Biotechnology Progress最新文献

RETRACTION: A Novel pH-Responsive Nanoniosomal Emulsion for Sustained Release of Curcumin from a Chitosan-Based Nanocarrier: Emphasis on the Concurrent Improvement of Loading, Sustained Release, and Apoptosis Induction. 摘要：一种新型的ph响应纳米乳剂，用于从壳聚糖为基础的纳米载体中缓释姜黄素：重点是同时改善负载，缓释和诱导细胞凋亡。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-25 DOI: 10.1002/btpr.70038

{"title":"RETRACTION: A Novel pH-Responsive Nanoniosomal Emulsion for Sustained Release of Curcumin from a Chitosan-Based Nanocarrier: Emphasis on the Concurrent Improvement of Loading, Sustained Release, and Apoptosis Induction.","authors":"","doi":"10.1002/btpr.70038","DOIUrl":"https://doi.org/10.1002/btpr.70038","url":null,"abstract":"Retraction: S. Haseli , M. Pourmadadi , A. Samadi , F. Yazdian , M. Abdouss , H. Rashedi , and M. Navaei-Nigjeh , \"A Novel pH-Responsive Nanoniosomal Emulsion for Sustained Release of Curcumin from a Chitosan-Based Nanocarrier: Emphasis on the Concurrent Improvement of Loading, Sustained Release, and Apoptosis Induction,\" Biotechnology Progress 38, no. 5 (2022): e3280, https://doi.org/10.1002/btpr.3280. The above article, published online on 30 June 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, John A. Morgan; the American Institute of Chemical Engineers; the Society for Biological Engineering; and Wiley Periodicals LLC. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate duplication of image panels between this (Figure 4) and another article published by an overlapping group of authors, depicting a different experimental condition. The partial raw data provided by the authors could not address the original concerns, showed inconsistencies with the published results, and ultimately raised additional doubts about the study's overall reliability. Consequently, the editors have lost confidence in the presented data and decided to retract the paper. The authors' institute has been informed of the allegations and the decision to retract but remained unresponsive. The authors disagree with the retraction.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70038"},"PeriodicalIF":2.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A digital shadow of CAR T cell expansion in a perfusion bioreactor: Informing optimal harvest times for autologous cell therapy. 灌注生物反应器中CAR - T细胞扩增的数字阴影：告知自体细胞治疗的最佳收获时间。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-23 DOI: 10.1002/btpr.70045

Joseph R Egan, Núria Marí-Buyé, Elia Vallejo Benítez-Cano, Miquel Costa, Linda Wanika, Michael J Chappell, Ursula Schultz, Jelena Ochs, Manuel Effenberger, David Horna, Qasim Rafiq, Stephen Goldrick

{"title":"A digital shadow of CAR T cell expansion in a perfusion bioreactor: Informing optimal harvest times for autologous cell therapy.","authors":"Joseph R Egan, Núria Marí-Buyé, Elia Vallejo Benítez-Cano, Miquel Costa, Linda Wanika, Michael J Chappell, Ursula Schultz, Jelena Ochs, Manuel Effenberger, David Horna, Qasim Rafiq, Stephen Goldrick","doi":"10.1002/btpr.70045","DOIUrl":"https://doi.org/10.1002/btpr.70045","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy has tremendous potential for the treatment of cancer and other diseases. To manufacture cells of the desired quantity and quality, it is important to expand the CAR T cells ex vivo for an optimal duration. However, identifying the optimal harvest time requires knowledge of the cell concentration during the expansion period. To address this challenge, we have developed a digital shadow of CAR T cell expansion that provides a soft sensor of cell concentration in real-time. Specifically, a novel mechanistic mathematical model of cell growth within a proportional-integral-derivative (PID) controlled perfusion bioreactor has been developed using nonlinear ordinary differential equations. The model is fitted to data generated via bioreactor runs of the Aglaris FACER, in which both donor and patient cells have been expanded in two different media. Off-line data includes the initial and final cell concentrations, and online data includes the glucose and lactate concentrations as well as the perfusion rate. Training the digital shadow utilizes all the off-line and online data for each run. In contrast, real-time testing utilizes only the initial cell concentration and the available online data at the time of model fitting. Real-time testing shows that with at least 2.5 days of online data, the final cell concentration up to 2.5 days later is predicted with a mean relative error of 13% (standard deviation ≈ 6%). Informative real-time predictions of cell concentration via the digital shadow can guide decisions regarding the optimal harvest time of CAR T cells.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70045"},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innovating cell culture process development with deep learning-powered robotic experimentation using the first Industrial Smart Lab Framework. 使用第一个工业智能实验室框架，通过深度学习驱动的机器人实验创新细胞培养过程开发。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-21 DOI: 10.1002/btpr.70051

