CLR-124

近年来，肿瘤治疗领域正在经历快速演变，精准化、个性化以及靶向化治疗策略逐渐成为创新药物研发的重要方向。其中，抗体偶联药物（ADC）凭借其结合抗体靶向识别能力与高活性小分子药物杀伤作用的特点，成为肿瘤药物研发领域备受关注的重要技术路线。目前，全球已有多款ADC产品获批并有大量ADC候选药物进入临床开发阶段，覆盖乳腺癌、肺癌、胃癌、血液瘤等多个疾病领域。ADC技术的发展为提升肿瘤治疗效果提供了新的可能，但与此同时，其复杂的分子结构也对生产制造体系提出了更高要求。 与传统单抗或重组蛋白药物相比，ADC是一类典型的复杂偶联型生物药，其生产过程并非简单地将抗体和小分子药物进行组合，而是需要经历抗体表达与纯化、药物载荷制备、连接反应、偶联产物纯化以及质量控制等多个关键环节。由于ADC同时包含生物大分子和高活性化学药物组分，因此在生产过程中需要兼顾蛋白药物的稳定性和小分子毒性的控制，对工艺开发、设备系统、人员防护以及质量管理体系提出了更高要求。 ADC生产制造中的挑战往往隐藏在工艺细节之中。例如，抗体结构对外部环境较为敏感，温度变化、机械剪切、pH波动、氧化还原条件变化等因素，都可能影响抗体的空间结构、聚集状态以及最终药物活性。同时，偶联反应过程需要精确控制药物抗体比（即DAR）、连接位点分布以及反应均一性，以确保产品具有稳定的质量属性。如果这些关键参数控制不当，可能导致产品批次间差异增加，影响后续开发和商业化生产。 此外，ADC生产还涉及高活性药物成分（即HPAPI）的操作和管理，这对生产环境、密闭系统、污染控制以及人员安全提出了特殊要求。传统生物药生产平台虽然具备一定的生产基础，但并不意味着能够直接满足ADC制造的全部需求。企业在选择生产合作伙伴或建立自身生产能力时，需要重点评估其是否具备针对复杂偶联药物的工艺理解、设备配置和质量管理经验。 面对这些挑战，ADC生产制造需要从工艺开发、生产设备、质量控制以及供应链管理等多个方面进行系统优化，包括： 加强工艺开发与参数控制：通过深入理解偶联反应机制，建立稳定可靠的工艺窗口，降低批次差异，提高产品一致性； 优化生产系统与操作环境：根据ADC分子的特点，采用适合的反应、纯化和密闭操作方案，保障产品质量与人员安全； 完善分析检测与质量评价体系：针对DAR分布、聚集体、游离药物以及杂质等关键质量属性建立全面的检测方法； 提升放大生产和商业化支持能力：确保从实验室开发到临床样品制备，再到规模化生产过程中，工艺能够稳定转移和持续运行。 随着ADC技术不断发展，其生产制造模式也正在从早期研发探索逐步走向更加成熟的产业化阶段。对于药物开发企业而言，未来的核心问题不仅是如何开发具有创新性的ADC分子，更重要的是如何建立与其复杂性相匹配的制造能力。深入理解ADC生产过程中的关键挑战，并采取针对性的解决策略，将成为推动这类创新疗法安全、高效实现临床应用的重要基础。 一次性系统助力ADC生产降低制造风险 随着ADC等复杂生物药不断向临床开发和商业化阶段推进，生产制造过程对于安全性、灵活性以及风险控制能力提出了更高要求。在这一背景下，一次性系统（SUS）逐渐从早期作为传统不锈钢设备的补充方案，发展成为现代生物药生产体系中的重要组成部分。尤其是在涉及高活性、小剂量以及对环境条件高度敏感的药物生产过程中，一次性技术能够通过优化物料流转方式和生产环境管理，有效降低潜在生产风险。 与传统固定式设备相比，一次性系统采用预先设计和制造的一次性使用组件，如储液袋、管路、过滤组件、无菌连接器以及相关配套部件等，在完成特定生产任务后进行更换。这种模式减少了不同产品或不同批次之间共用设备带来的潜在影响，为多品种、小批量以及复杂药物生产提供了更高的灵活性。对于ADC这类同时包含生物大分子和高活性化学组分的药物而言，降低交叉污染风险、保障操作安全以及维持产品质量稳定尤为重要。 在ADC生产过程中，一次性系统的应用价值主要体现在以下几个方面： 降低交叉污染风险：通过采用独立的一次性流路，减少不同产品之间发生物料残留和交叉污染的可能性，特别适用于生产高活性药物或多种复杂分子的生产环境； 简化清洁验证流程：传统重复使用设备需要经过严格的清洁、消毒和残留验证，而一次性组件在使用后直接更换，可降低清洁验证相关的工作量，提高生产转换效率； 提升操作人员安全性：密闭式一次性系统能够减少人员与高活性物料直接接触的机会，在生产过程中提供更加受控的操作环境； 增强生产灵活性和工艺适配能力：一次性组件可以根据不同工艺需求进行设计和组合，例如调整管路布局、储液容量以及连接方式，以满足不同规模和不同阶段生产的需求。 除了降低物理污染和操作风险外，一次性系统在过程监控方面也发挥着越来越重要的作用。现代一次性生产组件通常可集成多种在线/入线监测技术，例如一次性温度、压力、pH、电导、溶氧等传感器，实现关键工艺参数的实时监测。对于ADC等结构复杂、稳定性要求较高的药物而言，生产过程中的微小变化都可能影响最终产品质量，因此及时获取过程数据并进行动态控制，有助于提高工艺稳定性和批次一致性。 需要注意的是，一次性系统并不是简单的设备替代，而是一种围绕质量风险管理和生产效率优化建立的制造策略。通过合理设计一次性生产流程，并结合完善的工艺控制和质量体系，可以帮助企业在满足GMP生产要求的同时，提高生产灵活性、缩短生产准备周期，并更好地应对创新药物快速发展带来的制造挑战。对于ADC等下一代复杂治疗产品而言，一次性技术正在成为支持其安全、稳定和规模化生产的重要基础设施。 过滤工艺控制对ADC产品稳定性的关键影响 在ADC的生产过程中，除菌过滤通常被认为是最终制剂阶段的重要质量控制环节，但由于其位于生产流程末端，且操作过程相对成熟，往往容易被低估其对产品质量的影响。实际上，对于ADC这类结构复杂、稳定性要求较高的创新型生物药而言，过滤并不仅仅是去除微生物和颗粒污染的简单步骤，而是一个需要综合考虑产品特性、工艺参数以及设备系统匹配性的关键控制过程。 ADC分子同时包含抗体部分和高活性药物载荷，其结构稳定性可能受到多种外部因素影响。在制剂过滤过程中，产品黏度、分子大小、浓度、过滤材料相容性以及操作条件等因素，都可能影响最终产品质量。尤其是部分ADC制剂具有较高浓度或较高黏度特征，使其在通过过滤膜时可能产生更大的流体阻力。如果过滤过程中的压力、流速或剪切条件控制不合理，可能导致抗体结构变化、蛋白聚集增加，甚至影响药物的活性和稳定性。 因此，在ADC生产中，过滤工艺需要在产品保护和生产效率之间取得平衡。一方面，需要确保过滤过程能够满足无菌保障要求，降低微生物污染风险；另一方面，也需要避免由于过度的工艺压力或不适宜的操作条件对敏感分子造成影响。通常情况下，过滤过程中的关键控制因素包括： 过滤压力控制：过高的跨膜压力可能增加蛋白分子受到的机械应力，导致聚集或结构变化，因此需要建立合理的压力控制范围； 流速优化：适当的流速能够在保证生产效率的同时减少对产品稳定性的影响，避免因过快过滤造成不必要的工艺风险； 过滤材料相容性评估：过滤膜材质需要与ADC制剂体系具有良好的兼容性，避免发生吸附、析出或其他相互作用； 过滤系统完整性验证：通过使用前和使用后的完整性检测，确认过滤组件在整个生产过程中的可靠性。 随着一次性技术在生物制药领域的应用不断深入，过滤系统也逐渐向更加集成化、密闭化方向发展。