Assuring Clonality on the Beacon Digital Cell Line Development Platform

Le Kim; Tan Christopher; Le Huong; Tat Jasmine; Zasadzinska Ewelina; Diep Jonathan; Zastrow Ryan; Chen Chun; Stevens Jennitte

摘要

Abstract >During biomanufacturing cell lines development, the generation and screening for single‐cell derived subclones using methods that enable assurance of clonal derivation can be resource‐ and time‐intensive. High‐throughput miniaturization, automation, and analytic strategies are often employed to reduce such bottlenecks. The Beacon platform from Berkeley Lights offers a strategy to eliminate these limitations through culturing, manipulating, and characterizing cells on custom nanofluidic chips via software‐controlled operations. However, explicit demonstration of this technology to provide high assurance of a single cell progenitor has not been reported. Here, a methodology that utilizes the Beacon instrument to ensure high levels of clonality is described. It is demonstrated that the Beacon platform can efficiently generate production cell lines with a superior clonality data package, detailed tracking, and minimal resources. A stringent in‐process quality control strategy is established to enable rapid verification of clonal origin, and the workflow is validated using representative Chinese hamster ovary‐derived cell lines stably expressing either green or red fluorescence protein. Under these conditions, a 99% assurance of clonal origin is achieved, which is comparable to existing imaging‐coupled fluorescence‐activated cell sorting seeding methods. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> >在生物制造细胞系中，使用方法的单细胞衍生子句的发电和筛选能够保证克隆衍生的方法可以是资源和时间密集的。通常采用高吞吐量小型化，自动化和分析策略来减少这种瓶颈。来自Berkeley Lights的信标平台通过软件控制操作在定制纳米流体芯片上培养，操纵和表征细胞来消除这些限制的策略。然而，尚未报告该技术的显式证明，以提供高度保证单个细胞祖细胞祖细胞。这里，描述了利用信标仪器以确保高水平克隆性的方法。据证明信标平台可以有效地产生具有优越的克隆性数据包，详细跟踪和最小资源的生产细胞系。建立了严格的过程质量控制策略，以实现克隆源的快速验证，并且使用稳定表达绿色或红色荧光蛋白的代表性汉仓卵巢衍生细胞系来验证工作流程。在这些条件下，实现了A＆GT;实现了99％的克隆起源的保证，其与现有的成像偶联荧光激活细胞分选方法相当。</ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-15025/'>《Biotechnology Journal: Healthcare,Nutrition,Technology》</a> <b style="margin: 0 2px;">|</b><span>2020年第1期</span><b style="margin: 0 2px;">|</b><span>共7页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Le Kim&option=202" target="_blank" rel="nofollow">Le Kim;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Tan Christopher&option=202" target="_blank" rel="nofollow">Tan Christopher;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Le Huong&option=202" target="_blank" rel="nofollow">Le Huong;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Tat Jasmine&option=202" target="_blank" rel="nofollow">Tat Jasmine;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zasadzinska Ewelina&option=202" target="_blank" rel="nofollow">Zasadzinska Ewelina;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Diep Jonathan&option=202" target="_blank" rel="nofollow">Diep Jonathan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zastrow Ryan&option=202" target="_blank" rel="nofollow">Zastrow Ryan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chen Chun&option=202" target="_blank" rel="nofollow">Chen Chun;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Stevens Jennitte&option=202" target="_blank" rel="nofollow">Stevens Jennitte;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> <p>Drug Substance TechnologiesAmgen Inc.One Amgen Center Drive Thousand Oaks CA 91320 USA;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/180.html" title="生物工程学（生物技术）">生物工程学（生物技术）;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Berkeley Lights&option=203" rel="nofollow">Berkeley Lights;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cell line development&option=203" rel="nofollow">cell line development;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chinese hamster ovary cells&option=203" rel="nofollow">Chinese hamster ovary cells;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=clonality assurance&option=203" rel="nofollow">clonality assurance;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=digital cell culture&option=203" rel="nofollow">digital cell culture;</a> </p> <div class="translation"> 机译：伯克利灯;细胞系发展;中国仓鼠卵巢细胞;克隆性保证;数字细胞文化; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704021883187.html">Assuring Clonality on the Beacon Digital Cell Line Development Platform</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Le Kim&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Le Kim,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Tan Christopher&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Tan Christopher,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Le Huong&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Le Huong,</a> <a href="/journal-foreign-15025/" target="_blank" rel="nofollow" class="tuijian_authcolor">Biotechnology Journal: Healthcare,Nutrition,Technology .</a> <span>2020</span><span>,第1期</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：确保信标数字单元线开发平台上的克隆性</span> </p> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704025205638.html">Development of automated platforms for high-throughput screening of clonal viral packaging and producer cell lines</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Pollack S.