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A new flow cell and chemometric protocol for implementing in‐line Raman spectroscopy in chromatography

机译：一种新的流动细胞和化学计量方案，用于在色谱中实施在线拉曼光谱法

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Abstract >On‐line monitoring tools for downstream chromatographic processing (DSP) of biotherapeutics can enable fast actions to correct for disturbances in the upstream, gain process understanding, and eventually lead to process optimization. While UV/Vis spectroscopy is mostly assessing the protein's amino acid composition and the application of Fourier transform infrared spectroscopy is limited due to strong water interactions, Raman spectroscopy is able to assess the secondary and tertiary protein structure without significant water interactions. The aim of this work is to implement the Raman technology in DSP, by designing an in‐line flow cell with a reduced dead volume of 80?μL and a reflector to increase the signal intensity as well as developing a chemometric modeling path. In this context, measurement settings were adjusted and spectra were taken from different chromatographic breakthrough curves of IgG1 in harvest. The resulting models show a small average RMSEP of 0.12?mg/mL, on a broad calibration range from 0 to 2.82?mg/mL IgG1. This work highlights the benefits of model assisted Raman spectroscopy in chromatography with complex backgrounds, lays the fundamentals for in‐line monitoring of IgG1, and enables advanced control strategies. Moreover, the approach might be extended to further critical quality attributes like aggregates or could be transferred to other process steps. </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> > Biotheaptics的下游色谱处理（DSP）的在线监测工具可以在上游，增益过程理解中纠正纠正的快速行动，并最终导致过程优化。虽然UV / Vis光谱母主要评估蛋白质的氨基酸组成和傅里叶变换红外光谱的施加受限受到强水相互作用的限制，拉曼光谱能够评估仲和叔蛋白质结构而没有显着的水相互作用。这项工作的目的是通过设计一条内的流量，减少80μL和反射器的线流量来实现DSP中的拉曼技术，以增加信号强度以及开发化学计量建模路径。在这种情况下，调整测量设置，并从收获中的IgG1的不同色谱突破曲线取出光谱。所得模型显示出0.12×mg / ml的小平均RMSEP，在宽校准范围为0至2.82Ω·mg / ml IgG1。这项工作突出了模型辅助拉曼光谱在色谱色谱中与复杂背景的好处，为IGG1的在线监测奠定了基础，并实现了先进的控制策略。此外，该方法可以扩展到与聚合等进一步的关键质量属性，也可以转移到其他过程步骤。</ 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-15005/'>《Biotechnology Progress》</a> <b style="margin: 0 2px;">|</b><span>2019年第5期</span><b style="margin: 0 2px;">|</b><span>共10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=Feidl Fabian&option=202" target="_blank" rel="nofollow">Feidl Fabian;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Garbellini Simone&option=202" target="_blank" rel="nofollow">Garbellini Simone;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Vogg Sebastian&option=202" target="_blank" rel="nofollow">Vogg Sebastian;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Sokolov Michael&option=202" target="_blank" rel="nofollow">Sokolov Michael;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Souquet Jonathan&option=202" target="_blank" rel="nofollow">Souquet Jonathan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Broly Hervé&option=202" target="_blank" rel="nofollow">Broly Hervé;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Butté Alessandro&option=202" target="_blank" rel="nofollow">Butté Alessandro;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Morbidelli Massimo&option=202" target="_blank" rel="nofollow">Morbidelli Massimo;</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>Institute of Chemical and BioengineeringETH ZurichZurich Switzerland;</p> <p>Institute of Chemical and BioengineeringETH ZurichZurich Switzerland;</p> <p>Institute of Chemical and BioengineeringETH ZurichZurich Switzerland;</p> <p>Institute of Chemical and BioengineeringETH ZurichZurich Switzerland;</p> <p>Biotech Process SciencesMerck Serono S.A.Corsier‐sur‐Vevey Switzerland;</p> <p>Biotech Process SciencesMerck Serono S.A.Corsier‐sur‐Vevey Switzerland;</p> <p>Institute of Chemical and BioengineeringETH ZurichZurich Switzerland;</p> <p>Institute of Chemical and BioengineeringETH ZurichZurich Switzerland;</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/15.html" title="生物科学">生物科学;</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=chromatography&option=203" rel="nofollow">chromatography;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=downstream processing&option=203" rel="nofollow">downstream processing;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=flow cell&option=203" rel="nofollow">flow cell;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=PAT&option=203" rel="nofollow">PAT;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Raman spectroscopy&option=203" rel="nofollow">Raman spectroscopy;</a> </p> <div class="translation"> 机译：色谱法;下游加工;流动细胞;PAT;拉曼光谱; </div> </li> </ul> </div> </div> <div class="literature 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Yan Li</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Guorong Du&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Guorong Du</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Wensheng Cai&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Wensheng Cai</a> <span> <a href="/journal-cn-56200/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 美国分析化学（英文） </a> </span> <span> . 2011</span><span>,第2期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-cn_detail_thesis/0201294528213.html">Role of Raman spectroscopy and surface enhanced Raman spectroscopy in colorectal cancer</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Cerys A Jenkins&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . Cerys A Jenkins</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Paul D Lewis&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Paul D Lewis</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Peter R Dunstan&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Peter R Dunstan</a> <span> <a href="/journal-cn-57405/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 世界胃肠肿瘤学杂志：英文版（电子版） </a> </span> <span> . 2016</span><span>,第5期</span> </span> </div> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/academic-conference-cn_meeting-9639_thesis/020222339402.html">Design and Implementation of XMPP Protocol Based on Single-MCU Platform</a> <b>[C]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Ping WANG&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . Ping WANG</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Jing NING&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Jing NING</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Jingjing WANG&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Jingjing WANG</a> <span> <a href="/conference-cn-9639/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 第三届国际信息技术与管理科学学术研讨会 </a> <span> <span> . 2011</span> </span> </div> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/020316291654.html">Development of surface--enhanced Raman spectroscopy biosensors for ionizing--radiation related biomarkers in biofluids</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Muhammad&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 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