将过滤组件整合到一次性生产系统中，可以减少产品在转移过程中的外部暴露风险，同时降低人为操作带来的不确定性。此外，通过在线完成过滤器完整性测试，可以在过滤操作开始前确认系统状态，并在生产完成后验证过滤过程的有效性，从而进一步提升无菌保障水平。 因此，建立稳定、可验证且可放大的过滤工艺，不仅关系到产品无菌质量，也直接影响整体生产效率和批次一致性。通过对过滤参数、设备系统以及质量控制策略进行综合优化，可以更好地支持ADC从实验室开发向规模化生产阶段平稳过渡。 针对敏感ADC分子的无菌灌装工艺控制 在ADC生产流程中，经过过滤后的药液需要进入最终灌装阶段，而无菌灌装作为药物进入最终包装前的关键步骤，对产品质量和临床供应稳定性具有重要影响。由于ADC通常具有高活性、高价值以及较高的分子复杂性，其灌装过程不仅需要满足无菌保障要求，还需要充分考虑药物稳定性、操作精度以及批次一致性等多方面因素。因此，ADC的灌装工艺需要根据不同产品特性进行针对性设计，而不能简单套用传统制剂的生产模式。 在实际生产过程中，过滤后的ADC药液通常会在受控的无菌环境中转移至中间储存容器，并通过隔离器等封闭式系统完成后续灌装操作。这种设计能够减少药液与外部环境的接触机会，降低微生物污染风险，同时为操作人员提供更加安全的生产环境。对于涉及高活性药物载荷的ADC产品而言，密闭化和隔离化的生产方式也是保障人员安全和产品质量的重要措施。 由于ADC制剂通常以小体积、高浓度形式存在，每一支西林瓶中的灌装精度都会直接影响产品剂量准确性。因此，在灌装过程中，需要对关键参数进行精细化控制，例如： 灌装精度控制：通过在线称重或其他实时监测方式，对每个容器的灌装量进行确认，确保产品符合预设规格要求； 工艺参数优化：根据不同ADC分子的稳定性特点，调整灌装速度、设备运行条件以及物料处理方式，减少因机械应力或环境因素导致的产品变化； 无菌环境管理：通过隔离系统、无菌连接以及受控操作流程，降低整个灌装过程中的污染风险。 此外，不同ADC分子在稳定性、降解途径以及对外界条件的敏感程度方面存在差异，因此灌装工艺需要结合具体产品特征进行开发和验证。例如，部分分子可能对温度变化、光照、剪切力或停留时间更加敏感，在生产过程中需要针对这些因素进行优化，以维持药物结构完整性和功能活性。 对于处于临床开发阶段的ADC产品而言，灌装过程的稳定性尤为重要。即使是较小的批次差异，也可能影响临床样品的一致性以及后续质量评价。因此，通过建立可重复、可验证的无菌灌装流程，并结合严格的过程监控和质量管理体系，可以有效支持ADC产品从研发阶段向临床供应和规模化生产阶段平稳过渡。 多宁生物围绕ADC生产过程中的关键挑战，提供覆盖从物料储存、配液、偶联反应到无菌灌装的全流程一次性使用解决方案，助力实现安全、高效和稳定的生产。针对ADC工艺中高活性组分及有机溶剂使用特点，公司提供具备良好化学相容性的储液袋、工艺管组及一次性偶联反应器，并配套开展溶析出（E&L）相关评估，为产品质量控制提供数据支持。同时，基于不同工艺需求，可提供定制化超滤管组、层析管组、PUPSIT管组、一次性灌装管组等工艺管组以及结合高精度蠕动泵的灌装系统，帮助降低污染风险，提高灌装精度和过程一致性，支持ADC药物从研发、临床开发到规模化生产的工艺转化。 DuoMix® 一次性搅拌系统 多宁生物DuoMix®一次性搅拌系统专为生物制药工艺中的混合、配液及缓冲液制备等应用场景设计，具备优异的可放大性、灵活性和过程可控性。系统支持从实验室研发到商业化生产的规模化放大，确保不同阶段工艺参数的一致性与稳定性。DuoMix®可根据工艺需求配置pH、电导率、温度等多种传感器，实现关键参数的实时监测与精准控制，同时支持夹套控温，满足不同温度条件下的工艺需求。此外，多宁生物可提供专业的计算流体力学（CFD）分析，深入评估混合均一性、剪切力及传质效率，助力客户优化工艺设计与提升生产可靠性，为生物制药全过程提供高效、稳定的一次性混合解决方案。 一次性生物偶联反应器 针对ADC生产过程中对反应稳定性、温控精度及无菌安全性的高要求，多宁生物开发了一次性偶联反应器解决方案。该系统采用专为偶联工艺优化的磁悬浮搅拌技术，实现低摩擦、低热量输出的温和混合，满足长时间反应需求。同时，设备配备定制化搅拌电机绝热材料及五面蜂窝夹套设计，有效降低设备散热及反应放热对偶联效率的影响，提升温控稳定性。通过集成TCU与蠕动泵自动控制，实现精准控温和一体化操作，温度响应可控制在±0.5℃以内。此外，设备支持集成蠕动泵、限压保护及氮气保护设计，可满足小分子偶联过程中的惰性气体保护需求，为ADC药物开发及商业化生产提供安全、高效、灵活的一次性解决方案。 DuoMix® 一次性搅拌袋 多宁生物DuoMix® 一次性搅拌袋适用于多种生物工艺应用，包括ADC生产，提供从2 L到3000 L的全系列规格，并可根据客户需求定制具体配置，如搅拌桨结构、歧管连接形式等，灵活适配不同工艺单元操作。搅拌袋采用DuoFilm-001七层复合生物专用膜，厚度0.3 mm，液体接触层为ULDPE，具备优异的理化性能、生物相容性和溶剂耐受性，适用于多种配液和反应场景。针对ADC工艺中常用的溶剂，如DMSO、DMF和DMAC，多宁已完成可提取物分析研究，并可提供完整的验证报告，助力客户满足质量控制与法规合规要求。 一次性工艺管组 在ADC工艺中，一次性管组有助于降低交叉污染风险、提升操作效率并简化清洁验证流程，是实现高效、合规、可追溯生产的重要保障。多宁生物提供全面的一次性工艺管组产品，涵盖层析、超滤等关键单元操作，广泛适用于ADC等高附加值产品的生产需求。产品支持灵活设计，可定制管路布局、连接接口和组件配置，兼容市场上主流的层析与超滤系统，便于集成现有平台。管组可集成压力、电导、UV等关键在线监测组件，实现对工艺过程的精准控制。所有组件均通过严格的质量验证，确保在压力、流速和流体分布等关键参数上的稳定性与一致性。 一次性灌装组件解决方案 多宁生物提供面向高价值生物药生产的一次性灌装解决方案，覆盖从药液转移、无菌连接到终端灌装的全流程需求。针对ADC生产过程中高活性、高复杂性以及对无菌和材料相容性的严格要求，多宁生物提供经过验证的一次性灌装组件，采用高等级洁净环境预组装及伽马射线灭菌，集成入口连接器、储液袋、蠕动泵管路、灌装管路及灌装针头等关键部件，可灵活匹配不同灌装设备与容器形式。组件选用合规材料，具备优异的生物相容性、化学耐受性及低析出特性，并配套完整法规支持文件，助力ADC等高附加值药物实现安全、高效、可靠的无菌灌装。 DuoIsola™ 柔性隔离器 多宁DuoIsola™柔性隔离器是一款面向高活性、高毒性药物制造场景的新一代密闭防护解决方案，专为OEB≥4级物料操作设计。产品采用模块化柔性膜结构，结合负压控制、多级HEPA过滤及一次性组件设计，实现人员、产品与环境的高效隔离。其具备CPT <10 ng/m³的高水平密闭性能，支持快速部署、灵活配置及低维护运行，可广泛应用于ADC、HPAPI等创新药物研发及生产过程，为制药企业提供安全、高效、智能化的一站式隔离防护平台。 