Shuting Xu, Yanting Huang, Xin Shen, Rongjia Mao, Yiming Song, Wanying Ye, Lijun Wang, Xiaoxiao Tong, Yun Cao, Ruiqiang Sun, Hang Zhou, Weichang Zhou

{"title":"Innovating cell culture process development with deep learning-powered robotic experimentation using the first Industrial Smart Lab Framework.","authors":"Shuting Xu, Yanting Huang, Xin Shen, Rongjia Mao, Yiming Song, Wanying Ye, Lijun Wang, Xiaoxiao Tong, Yun Cao, Ruiqiang Sun, Hang Zhou, Weichang Zhou","doi":"10.1002/btpr.70051","DOIUrl":"10.1002/btpr.70051","url":null,"abstract":"Traditional biologics process development, including antibody and recombinant protein production, typically relies on labor-intensive, iterative cell culture optimization to determine optimal process parameters. To address this inefficiency, we introduced the Industrial Smart Lab Framework for Cell Culture (ISLFCC), an autonomous laboratory that combines deep learning and robotic experimentation to enhance cell culture processes. In this system, robotic arms sample various bioreactors for analysis, and the IoT system transmits these analysis results to decoder-only transformer deep learning models. Based on these analysis results, these models predict future cell states and recommend optimal actions, which are then executed by automation devices through the IoT system, such as adjusting nutrient feeds and temperature shifts. In a comparative case study, our AI-driven process development for three different cell clones resulted in an average titer increase of 26.8% and maintained lactate levels below 1 g/L without rebound in the late phase within just a single batch, surpassing traditional three-stage empirical process development methods. Moreover, our approach has greatly automated cell culture to ensure enhanced reproducibility, data accuracy, adaptability to various cell lines, and seamless scalability across production scales, marking the first implementation of high-throughput automated cell culture in 3 and 15 L bioreactors. By merging AI with robotic execution, ISLFCC provides a transformative framework that accelerates biologics development, representing a paradigm shift towards autonomous, data-driven biomanufacturing.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70051"},"PeriodicalIF":2.5,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of bioreactor process parameters and yeast biomass on Raman spectra. 生物反应器工艺参数和酵母生物量对拉曼光谱的影响。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-16 DOI: 10.1002/btpr.70050

Maarten Klaverdijk, Mehrab Nemati, Marcel Ottens, Marieke E Klijn

{"title":"Impact of bioreactor process parameters and yeast biomass on Raman spectra.","authors":"Maarten Klaverdijk, Mehrab Nemati, Marcel Ottens, Marieke E Klijn","doi":"10.1002/btpr.70050","DOIUrl":"https://doi.org/10.1002/btpr.70050","url":null,"abstract":"In-line Raman spectroscopy combined with chemometric modeling is a valuable process analytical technology (PAT) providing real-time quantitative information on cell culture compounds. Considering that compound quantification through chemometric models depends on pre-processing to maintain consistent changes in intensity at certain wavenumbers, all causes of signal distortion should be well understood to prevent quantification inaccuracies. This work investigated spectral distortion caused by the changing bioreactor parameters temperature, bubble quantity, and medium viscosity. In addition, the isolated spectral contribution of Saccharomyces cerevisiae cells in suspension was also determined. A temperature range from 20 to 40°C resulted in peak shifts up to 0.8 cm-1 to lower wavenumbers, bubbles generated under standard bioreactor operation conditions led to signal attenuation of up to 7.93% reduction in peak intensity, and changes in liquid viscosity resulted in complex peak shift behavior. Isolated biomass concentrations reaching 5 g/L caused up to 44.6% reduction in distinct peak intensity, which was similar to spectra from batch process fermentations. Correcting for the attenuation revealed spectral features of biomass associated with proteins and lipids in the 1000-1500 cm-1 region. However, the spectral contribution of yeast biomass is dominated by signal extinction, which attenuates Raman spectra in a non-linear manner as biomass accumulates. The obtained knowledge on different sources of spectral distortion aids in the development of robust pre-processing and modeling strategies to obtain chemometric models applicable across experimental setups.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70050"},"PeriodicalIF":2.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimization of multi-column chromatography for capture and polishing at high protein load. 高蛋白负载下多柱色谱捕获和抛光的优化。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-09 DOI: 10.1002/btpr.70047