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Pollack S.,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Greenwood C.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Greenwood C.,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Burridge M.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Burridge M.,</a> <a href="/journal-foreign-32939/" target="_blank" rel="nofollow" class="tuijian_authcolor">Human gene therapy .</a> <span>2019</span><span>,第11期</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：克隆病毒包装和生产者细胞高通量筛选自动化平台的开发</span> </p> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/070401084673.html">Development of a High-Throughput Screening Platform for DNA 3'-Phosphatases and Their Inhibitors Based on a Universal Molecular Beacon and Quantitative Real-time PCR</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chen Song&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Chen Song,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chen Zhang&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Chen Zhang,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Mei-Ping Zhao&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Mei-Ping Zhao </a> <a href="/journal-foreign-16161/" target="_blank" rel="nofollow" class="tuijian_authcolor">Chemistry, an Asian journal .</a> <span>2010</span><span>,第5期</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：基于通用分子信标和定量实时PCR的DNA 3'-磷酸酶及其抑制剂高通量筛选平台的开发</span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/academic-conference-foreign_meeting-289074_thesis/0705016409516.html">Development of RNA FISH targeting living cells using photo-cross-linkable beacon probe</a> <b>[C]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Misaki Hashimoto&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Misaki Hashimoto,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shigetaka Nakamura&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Shigetaka Nakamura,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Kenzo Fujimoto&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Kenzo Fujimoto </a> <a href="/conference-foreign-289074/" target="_blank" rel="nofollow" class="tuijian_authcolor">日本化学会春季年会講演予稿集 .</a> <span>2018</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：使用光交联符号探测器靶向活细胞的RNA鱼</span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-degree-foreign_mphd_thesis/02061185660.html">Development of Cell Culture Processes on Digital Microfluidic Platforms.</a> <b>[D] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Au, Sam H.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Au, Sam H. </a> <span>2013</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：在数字微流控平台上开发细胞培养过程。</span> </p> </li> <li> <div> <b>6. </b><a class="enjiyixqcontent" href="/academic-journal-foreign-pmc_detail_thesis/040007174109.html">The digital biomarker discovery pipeline: An open-source software platform for the development of digital biomarkers using mHealth and wearables data</a> <b>[O] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Brinnae Bent&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Brinnae Bent,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Ke Wang&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Ke Wang,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Emilia Grzesiak&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Emilia Grzesiak,</a> <span>2021</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：数字生物标志物发现管道：使用MHECHEATH和可穿戴物数据开发数字生物标志物的开源软件平台</span> </p> </li> <li> <div> <b>7. </b><a class="enjiyixqcontent" href="/open-access_resources_thesis/01000130924119.html">Assuring Clonality on the Beacon Digital Cell Line Development Platform</a> <b>[O] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Kim Le&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Kim Le,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Christopher Tan&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Christopher Tan,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Huong Le&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Huong Le,</a> <span>2019</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：确保信标数字单元线开发平台上的克隆性</span> </p> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_voice-screen-world_thesis/0201259907306.html">江西省全力推进有线电视数字化整体转换统一思想明确任务落实责任确保如期完成全省有线电视数字化工作</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=孙刚&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 孙刚</a> <span> <a href="/journal-cn-2499/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 声屏世界 </a> </span> <span> . 2011</span><span>,第002期</span> </span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/academic-journal-cn_jiangsu-education_thesis/0201219867665.html">顺应思维单元整合深度学习r——关于苏教版四上"垂线与平行线"单元学历案的实践与思考</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=雍建皖&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 雍建皖</a> <span> <a href="/journal-cn-3280/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 江苏教育（小学教学版） </a> </span> <span> . 