BIOTECHNOLOGY PROGRESS生物技术进展
BIOTECHNOLOGY PROGRESS(英文缩写 BIOTECHNOL PROGR),ISSN 8756-7938,eISSN 1520-6033,中文译名:生物技术进展 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 2.909 | Q3 |
| 2022 | 2.900 | Q3 |
| 2023 | 2.500 | Q3 |
| 2024 | 2.500 | Q3 |
| 2025 | 2.800 | Q3 |
BIOTECHNOLOGY PROGRESS 最新收录文献
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1. BioOps: Enabling MLOps for scalable and flexible model-centric process control in biopharmaceutical development.
PMID:日期:2026-09-15The deployment of advanced modeling and machine learning in biopharmaceutical process control has been limited by legacy fragmented automation infrastructure and a lack of model lifecycle governance. We present BioOps, a modular automation framework for biopharmaceutical advanced process control (APC). The framework incorporates established Machine Learning Operations (MLOps) principles, including version-controlled model registries, containerized deployment, and continuous integration/continuous delivery (CI/CD) pipelines. BioOps explicitly decouples model development from model execution within the control architecture. This decoupling enables process scientists to deploy, test, and iteratively refine mathematical models and control strategies in a flexible manner. These workflows can be applied across heterogeneous bioreactor platforms and are executed entirely in-house, without reliance on vendor-specific solutions or custom system integration. In addition, BioOps embeds traceability, auditability, and model lifecycle management directly into the control stack. As a result, the framework aligns with regulatory expectations while continuing to support agile, in-house experimentation and development. Case studies across a geographically distributed set of bioreactors demonstrate BioOps' versatility in PAT-driven feedback control, hybrid model-based nutrient and glucose feeding, adaptive phase transitions, and cross-scale deployment. By operationalizing model-centric control through an MLOps-inspired architecture, BioOps provides a practical foundation for scalable, reproducible, and future-ready biomanufacturing.
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2. Evaluation of media intensification strategies in perfusion.
PMID:日期:2026-09-10Upstream continuous manufacturing of biologic therapeutics has been an attractive method to address growing demand. However, maintaining high cell densities (>100 million cells/mL) for long periods of time (>25 days) requires large amounts of media, complicating logistics and presenting a roadblock to increased adoption. To reduce volumetric media use, intensified media recipes have been developed. This study evaluates two such recipes to reduce perfusion rate by up to 30%: the first, a concentrated media formulation to increase nutritional depth, and the second, a commercial perfusion rate reducing supplement. We observe how the cell process, productivity, and product quality are impacted. Direct media intensification stalls cell growth by increasing osmolality, ultimately decreasing cell viability. Meanwhile, media with the perfusion rate reducing supplement maintains cell viability and productivity and has no significant impact on product quality compared to the control. We demonstrated the generalizability of the perfusion rate reducing supplement by testing with a different media and cell clone and observed similar results. Cell cycle analysis demonstrated that both intensified media strategies successfully stall cells in the G0/G1 phase, but the perfusion rate reducing supplement more effectively arrests cell proliferation, suggesting a larger shift from growth-driven cells in glycolysis to production-driven cells in oxidative metabolism, and likely contributing to its superior performance. These findings demonstrate important considerations in media intensification and introduce the perfusion rate reducing supplement as a viable media supplement to reduce volumetric media consumption while maintaining process performance.
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3. Small scale purification and biophysical characterization of haptoglobin derived from human Cohn fraction IV.
PMID:日期:2026-09-06Haptoglobin (Hp) is a polymorphic acute phase α-2 glycoprotein found in plasma that plays a critical role in binding, neutralizing, and removing cell-free hemoglobin (Hb) from the circulation. Under clinical conditions characterized by high levels of hemolysis, such as in patients with sickle cell disease (SCD), large quantities of cell-free Hb are released from lysed red blood cells (RBCs) into the circulation and bind to Hp. This interaction reduces the plasma Hp concentration below basal levels and diminishes its Hb-binding capacity. Therefore, plasma-derived Hp has the potential to be used therapeutically to scavenge, neutralize, and remove excess cell-free Hb from the blood, thus preventing Hb-mediated toxicity. This provides strong motivation to purify Hp at high purity using sustainable sources, such as waste plasma fractions from the Cohn plasma fractionation process used to produce human serum albumin from pooled plasma. Starting from human Cohn fraction IV, we first enriched an Hp-rich fraction using tangential flow filtration (TFF), which was then used as the starting material for purification. Hp was subsequently purified from this fraction using hydrophobic interaction chromatography (HIC) to homogeneity. The final Hp purity reached 98% by SDS-PAGE densitometry and 87% by trypsin digest LC-MS/MS analysis. The purified Hp was further characterized to determine its molecular weight, secondary structure, Hb-binding capacity, and binding kinetics using biophysical techniques including MALDI-TOF, circular dichroism, size exclusion HPLC, and UV-visible stopped-flow spectroscopy. More importantly, the simplicity and efficiency of the TFF-HIC workflow demonstrated strong potential for scalable Hp production.