参考文献： Y.Matsuda, Current approaches for the purification of antibody-drug conjugates. J.Sep.Sci. 2022. L.Sorret, M.Ninomiya, N.Hillebrandt, et al., Antibody–Drug Conjugates Drug Product Formulation and Process Development, Scalability and Stability Considerations. AAPS PharmSciTech, 2026. Y.Matsuda, C.Clancy, Z.Tawfiq, et al., Good Manufacturing Practice Strategy for Antibody–Drug Conjugate Synthesis Using Site-Specific Chemical Conjugation: First-Generation AJICAP. ACS Omega, 2019. 关于多宁生物 上海多宁生物科技股份有限公司是一家中国领先的一站式生物工艺解决方案提供商，致力于提供生物制药产品从研发到商业化生产的综合解决方案，包括试剂及耗材、仪器设备、服务。公司主要运营生物工艺解决方案、实验室产品及服务两大业务线，通过一站式生物工艺体系帮助合作伙伴实现高效、稳定、质量及成本可控的药物研发及生产流程。 了解更多：www.duoningbio.com 媒体垂询：PR@duoningbio.com In recent years, the field of oncology treatment has undergone rapid transformation, with precision medicine, personalized therapies, and targeted treatment strategies becoming key directions in innovative drug development. Among these approaches, antibody-drug conjugates (ADCs) have emerged as a highly promising technology platform in oncology due to their unique combination of antibody-mediated target recognition and the potent cytotoxic effects of highly active small-molecule payloads. To date, multiple ADC products have been approved worldwide, and a large number of ADC candidates have entered clinical development, covering a broad range of therapeutic areas including breast cancer, lung cancer, gastric cancer, and hematological malignancies. While ADC technology provides new opportunities for improving cancer treatment outcomes, its complex molecular structure also introduces higher requirements for manufacturing systems and production capabilities. Compared with conventional monoclonal antibodies or recombinant protein therapeutics, ADCs are a typical class of complex conjugated biopharmaceutical products. Their manufacturing process is not simply a combination of antibodies and small-molecule drugs; rather, it involves multiple critical steps, including antibody production and purification, payload preparation, conjugation reactions, purification of conjugated products, and comprehensive quality control. Since ADCs contain both biological macromolecules and highly potent chemical drug components, the manufacturing process must simultaneously ensure protein stability and control the risks associated with cytotoxic small molecules. This creates higher demands on process development, equipment systems, personnel protection, and quality management frameworks. The challenges associated with ADC manufacturing are often embedded in detailed process parameters. For example, antibody structures are highly sensitive to environmental conditions. Factors such as temperature fluctuations, mechanical shear, pH variations, and changes in redox conditions may affect antibody conformation, aggregation behavior, and final product activity. Meanwhile, the conjugation process requires precise control of critical parameters, including the drug-to-antibody ratio (DAR), distribution of conjugation sites, and reaction uniformity, to ensure consistent product quality attributes. Inadequate control of these parameters may increase