2018</span><span>,第002期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-cn_digital-communication-world_thesis/0201237092261.html">立足新起点,推动新发展,开创有线电视数字化工作新局面——国家广播电影电视总局张海涛副局长2006年5月17日在"全国有线电视数字化推进工作现场会"上的讲话摘要</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . </a> <span> <a href="/journal-cn-8773/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 数字通信世界 </a> </span> <span> . 2006</span><span>,第008期</span> </span> </div> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/academic-journal-cn_digital-communication-world_thesis/0201297911807.html">把城市有线电视数字化不断推向深入——国家广播电影电视总局王太华局长2006年5月17日在“全国有线电视数字化推进工作现场会”上的讲话摘要</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . </a> <span> <a href="/journal-cn-8773/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 数字通信世界 </a> </span> <span> . 2006</span><span>,第8期</span> </span> </div> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-journal-cn_world-network-multimedia_thesis/0201227996036.html">不对称数字用户线的发展,应用及关键技术（上）：不对称数字用户线概述</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=毕厚杰&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 毕厚杰</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=曹雪虹&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,曹雪虹</a> <span> <a href="/journal-cn-25611/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 世界网络与多媒体 </a> </span> <span> . 1998</span><span>,第009期</span> </span> </div> </li> <li> <div> <b>6. </b><a class="enjiyixqcontent" href="/academic-conference-cn_meeting-4827_thesis/020221173214.html">卫星信标信号频谱在数字接收机跟踪性能分析上的应用</a> <b>[C]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李兵&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 李兵</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=周启荣&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,周启荣</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=周阳辉&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,周阳辉</a> <span> <a href="/conference-cn-4827/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 第二十八届全国通信与信息技术学术年会 </a> <span> <span> . 2013</span> </span> </div> </li> <li> <div> <b>7. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/020313486173.html">基于PXA270的ARM开发平台原理图设计——并在其上实现移动数字电视的接收</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=崔恒&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 崔恒</a> <span> . 2010</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06120201259043.html">多普勒甚高频全向信标的全频段数字监视器单元</a> <b>[P]</b> . <span> 中国专利： CN201259539Y </span> <span> . 2009-06-17</span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06120101173830.html">存储器单元，具有个别地包括电容器及晶体管的存储器单元且包括多行存取线及多列数字线的阵列，2T-1C存储器单元，及形成具有电容器及上面的存取晶体管的阵列的方法</a> <b>[P]</b> . <span> 中国专利： CN110235245A </span> <span> . 2019-09-13</span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130444680111.html">Nucleic acid sequence, amino acid sequence, replicative cloning vector, isolated host cell expression vector, methods for testing a substance as a therapeutic agent for bone modulation in a host to identify a molecule and a candidate protein involved in bone modulation, to test for hbm activity, for pharmaceutical development to treat bone development disorders, to treat a bone development disorder in an animal, to alter bone development in a host, to treat osteoporosis, to evaluate diagnosis for a genetic predisposition to a bone development disorder, to identify a genetic predisposition to bone development disorders, to express hbm protein in bone tissue, to amplify a nucleotide polymorphism, to identify a regulatory element of an hbm gene, and to modulate bone density and in one patient, diagnostic assay for bone development disorders, bacterial artificial chromosome, isolated nucleic acid segment, nucleic acid, and polypeptide.</a> <b>[P]</b> . <span> 外国专利：  BR0017197A </span> <span> . 2003-01-14</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：核酸序列，氨基酸序列，复制性克隆载体，分离的宿主细胞表达载体，在宿主中测试作为骨调节治疗剂的物质的方法以鉴定参与骨调节的分子和候选蛋白以测试hbm活性，用于药物开发以治疗骨骼发育异常，治疗动物骨骼发育异常，改变宿主的骨骼发育，治疗骨质疏松症，评估对骨骼发育异常的遗传易感性诊断，鉴定遗传易患骨发育障碍，在骨组织中表达hbm蛋白，扩增核苷酸多态性，鉴定hbm基因的调节元件并调节骨密度，并且在一名患者中进行骨发育障碍的诊断测定，细菌人工染色体，分离的核酸片段，核酸和多肽。 </span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/patent-detail/06130452688695.html">Method of modifying the composition and / or development of cells, tissues or organs in vivo, a cloning vector used in the method, plantao part of Plant transformed with this vector,Host Body comprising Said vector, transformed cell with that Agency.</a> <b>[P]</b> . <span> 外国专利：  AR006937A1 </span> <span> . 1999-09-29</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：体内改变细胞，组织或器官组成和/或发育的方法，该方法中使用的克隆载体，用该载体转化的植物的植物部分，包含所述载体的宿主体，用该试剂转化的细胞。 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130411491200.html">SYSTEM OF PROVIDING SERVICE PLATFORM FOR DEVELOPMENT OF BEACON BASED APPICATION AND METHOD THEREOF</a> <b>[P]</b> . <span> 外国专利：  KR20160065782A </span> <span> . 2016-06-09</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：基于beacon的应用程序开发服务平台的提供系统及其方法 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> </div> <div id="thesis_get_original1" class="downloadBth" style="bottom: 19px;z-index: 999;" onclick="ywcd('0704021883187','4',7,2,1,'',this,24)" class="delivery" prompt="010401" title="通过人工服务将文献原文发送至邮箱" >获取原文</div> <div class="journalsub-pop-up" style="display: none"> <div class="journal-sub"> <h2>期刊订阅</h2> <img src="https://cdn.zhangqiaokeyan.com/img/loginclose.png" alt="关闭" onclick="$('.journalsub-pop-up').hide()"> <p class="pardon">抱歉，该期刊暂不可订阅，敬请期待！