Tiago Castanheira Silva, Madelène Isaksson, Bernt Nilsson, Michel Eppink, Marcel Ottens

{"title":"Optimization of multi-column chromatography for capture and polishing at high protein load.","authors":"Tiago Castanheira Silva, Madelène Isaksson, Bernt Nilsson, Michel Eppink, Marcel Ottens","doi":"10.1002/btpr.70047","DOIUrl":"https://doi.org/10.1002/btpr.70047","url":null,"abstract":"Integrated Continuous Biomanufacturing reduces manufacturing costs while maintaining product quality. A key contributor to high biopharmaceutical costs, specifically monoclonal antibodies (mAbs), is chromatography. Protein A ligands are usually preferred but still expensive in the manufacturing context, and batch chromatography under-utilizes the columns' capacity, compromising productivity to maintain high yields. Continuous chromatography increases columns' Capacity Utilization (CU) without sacrificing yield or productivity. This work presents the in-silico optimization of a 3 Column Periodic Counter-current Chromatography (3C-PCC) of a capture and polishing step for mAbs from a high titer harvest (cmAb = 5 g/L). The 3C-PCC was modeled and Pareto-fronts for continuous and batch modes were used to optimize the 3C-PCC steps varying the flow rate and percentage of breakthrough achieved in the interconnected loading, maximizing Productivity and CU, for varying concentrations of mAb (batch mode concentration of 5 g/L and continuous mode concentration of 2.5, 5, 7.5, and 10 g/L). The shape of the breakthrough curve significantly impacts the optimization of 3C-PCC. The model output was validated for three different protein A ligands using a pure mAb solution. MAb Select SuRe pcc was selected to continuously capture mAb from a high-titer clarified cell culture supernatant (harvest). The product eluates were pooled and used for continuous polishing using a Cation-Exchange resin (CaptoS ImpAct). Experimental results validated model predictions (<7% deviation in the worst case) and a process with two 3C-PCC in sequence was proposed, with a productivity of approximately 100 mg/mL res/h.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70047"},"PeriodicalIF":2.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A simple electrochemical genosensor based on polythiophene acetic acid film for detection of Schistosoma mansoni. 基于聚噻吩乙酸膜的简单电化学基因传感器检测曼氏血吸虫。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-02 DOI: 10.1002/btpr.70048

Maria S M L Oliveira, Raiza P S Lucena, Alberto G Silva-Júnior, Fábio L Melo, Beatriz M Silva, Elainne C S Gomes, César A S Andrade, Maria D L Oliveira

{"title":"A simple electrochemical genosensor based on polythiophene acetic acid film for detection of Schistosoma mansoni.","authors":"Maria S M L Oliveira, Raiza P S Lucena, Alberto G Silva-Júnior, Fábio L Melo, Beatriz M Silva, Elainne C S Gomes, César A S Andrade, Maria D L Oliveira","doi":"10.1002/btpr.70048","DOIUrl":"https://doi.org/10.1002/btpr.70048","url":null,"abstract":"Schistosoma mansoni infection and other neglected diseases pose significant challenges in diagnosis and treatment, particularly in resource-constrained regions. Despite being useful, traditional techniques lack sensitivity, offering frequent false-positive results, highlighting the emergence of innovative tools such as genosensors as a promising solution to this dilemma. In this work, we developed a simple electrochemical biosensor platform based on electropolymerized films of polythiophene acetic acid (PTAA) and a specific DNA probe for the detection of S. mansoni. Electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and atomic force microscopy (AFM) were used to assess the assembly process of the genosensor, as well as to evaluate biodetection assays. The developed biosensor was found to be effective in detecting the target analyte in pure and complex samples such as cerebrospinal fluid, urine, and plasma from infected patients at different concentrations. CV and EIS were extremely useful in the evaluation of the detection process based on the electron kinetics and charge transfer resistance (RCT) in the interface of the biosensor, where the hybridization with the target single-stranded S. mansoni DNA resulted in the variation of these parameters. The genosensor exhibited high sensitivity and selectivity, with a limit of detection of 0.451 pg.μL-1. As genosensors continue to evolve, they promise to revolutionize the field of neglected disease management, providing hope for improved healthcare outcomes worldwide.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70048"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A recurrent neural network for soft sensor development using CHO stable pools in fed-batch process for SARS-CoV-2 spike protein production as a vaccine antigen. 基于CHO稳定池的软传感器开发递归神经网络，用于生产SARS-CoV-2刺突蛋白作为疫苗抗原。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-02 DOI: 10.1002/btpr.70046