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4. Bone marrow-like viscosity affects imatinib resistance in chronic myeloid leukemia.
PMID:日期:2026-08-22Chronic myeloid leukemia (CML), one type of blood cancer, is a clonal myeloproliferative disorder of hematopoietic stem cells that originated from bone marrow (BM). Imatinib (IM) resistance in CML treatment has been frequently reported, which mainly results from the complex microenvironment of BM. BM is a viscous tissue where cells are mechanically responsive to both the stiffness of matrices and the viscosity of surrounding fluid. Although the effect of stiffness on CML drug resistance has been revealed, the role of BM viscosity on IM resistance in CML is unclear. In this study, a BM-like viscous culture medium was prepared to investigate the effect of microenvironmental viscosity on IM resistance in CML cells. The culture media with viscosity ranging from 47.6 to 634.9 cP were prepared to establish viscosity-controlled culture media covering the reported physiological range of bone marrow and extending into an exploratory higher-viscosity condition. CML cells were suspended and cultured in the viscous culture media added or without addition of IM for 48 or 72 h. Cell viability decreased with IM concentration but increased with microenvironmental viscosity. The results suggested that increased microenvironmental viscosity reduced the sensitivity of CML cells to IM. The possible mechanism might involve the upregulated expression of IM resistance-related genes, reduced apoptosis rates, and altered expression patterns of the BCR::ABL1 gene.
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5. Lipid droplet profiling during neutrophil differentiation by stimulated Raman scattering microscopy.
PMID:日期:2026-08-19Lipid droplets (LDs) are dynamic organelles that serve as metabolic hubs and emerging regulators of immune cell fate. Although LDs have been implicated in immune regulation, how LD metabolism is remodeled during neutrophil differentiation and how stage-specific LD dynamics shape mature neutrophil function remain poorly defined. Here, we profiled LD dynamics during neutrophil development and evaluated their role in innate immune function. Using stimulated Raman scattering (SRS) microscopy, we performed label-free, quantitative mapping of LD accumulation in two complementary differentiation systems: murine Hoxb8 myeloid progenitors and human pluripotent stem cell (hPSC)-derived neutrophils. To define metabolic requirements, we pharmacologically modulated LD biosynthesis and catabolism throughout neutrophil differentiation. Perturbing LD metabolism did not impair differentiation efficiency or lineage commitment, but significantly altered the functional output of mature neutrophils. In the murine system, inhibition of adipose triglyceride lipase (ATGL)-mediated LD breakdown enhanced reactive oxygen species (ROS) production and increased anti-tumor cytotoxicity against GL261 glioma cells. In the hPSC model, ATGL inhibition during the myeloid progenitor-to-neutrophil transition selectively increased intracellular LD accumulation without compromising neutrophil yield or purity. This metabolic rewiring also elevated ROS production in hPSC-derived neutrophils, although cytotoxic enhancement against U87MG glioblastoma cells was less pronounced than in the murine system. Collectively, these findings define a stage-specific LD metabolic landscape during neutrophil development and highlight targeted LD modulation as a potential strategy to enhance the functional potency of therapeutic neutrophils.
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6. Multimodal chromatography solutions for the removal of light chain impurity from a fab therapeutic.
6. 用于从晶圆厂治疗剂中去除轻链杂质的多模式色谱溶液PMID:日期:2026-08-17The production of Fab therapeutics is frequently challenged by an imbalanced expression of light chains (LC) and heavy chains (HC), often resulting in LC-associated impurities. In this work, we evaluated multimodal chromatography as an alternative to affinity chromatography for the removal of an LC impurity. A panel of multimodal CEX and multimodal AEX resins was screened using linear salt and pH gradients to assess Fab monomer and LC impurity selectivities. Product and impurity characterization was carried out using analytical size-exclusion chromatography. Screening data provided insight into the relative contributions of hydrophobic and electrostatic interactions in the Fab and LC impurity selectivities across different multimodal ligands. A previously developed separability scoring metric (Fractional Peak Overlap) was employed to identify Eshmuno HCX and CMM HyperCel as the top resin candidates from the screening data. Finally, bench-scale refinement was carried out to develop an Eshmuno HCX bind-elute step with a 95%-100% recovery and 95%-98% purity of Fab monomer and a CMM HyperCel bind-elute step with a 98%-99% recovery and 98% purity of Fab monomer. This work demonstrates the efficacy of this PD workflow and the utility of multimodal chromatography for removal of LC impurities from Fabs.
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7. Synergistic viral inactivation platform: Rapid enveloped virus inactivation at mildly acidic pH using low non-ionic detergent in Protein A eluates.
