{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:43:23Z","timestamp":1788018203608,"version":"build-2784847793"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T00:00:00Z","timestamp":1600473600000},"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":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spectroscopy techniques are being implemented within the biopharmaceutical industry due to their non\u2010destructive ability to measure multiple analytes simultaneously, however, minimal work has been applied focussing on their application at small scale. Miniature bioreactor systems are being applied across the industry for cell line development as they offer a high\u2010throughput solution for screening and process optimization. The application of small volume, high\u2010throughput, automated analyses to miniature bioreactors has the potential to significantly augment the type and quality of data from these systems and enhance alignment with large\u2010scale bioreactors. Here, we present an evaluation of 1. a prototype that fully integrates spectroscopy to a miniature bioreactor system (ambr\u00ae15, Sartorius Stedim Biotech) enabling automated Raman spectra acquisition, 2. In 50\u2009L single\u2010use bioreactor bag (SUB) prototype with an integrated spectral window. OPLS models were developed demonstrating good accuracy for multiple analytes at both scales. Furthermore, the 50\u2009L SUB prototype enabled on\u2010line monitoring without the need for sterilization of the probe prior to use and minimal light interference was observed. We also demonstrate the ability to build robust models due to induced changes that are hard and costly to perform at large scale and the potential of transferring these models across the scales. The implementation of this technology enables integration of spectroscopy at the small scale for better process understanding and generation of robust models over a large design space while facilitating model transfer throughout the scales enabling continuity throughout process development and utilization and transfer of ever\u2010increasing data generation from development to manufacturing.<\/jats:p>","DOI":"10.1002\/btpr.3074","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T09:33:50Z","timestamp":1598866430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Spectroscopy integration to miniature bioreactors and large scale production bioreactors\u2013Increasing current capabilities and model transfer"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3678-2791","authenticated-orcid":false,"given":"Ruth C.","family":"Rowland\u2010Jones","sequence":"first","affiliation":[{"name":"Biopharm Process Research, Biopharm Product Development and Supply GlaxoSmithKline R&amp;D  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0401-7470","authenticated-orcid":false,"given":"Alexander","family":"Graf","sequence":"additional","affiliation":[{"name":"Product Development, PAT Corporate Research, Bioprocessing Sartorius Stedim Biotech GmbH  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus","family":"Woodhams","sequence":"additional","affiliation":[{"name":"Hardware Development The Automation Partnership (Cambridge) Limited  Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4299-3667","authenticated-orcid":false,"given":"Paloma","family":"Diaz\u2010Fernandez","sequence":"additional","affiliation":[{"name":"Biopharm Process Research, Biopharm Product Development and Supply GlaxoSmithKline R&amp;D  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Warr","sequence":"additional","affiliation":[{"name":"Biopharm Process Research, Biopharm Product Development and Supply GlaxoSmithKline R&amp;D  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Soeldner","sequence":"additional","affiliation":[{"name":"Product Development, PAT Corporate Research, Bioprocessing Sartorius Stedim Biotech GmbH  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Finka","sequence":"additional","affiliation":[{"name":"Biopharm Process Research, Biopharm Product Development and Supply GlaxoSmithKline R&amp;D  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Hoehse","sequence":"additional","affiliation":[{"name":"Product Development, PAT Corporate Research, Bioprocessing Sartorius Stedim Biotech GmbH  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,19]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Mordor Intelligence LLP. Biopharmaceuticals Market \u2010 Growth Trends and Forecast (2019\u20132024) 2019."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2019.03.015"},{"issue":"1","key":"e_1_2_7_4_1","first-page":"10","article-title":"Perspectives on monoclonal antibody therapy as potential therapeutic intervention for coronavirus disease\u201019 (COVID\u201019)","volume":"38","author":"Shanmugaraj B","year":"2020","journal-title":"Asian Pac J Allergy Immunol"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2584"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700461"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2832"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2019.107307"},{"key":"e_1_2_7_9_1","unstructured":"U.S. Department of Health and Human Services. 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H.C.;Boelens H. F.M.Baseline correction with asymmetric least squares smoothing 2005."},{"key":"e_1_2_7_22_1","volume-title":"Multi\u2010 and Megavariate Data Analysis. Basic Principles And Applications, Third Revised Edition; Umetrics Academy \u2010 Training in Multivariate Technology","author":"Eriksson L","year":"2013"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2459"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.23023"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.03.100149.002103"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/07388551.2015.1084266"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-015-9889-2"},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/jrs.5597","article-title":"Lock\u2010in detection in Raman spectroscopy with charge\u2010shifting CCD for suppression of fast varying backgrounds","volume":"49","author":"Sowoidnich K","year":"2019","journal-title":"J. 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