Sebastian-Juan Reyes, Robert Voyer, Yves Durocher, Olivier Henry, Phuong Lan Pham

{"title":"A recurrent neural network for soft sensor development using CHO stable pools in fed-batch process for SARS-CoV-2 spike protein production as a vaccine antigen.","authors":"Sebastian-Juan Reyes, Robert Voyer, Yves Durocher, Olivier Henry, Phuong Lan Pham","doi":"10.1002/btpr.70046","DOIUrl":"https://doi.org/10.1002/btpr.70046","url":null,"abstract":"Fed-batch recombinant therapeutic protein (RTP) production processes utilizing Chinese Hamster Ovary (CHO) cells can take a long period of time (>10 days). Within this period, not all critical features may be measured routinely, and in fact, some are only measured once the process is terminated, complicating decision making. As a consequence, utilizing routine current day bioreactor online data to aid in next day predictions is a promising strategy for model predictive control-based feeding strategies. The article details the development of a proposed soft sensor that merges current day bioreactor online data and offline historical sampling data to generate predictions about the next day of the production process. This approach demonstrated the ability to track product titer, cell growth, key metabolites, and cumulative glucose consumption across the 17-day process with low normalized root mean squared error (nRMSE = 0.24) and low normalized mean absolute error (nMAE = 0.18) as well as high linearity with respect to ground data (average R2 = 0.97). It was also demonstrated that the same model architecture could effectively soft sense product titer and metabolic profiles (glucose, lactate, ammonia) without having sampling day's offline data as inputs to the model. This suggests that the proposed model could act as a true soft sensor of hard-to-determine variables such as the trimeric SARS-CoV-2 spike protein that relies on end-of-process measurements to acquire the data (labor-intensive semi-quantitative SDS-PAGE gels or ELISA assay). Instantaneous specific glucose consumption rates were also predicted and showed good agreement with experimental measurements, further offering opportunities for online glucose control.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70046"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3D hepatic spheroids and liver-organ on chip models displayed maintenance of hepatic functions and maturation profile in a long-term culture of the humanized HepaSH cells, a human cell population harvested from chimeric mice. 三维肝球体和肝脏器官芯片模型显示，在长期培养的人源化HepaSH细胞（从嵌合小鼠中收获的人类细胞群）中，肝脏功能和成熟特征得以维持。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-05-31 DOI: 10.1002/btpr.70043

Hanyuan Wang, Carla Meschini, Stéphane Poulain, Soo Hyeon Kim, Hiroshi Arakawa, Yukio Kato, Cecile Legallais, Ulysse Pereira, Yasuyuki Sakai, Eric Leclerc

{"title":"3D hepatic spheroids and liver-organ on chip models displayed maintenance of hepatic functions and maturation profile in a long-term culture of the humanized HepaSH cells, a human cell population harvested from chimeric mice.","authors":"Hanyuan Wang, Carla Meschini, Stéphane Poulain, Soo Hyeon Kim, Hiroshi Arakawa, Yukio Kato, Cecile Legallais, Ulysse Pereira, Yasuyuki Sakai, Eric Leclerc","doi":"10.1002/btpr.70043","DOIUrl":"https://doi.org/10.1002/btpr.70043","url":null,"abstract":"Long-term functional hepatocyte and reproducible cultures are required in pharmaceutical industries to model chronic liver disorders and to perform associated drug testing. In this frame, we have investigated the behavior of the HepaSH cells when cultivated in liver Biochips, in 3D Spheroids, and in Petri for 20 days. HepaSH is a newly developed humanized hepatocyte harvested from chimeric mice. After the cells' harvesting and inoculation, the HepaSH were successfully maintained in cultures in Petri dishes, spheroids, and Biochips for 20 days. The immunostaining confirmed the expressions of albumin, CYP1A2, and CYP3A4 in all conditions. Furthermore, the CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, and CYP3A4 activities were successfully detected in all conditions after 20 days of cultures. Continuous production of albumin and biliary acids was detected in Biochips, Spheroids, and Petri, among which Biochip culture showed the highest albumin secretion level. The RNA sequencing analysis revealed that Biochips and Spheroids cultures enriched hepatic maturation, xenobiotic, lipid, small molecule, steroid, and alcohol metabolisms compared to Petri cultures. Overall, our data demonstrated the feasibility of cultivating the HepaSH cells in Petri, Biochips, and Spheroids for 20 days in the presented protocol, while keeping important liver functions. Biochip and Spheroids cultures show advantages in hepatic maturation, drug metabolism-related gene expression, and albumin secretion (in biochips) compared with conventional Petri culture.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70043"},"PeriodicalIF":2.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Use of LC-MS to characterize host cell protein removal during depth filtration. 使用LC-MS表征深度过滤过程中宿主细胞蛋白的去除。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-05-23 DOI: 10.1002/btpr.70044