PMID:日期:2026-08-16Low-pH viral inactivation (LPVI) is a widely used, validated unit operation for enveloped virus clearance in antibody manufacturing. However, acid exposure during Protein A (ProA) elution and subsequent low-pH holds can destabilize some antibodies and Fc-containing modalities, increasing aggregation risk and product loss-a challenge that is particularly acute for multi-specific antibody formats and other pH-labile Fc-containing modalities. Mild-pH ProA capture strategies protect such molecules, but the resulting higher-pH eluates often require re-acidification to meet conventional LPVI setpoints, reintroducing low-pH stress. Here we evaluate a dual-mechanism strategy in which mild acidity is combined with low concentrations of non-ionic detergent to accelerate inactivation without prolonged exposure to strongly acidic conditions. Using xenotropic murine leukemia virus (X-MuLV) spiked into ProA eluates, 0.10% N-methylglucamide (Mega-10) at pH 3.91 reduced infectivity to below the assay limit of detection within 2.5 min (log10 reduction factor [LRF] ≥ 5.40), whereas low pH alone or detergent alone produced substantially lower reductions over the same interval. Similarly, 0.15% Mega-10 at pH 4.05 achieved nondetectable infectivity within 10 min (LRF ≥ 5.81). Comparable time compression was observed with Tween 80 or Tween 20 at pH ~3.97, reducing time-to-nondetectable infectivity from 120 min (low pH alone) to 5 min. The operating window was tunable through paired adjustment of detergent concentration and pH, and feasibility was demonstrated at pH 4.56 with low detergent levels, offering a practical solution for pH-labile products and higher-pH eluates.
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8. An empirical single-breakthrough curve workflow for rapid early-phase development of continuous capture chromatography for monoclonal antibodies and mAb-derived proteins.
PMID:日期:2026-08-06Continuous chromatography for Protein A capture of monoclonal antibodies (mAbs) and related biotherapeutics is gaining popularity for higher throughput and reduced costs but introduces challenges for development and modeling. We present a streamlined, single-breakthrough-curve approach that predicts maximum and operating binding capacities (MBC and OBC, respectively) for continuous Protein A chromatography of monoclonal antibodies and derivatives. Our empirically-calibrated model-intended for early-stage, material-limited process development-enables accurate OBC prediction (root mean squared error [RMSE]≤ 5% for four distinct proteins) using less than 1 g of protein. This approach reduces the experimental timeline by ~2 weeks and is best suited for rapid screening and initial process optimization, not full design-space determination. Results confirm the model's accuracy across molecules, with clear practical advantages for accelerating preclinical pipeline advancement.
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9. Infrared spectroscopy-based chemometric modeling for monitoring mesenchymal stem cell functional decline across donors.
PMID:日期:2026-08-02Reliable assessment of cellular state remains a challenge in cell therapy manufacturing and regenerative medicine. Proliferative capacity, senescence, and metabolic activity are traditionally measured using labor-intensive assays, limiting timely and integrated assessment of cellular state. Here, we apply attenuated total reflection-Fourier transform infrared spectroscopy coupled with multivariate analysis to assess whether intrinsic vibrational fingerprints of mesenchymal stem cells reflect coordinated functional changes during in vitro expansion. By integrating proliferation kinetics, metabolite fluxes, and senescence-associated phenotype into a composite functional score, we mapped progressive functional decline across passages onto infrared spectral changes. Spectral alterations were associated with shifts in lipid-related and protein-associated regions as senescence accumulated. Despite strong donor-specific differences, we identified conserved spectral fingerprint regions that tracked functional decline across donor samples analyzed. These shared biochemical signatures were associated with the prediction of senescence progression and the estimation of functional passage in an independent donor sample. Together, our results show that intrinsic vibrational fingerprints capture coordinated biochemical changes during cellular decline and provide a label-free, rapid means to assess cellular state.
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10. A biochemically structured predictive model of eukaryotic microalgal growth: Integrating radiative transfer, respiration, and pigment acclimation.
PMID:日期:2026-07-24Predictive modeling of phototrophic cultures in photobioreactors remains challenging because growth emerges from the coupling between radiative transfer, intracellular bioenergetics, and physiological acclimation. Although existing approaches have progressively integrated light attenuation and reactor-scale heterogeneity, extending knowledge-based formulations to eukaryotic microalgae still raises difficulties, especially regarding the role of respiration under illumination and the dynamic adjustment of pigment content. In this work, we establish a biochemically structured predictive model of photoautotrophic growth for the eukaryotic microalga Chlamydomonas reinhardtii. The model is built from an explicit stoichiometric decomposition of the main metabolic functions involved in biomass synthesis, pigment synthesis, photosynthetic energy conversion, respiration, and ATP-consuming futile processes under redox regulation. Its structure is derived from intracellular conservation relationships and observability analysis, leading to a reduced formulation driven by two variables: the net conversion rate of photochemically productive photons within the biotic phase, , and a dissipative ATP sink. The kinetic formulation explicitly couples growth to radiative transfer and accounts for dynamic pigment acclimation through variable partitioning of biomass formation between residual biomass and pigments. Model parameters were either fixed from previous physiological and bioenergetic analyses or identified from batch-culture experiments performed under different incident photon flux densities in a flat-panel photobioreactor illuminated from one side. The model satisfactorily predicts biomass and pigment dynamics in batch and continuous cultures over a broad range of light conditions and dilution rates, while comparisons with oxygen-exchange measurements under illumination provide additional support for its structural relevance. The proposed framework provides a predictive and mechanistically interpretable description of eukaryotic microalgal growth in photobioreactors.