</p> <p class="current">目前支持订阅全部北京大学中文核心（2020）期刊目录。</p> <div style="display: flex;margin-top: 69px;justify-content: space-between;"> <div class="no-sub" onclick="$('.journalsub-pop-up').hide()">暂不订阅</div> <div class="other-sub" onclick="continueSub('from=pc-detail')">继续订阅其他期刊</div> </div> </div> </div> <div class="right_btn"> <ul> <li class="gouwuche">  </li> <li class="yijian"> <a href="javascript:void(0);" onclick="link_analysis('/mycenter/auth/complaint.html',this)" title="意见反馈">意见反馈</a> </li> <li class="top"> <a href="javascript:scrollTo(0,0);" title="回到顶部">回到顶部</a> </li> <li class="shouye"> <a href="/" title="首页">回到首页</a> </li> </ul> </div> <div class="xllindexfooter"> <div class="xllindexfootercenter"> <div class="xllindexfooterleft left" > <div class="xllindexfooterleftli"> <ul> <li><a href="/about.html" title="关于掌桥">关于掌桥</a></li> <li><a href="/help/helpmap.html" title="资源导航">资源导航</a></li> <li><a href="/help/helpguide.html" title="新手指南">新手指南</a></li> <li><a href="/help/helpcenter.html" title="常见问题">常见问题</a></li> <li><a href="/sitemap.html" title="网站地图">网站地图</a></li> <li><a href="/help/helpcenter.html?type=9" title="版权声明">版权声明</a></li> </ul> </div> <div class="xllindexfooterleft"> <p class="xllindexfooterlefteamil">客服邮箱：kefu@zhangqiaokeyan.com</p> <div class="xllindexfooterlefttcp"> <div class="xllindexfooterpoliceiimg"></div> <div class="xllindexfooterpoliceispan"> <span>京公网安备：11010802029741号 </span> <span>ICP备案号：<a href="https://beian.miit.gov.cn" rel="nofollow" target="_blank" title="ICP备案号">京ICP备15016152号-6</a></span> <span>六维联合信息科技 (北京) 有限公司©版权所有</span> </div> </div> </div> </div> <div class="xllindexfooterright left"> <ul> <li> <p style="font-weight: bold;">客服微信</p> <div></div> </li> <li> <p style="font-weight: bold;">服务号</p> <div></div> </li> </ul> </div> </div> </div> <span id="0704021883187down" data-source="7," data-out-id="gUYRitlvdzu/ahdqX7hfyviN7LMwkGTdnlyDPHMiNmGmlAdoe4BcoapFjQOrtwoB," data-f-source-id="7" data-title="Assuring Clonality on the Beacon Digital Cell Line Development Platform" data-price="20" data-site-name="" data-transnum="24" style="display:none;"></span> <input type="hidden" value="4" id="sourcetype"> <input type="hidden" value="15025" id="journalid"> <input type="hidden" value="4" id="inyn_provide_service_level"> <input type="hidden" value="https://cdn.zhangqiaokeyan.com" id="imgcdn"> <input type="hidden" value="1" id="isdeatail"> <input type="hidden" value="" id="syyn_indexed_database"> <input type="hidden" value="" id="servicetype"> <input type="hidden" id="pagename" value="Assuring Clonality on the Beacon Digital Cell Line Development Platform"/> <input type="hidden" value="thesis_get_original" id="pageIdentification"> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/jquery-1.12.4.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/lwlh_ajax.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/zq.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/common.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/jquery.cookie.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/top.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/tip.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/login.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/down.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/search.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/newmail.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/searchtype.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/user/regist.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/zxs_solor/detail.js?v=5.7.8"></script> <script type="text/javascript" src="https://www.zhangqiaokeyan.com/statistics/static/pagecollection.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/tj.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/sse.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/pushbaidu.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/common/history.js"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/util/cookie.js?v=5.7.8"></script> <script type="text/javascript" src="https://cdn.zhangqiaokeyan.com/js/weipu/weipu.js?v=5.7.8"></script> </body> <script> function kefu(customization) { var from = GetQueryString("from"); if (from == null || from == "") { from = "other"; } var url = getWxWorkQrCode(55, from, customization); if (url == "" || typeof url == 'undefined') { url = "https://wework.qpic.cn/wwpic/994838_0LUTS-VqR0quT1N_1675665967/0"; } tipDocGuidance(url, '人工辅助获取外文期刊材料'); } $(function(){ var weiPuStatus = getCookie('WeiPuStatus'); if(weiPuStatus){ tipWeiPuStatus(weiPuStatus); delCookie('WeiPuStatus'); } getFacetKeywordVoInId(); var sourcetype = $("#sourcetype").val(); var inyn_provide_service_level = $("#inyn_provide_service_level").val(); if((sourcetype ==1||sourcetype==4)&&inyn_provide_service_level!=4){ getJournal(); } }) </script> </html>