batch-to-batch variability and negatively impact subsequent development and commercial manufacturing. Furthermore, ADC manufacturing involves the handling and management of highly potent active pharmaceutical ingredients (HPAPIs), which introduces additional requirements for production environments, closed processing systems, contamination control, and personnel safety. Although traditional biopharmaceutical manufacturing platforms provide a certain foundation, they may not fully meet all the specific requirements of ADC production. When selecting manufacturing partners or establishing internal manufacturing capabilities, companies need to carefully evaluate whether they possess sufficient expertise in complex conjugation processes, appropriate equipment configurations, and quality management experience. To address these challenges, ADC manufacturing requires systematic optimization across multiple areas, including process development, production systems, quality control, and supply chain management. Key strategies include: Strengthening process development and parameter control: By gaining a deeper understanding  of conjugation reaction mechanisms, companies can establish robust process windows, reduce batch variability, and improve product consistency. Optimizing manufacturing systems and operating environments: Based on the characteristics of ADC molecules, appropriate reaction, purification, and closed processing solutions should be implemented to ensure product quality and personnel safety. Enhancing analytical testing and quality evaluation systems: Comprehensive analytical methods should be established for critical quality attributes, including DAR distribution, aggregates, free drug content, and process-related impurities. Improving scale-up manufacturing and commercial production capabilities:      Manufacturing processes should be designed to enable reliable technology transfer and consistent operation from laboratory development to clinical material production and large-scale commercial manufacturing. As ADC technology continues to evolve, manufacturing approaches are gradually transitioning from early-stage research exploration toward more mature industrial production models. For drug developers, the key challenge in the future will not only be the discovery of innovative ADC molecules but also the establishment of manufacturing capabilities that match their inherent complexity. A comprehensive understanding of the critical challenges in ADC manufacturing, combined with targeted solutions, will serve as an essential foundation for enabling the safe, efficient, and successful clinical application of these innovative therapies. Reducing Manufacturing Risks in ADC Production Through Single-Use Systems As complex biopharmaceutical products such as ADCs continue to advance toward clinical development and commercial manufacturing, production processes face increasingly stringent requirements for safety, flexibility, and risk management. In this context, single-use systems (SUS) have gradually evolved from an