{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:58:45Z","timestamp":1787885925956,"version":"build-2784847793"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T00:00:00Z","timestamp":1565222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotechnology Progress"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    There is renewed interest in the possibility of using precipitation for initial capture of high\u2010value therapeutic proteins as part of an integrated continuous downstream process. Precipitation is greatly facilitated by the high product titers now achieved in most cell culture processes, in sharp contrast to chromatographic processes whose performance is reduced at high titers. The current study used a combination of reversible cross\u2010linking (zinc chloride, ZnCl\n                    <jats:sub>2<\/jats:sub>\n                    ) and volume exclusion (polyethylene glycol) agents to precipitate a monoclonal antibody product directly from harvested cell culture fluid using a continuous tubular precipitation reactor. The precipitates were then dewatered and continuously washed using tangential flow filtration, with a countercurrent\u2010staged configuration used to reduce the amount of wash buffer required and increase host cell protein removal. Long\u2010term operation was achieved by operating the membrane modules below the critical filtrate flux to avoid fouling. Experimental results demonstrate the feasibility of this fully continuous integrated precipitation process at bench scale, with design calculations used to explore the key factors affecting the performance of this system for initial antibody capture.\n                  <\/jats:p>","DOI":"10.1002\/btpr.2886","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T03:03:17Z","timestamp":1564023797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Continuous precipitation for monoclonal antibody capture using countercurrent washing by microfiltration"],"prefix":"10.1002","volume":"35","author":[{"given":"Zhao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering The Pennsylvania State University  Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Carnegie Mellon University  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Coffman","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc.  Fremont California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Przybycien","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Carnegie Mellon University  Pittsburgh Pennsylvania"},{"name":"Department of Chemical &amp; Biological Engineering Rensselaer Polytechnic Institute  Troy New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1865-9156","authenticated-orcid":false,"given":"Andrew L.","family":"Zydney","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering The Pennsylvania State University  Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01207a034"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119013020.ch27"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R200007-MCP200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2006.09.026"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470444894.ch4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.436"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2014.07.436"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2014.07.012"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2015.11.032"},{"key":"e_1_2_7_11_1","volume-title":"Talk presented at AIChE National Meeting","author":"Jaquez OA","year":"2010"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26922"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA15453C"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2016.04.010"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2545"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.memsci.2006.04.014"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26441"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2015.02.026"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26497"}],"container-title":["Biotechnology Progress"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btpr.2886","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/btpr.2886","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btpr.2886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T12:10:59Z","timestamp":1761567059000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btpr.2886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,8]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1002\/btpr.2886"],"URL":"https:\/\/doi.org\/10.1002\/btpr.2886","archive":["Portico"],"relation":{},"ISSN":["8756-7938","1520-6033"],"issn-type":[{"value":"8756-7938","type":"print"},{"value":"1520-6033","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,8]]},"assertion":[{"value":"2019-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2886"}}