Survival, as well as the macroscopically visible change of color and the histologically determined absence of blood cells in the portal triad and the sinusoids, is taken as an indicator for a successful model establishment. After selective perfusion of the left lateral lobe, we observe that the left lateral lobe, indeed, turned from red to faint yellow. In a histological assessment, no blood cells are visible in the branch of the portal vein, the central vein, and the sinusoids. The left lateral lobe turns red after reopening the blocked vessels. 12/12 rats survived the procedure for more than one week. We are the first to report a surgical model for in vivo single liver lobe perfusion with a long survival period of more than one week. In contrast to the previously published report, the most important advantage of the technique presented here is that perfusion of 70% of the liver is maintained throughout the whole procedure. The establishment of this technique provides a foundation for in vivo partial liver engineering in rats, including decellularization and recellularization.

A Novel Surgical Technique As a Foundation for In Vivo Partial Liver Engineering in Rat

We establish a novel surgical technique for an in vivo single liver lobe perfusion model in rat as a prerequisite for further studying in vivo partial liver engineering in the future.

大鼠体内部分肝工程的外科技术基础

Organ engineering is a novel strategy to generate liver organ substitutes that can potentially be used in transplantation. Recently, in vivo liver ...

Bioinspired Soft Robot with Incorporated Microelectrodes

Bioinspired soft robotic systems that mimic living organisms using engineered muscle tissue and biomaterials are revolutionizing the current biorobotics paradigm, especially in biomedical research. Recreating artificial life-like actuation dynamics is crucial for a soft-robotic system. However, the precise control and tuning of actuation behavior still represents one of the main challenges of modern soft robotic systems. This method describes a low-cost, highly scalable, and easy-to-use procedure to fabricate an electrically controllable soft robot with life-like movements that is activated and controlled by the contraction of cardiac muscle tissue on a micropatterned sting ray-like hydrogel scaffold. The use of soft photolithography methods makes it possible to successfully integrate multiple components in the soft robotic system, including micropatterned hydrogel-based scaffolds with carbon nanotubes (CNTs) embedded gelatin methacryloyl (CNT-GelMA), poly(ethylene glycol) diacrylate (PEGDA), flexible gold (Au) microelectrodes, and cardiac muscle tissue. In particular, the hydrogels alignment and micropattern are designed to mimic the muscle and cartilage structure of the sting ray. The electrically conductive CNT-GelMA hydrogel acts as a cell scaffold that improves the maturation and contraction behavior of cardiomyocytes, while the mechanically robust PEGDA hydrogel provides structural cartilage-like support to the whole soft robot. To overcome the hard and brittle nature of metal-based microelectrodes, we designed a serpentine pattern that has high flexibility and can avoid hampering the beating dynamics of cardiomyocytes. The incorporated flexible Au microelectrodes provide electrical stimulation across the soft robot, making it easier to control the contraction behavior of cardiac tissue.

A bioinspired scaffold is fabricated by a soft photolithography technique using mechanically robust and electrically conductive hydrogels. The micropatterned hydrogels provide directional cardiomyocyte cell alignment, resulting in a tailored direction of actuation. Flexible microelectrodes are also integrated into the scaffold to bring electrical controllability for a self-actuating cardiac tissue.

生物灵感软机器人与合并微电极

Bioinspired soft robotic systems that mimic living organisms using engineered muscle tissue and biomaterials are revolutionizing the current biorobotics ...

Simple, Affordable, and Modular Patterning of Cells using DNA

The relative positioning of cells is a key feature of the microenvironment that organizes cell-cell interactions. To study the interactions between cells of the same or different type, micropatterning techniques have proved useful. DNA Programmed Assembly of Cells (DPAC) is a micropatterning technique that targets the adhesion of cells to a substrate or other cells using DNA hybridization. The most basic operations in DPAC begin with decorating cell membranes with lipid-modified oligonucleotides, then flowing them over a substrate that has been patterned with complementary DNA sequences. Cells adhere selectively to the substrate only where they find a complementary DNA sequence. Non-adherent cells are washed away, revealing a pattern of adherent cells. Additional operations include further rounds of cell-substrate or cell-cell adhesion, as well as transferring the patterns formed by DPAC to an embedding hydrogel for long-term culture. Previously, methods for patterning oligonucleotides on surfaces and decorating cells with DNA sequences required specialized equipment and custom DNA synthesis, respectively. We report an updated version of the protocol, utilizing an inexpensive benchtop photolithography setup and commercially available cholesterol modified oligonucleotides (CMOs) deployed using a modular format. CMO-labeled cells adhere with high efficiency to DNA-patterned substrates. This approach can be used to pattern multiple cell types at once with high precision and to create arrays of microtissues embedded within an extracellular matrix. Advantages of this method include its high resolution, ability to embed cells into a three-dimensional microenvironment without disrupting the micropattern, and flexibility in patterning any cell type.

Here we present a protocol to micropattern cells at single-cell resolution using DNA-programmed adhesion. This protocol uses a benchtop photolithography platform to create patterns of DNA oligonucleotides on a glass slide and then labels cell membranes with commercially available complementary oligonucleotides. Hybridization of the oligos results in programmed cell adhesion.

使用DNA对细胞进行简单、经济、模块化的图案化

The relative positioning of cells is a key feature of the microenvironment that organizes cell-cell interactions. To study the interactions between cells ...

Voxel Printing Anatomy: Design and Fabrication of Realistic, Presurgical Planning Models through Bitmap Printing

Most applications of 3-dimensional (3D) printing for presurgical planning have been limited to bony structures and simple morphological descriptions of complex organs due to the fundamental limitations in accuracy, quality, and efficiency of the current modeling paradigm. This has largely ignored the soft tissue critical to most surgical specialties where the interior of an object matters and anatomical boundaries transition gradually. Therefore, the needs of the biomedical industry to replicate human tissue, which displays multiple scales of organization and varying material distributions, necessitate new forms of representation. 
Presented here is a novel technique to create 3D models directly from medical images, which are superior in spatial and contrast resolution to current 3D modeling methods and contain previously unachievable spatial fidelity and soft tissue differentiation. Also presented are empirical measurements of novel, additively manufactured composites that span the gamut of material stiffnesses seen in soft biological tissues from MRI and CT. These unique volumetric design and printing methods allow for deterministic and continuous adjustment of material stiffness and color. This capability enables an entirely new application of additive manufacturing to presurgical planning: mechanical realism. As a natural complement to existing models that provide appearance matching, these new models also allow medical professionals to "feel" the spatially varying material properties of a tissue simulant-a critical addition to a field in which tactile sensation plays a key role.

This method demonstrates a voxel-based 3D printing workflow, which prints directly from medical images with exact spatial fidelity and spatial/contrast resolution. This enables the precise, graduated control of material distributions through morphologically complex, graduated materials correlated to radiodensity without loss or alteration of data.

体素打印剖析：通过位图打印设计和制作逼真的、外科手术前规划模型

Most applications of 3-dimensional (3D) printing for presurgical planning have been limited to bony structures and simple morphological descriptions of ...