early-stage supplementary solution to traditional stainless-steel equipment into an essential component of modern biopharmaceutical manufacturing platforms. Particularly in the production of highly potent, low-dose, and environmentally sensitive drug products, single-use technologies can effectively reduce potential manufacturing risks by optimizing material handling processes and improving production environment control. Compared with traditional fixed equipment systems, single-use systems utilize pre-designed and pre-manufactured disposable components, including storage bags, tubing assemblies, filtration components, sterile connectors, and other related accessories. These components are replaced after completion of a specific manufacturing operation. This approach minimizes potential impacts associated with shared equipment usage between different products or batches, providing greater flexibility for multi-product, small-batch, and complex drug manufacturing. For ADCs, which contain both biological macromolecules and highly potent chemical components, reducing cross-contamination risks, ensuring operator safety, and maintaining consistent product quality are particularly critical. In ADC manufacturing, the value of single-use systems is primarily reflected in the following areas: Reducing cross-contamination risks: By utilizing dedicated disposable fluid pathways, single-use systems minimize the potential for material carryover and cross-contamination between different products. This is particularly suitable for manufacturing environments involving highly potent drugs or multiple complex molecules. Simplifying cleaning validation processes: Traditional reusable equipment requires rigorous cleaning, sanitization, and residue validation procedures. Single-use components can be directly replaced after use, reducing the workload associated with cleaning validation and improving manufacturing changeover efficiency. Enhancing operator safety: Closed single-use systems reduce opportunities for direct operator exposure to highly potent materials, providing a more controlled and safer operating environment during manufacturing. Improving manufacturing flexibility and process adaptability: Single-use components can be customized and configured according to different process requirements, including adjustments to tubing layouts,  storage capacities, and connection methods, enabling support for different production scales and development stages. Beyond reducing physical contamination and operational risks, single-use systems are also playing an increasingly important role in process monitoring. Modern single-use assemblies can integrate various online or in-line monitoring technologies, such as disposable sensors for temperature, pressure, pH, conductivity, and dissolved oxygen, enabling real-time monitoring of critical process parameters. For complex molecules such as ADCs, where product stability requirements are highly stringent, even minor variations during manufacturing may affect final product quality. Therefore, timely