Liang-Kai Chu, Ehsan Espah Borujeni, Xuankuo Xu, Andrew L Zydney

{"title":"Use of LC-MS to characterize host cell protein removal during depth filtration.","authors":"Liang-Kai Chu, Ehsan Espah Borujeni, Xuankuo Xu, Andrew L Zydney","doi":"10.1002/btpr.70044","DOIUrl":"https://doi.org/10.1002/btpr.70044","url":null,"abstract":"The removal of host cell proteins (HCPs) is crucial in biopharmaceutical production, as residual impurities can impact product safety and efficacy. While a number of studies have demonstrated that depth filtration can provide significant HCP removal, there is little information on its effectiveness in removing specific HCPs. This study examines the application of liquid chromatography-mass spectrometry (LC-MS) to track HCP removal during depth filtration, providing a detailed analysis of HCP behavior with two commercial depth filters. Our findings reveal significant variability in HCP breakthrough behavior, with transmission patterns showing minimal correlation with either the protein isoelectric point or hydrophobicity, highlighting the unique behavior of individual HCPs. Both the X0SP and X0HC depth filters achieved almost complete removal of Lipoprotein Lipase, and the X0SP filter also effectively removed Lysosomal Acid Lipase (LAL), both known to degrade polysorbate in monoclonal antibody formulations. However, neither filter provided significant removal of Alpha-enolase, Carboxypeptidase D, Glutathione S-transferase, or Phospholipase B-like 2. The X0SP filter showed equal or better removal for 18 out of 20 problematic HCPs, with greater HCP removal seen at lower conductivity. This work provides a detailed framework for understanding and optimizing depth filtration processes, offering insights into the effectiveness of depth filters for removal of problematic HCPs.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70044"},"PeriodicalIF":2.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of LEDs, macronutrients and culture conditions on biomass and artemisinin production using Artemisia annua L. suspension cultures. led、常量营养素和培养条件对黄花蒿悬浮培养生物量和青蒿素产量的影响

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-05-23 DOI: 10.1002/btpr.70041

Wei Heng Lim, Mei Lin Khaw, Oyunbileg Yungeree, Wei Heng Hew, Ankita Rajendra Parab, Bee Lynn Chew, Dwi Kusuma Wahyuni, Sreeramanan Subramaniam

{"title":"Effects of LEDs, macronutrients and culture conditions on biomass and artemisinin production using Artemisia annua L. suspension cultures.","authors":"Wei Heng Lim, Mei Lin Khaw, Oyunbileg Yungeree, Wei Heng Hew, Ankita Rajendra Parab, Bee Lynn Chew, Dwi Kusuma Wahyuni, Sreeramanan Subramaniam","doi":"10.1002/btpr.70041","DOIUrl":"https://doi.org/10.1002/btpr.70041","url":null,"abstract":"Artemisinin is a sesquiterpene lactone extracted from the medicinal plant Artemisia annua L. (sweet wormwood). It has traditionally been utilized in artemisinin-based combination therapies (ACTs) for the malarial parasite, including drug-resistant strains. Natural artemisinin extraction is costly with low yields. Due to its effectiveness, there is a significant rise in the demand for artemisinin production. In vitro cell suspension culture offers a cost-effective and viable technique for artemisinin production. Therefore, this study aimed to optimize a protocol for cell suspension culture of A. annua L. to enhance biomass and artemisinin production. A successful cell suspension culture was initiated from induced callus. The highest cell biomass was obtained in suspension cultures grown with an initial inoculum size of 0.1 g of mixed type cell aggregates, in media with a pH of 6.2 and a rotation speed of 90 rpm. Macronutrient concentrations influenced both biomass and artemisinin content, with optimal biomass achieved at 19 mM KNO3 and 1.56 mM KH2PO4. The absence of these nutrients resulted in the highest artemisinin levels. Different LED wavelengths also significantly influenced biomass and artemisinin production. Red + blue LED increased cell biomass, while the highest artemisinin content was observed under red LED. The upscaling of the culture indicated a variation in biomass yield pattern, but the highest growth index was achieved in the 500 mL Erlenmeyer flask. This study successfully established a cell suspension culture for A. annua L., demonstrating the influence of macronutrients and red LED on biomass and artemisinin production, providing insights for potential large-scale production.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70041"},"PeriodicalIF":2.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0