acquisition of process data and dynamic process control can help improve process robustness and batch-to-batch consistency. It is important to recognize that single-use systems are not simply replacements for traditional equipment, but rather a manufacturing strategy built around quality risk management and operational efficiency optimization. Through the rational design of single-use manufacturing workflows, combined with comprehensive process control and quality management systems, companies can meet GMP manufacturing requirements while improving production flexibility, shortening preparation and changeover times, and better addressing the manufacturing challenges associated with rapidly evolving innovative therapies. For next-generation complex therapeutic products such as ADCs, single-use technology is becoming an essential foundation for safe, reliable, and scalable manufacturing. The Critical Impact of Filtration Process Control on ADC Product Stability During ADC manufacturing, sterile filtration is generally regarded as an important quality control step in the final formulation stage. However, because it is positioned at the end of the manufacturing process and involves relatively mature operating procedures, its potential impact on product quality is often underestimated. In reality, for complex and highly sensitive innovative biopharmaceuticals such as ADCs, filtration is not merely a simple step for removing microorganisms and particulate contaminants. Instead, it is a critical process control operation that requires comprehensive consideration of product characteristics, process parameters, and compatibility between the equipment system and the product. ADC molecules consist of both antibody components and highly potent drug payloads, and their structural stability can be influenced by various external factors. During formulation filtration, parameters such as product viscosity, molecular size, concentration, filter material compatibility, and operating conditions may all affect final product quality. In particular, some ADC formulations have relatively high concentrations or viscosities, which may result in increased fluid resistance during membrane filtration. If filtration pressure, flow rate, or shear conditions are not properly controlled, potential risks may include changes in antibody structure, increased protein aggregation, and impacts on drug activity and stability. Therefore, filtration processes in ADC manufacturing need to achieve an appropriate balance between product protection and manufacturing efficiency. On one hand, the filtration process must ensure sterility assurance and reduce the risk of microbial contamination. On the other hand, it must avoid exposing sensitive molecules to excessive process pressure or unsuitable operating conditions. In general, key control factors during filtration include: Filtration pressure control: Excessive transmembrane pressure may increase mechanical stress on protein molecules, potentially causing aggregation or structural changes. Therefore, an appropriate pressure control range needs to be established. Flow rate optimization: An appropriate flow rate can maintain manufacturing efficiency while minimizing potential impacts on product stability and avoiding unnecessary process risks caused by excessive filtration rates. Evaluation of filter material compatibility: Filter membrane materials must demonstrate good compatibility with ADC formulations to avoid adsorption, extractables/leachables, or other unwanted interactions. Filtration system integrity verification: Pre-use and post-use integrity testing should be performed to confirm the reliability and performance of filtration components throughout the manufacturing process. With the increasing adoption of single-use technologies in biopharmaceutical manufacturing, filtration systems are also evolving toward more integrated and closed configurations. Integrating filtration components into single-use manufacturing systems can reduce the risk of product exposure during transfer operations while minimizing variability caused by manual handling. In addition, performing in-line filter integrity testing enables confirmation of system status before filtration begins and verification of filtration effectiveness after completion, further enhancing sterility assurance. Therefore, establishing a robust, scalable, and fully validated filtration process is critical not only for ensuring product sterility but also for improving overall manufacturing efficiency and batch-to-batch consistency. Through comprehensive optimization of filtration parameters, equipment systems, and quality control strategies, ADC manufacturing can achieve a smoother transition from laboratory development to large-scale production. Aseptic Filling Process Control for Sensitive ADC Molecules During the ADC manufacturing process, the filtered drug product solution proceeds to the final filling stage. As a critical step before the drug product enters final packaging, aseptic filling has a significant impact on product quality and the stability of clinical supply. Since ADCs typically feature high potency, high value, and complex molecular structures, their filling processes must not only meet stringent sterility assurance requirements but also address multiple considerations, including product stability, operational precision, and batch-to-batch consistency. Therefore, ADC filling processes need to be specifically designed based on the characteristics of each product rather than simply applying conventional formulation filling approaches. In actual manufacturing operations, the filtered ADC drug solution is typically transferred under controlled aseptic conditions into intermediate storage containers and then subjected to subsequent filling operations through closed systems such as isolators. This design reduces opportunities for product exposure to the external environment, minimizes the risk of microbial contamination, and provides a safer manufacturing environment for operators. For ADC products containing highly potent drug payloads, closed and isolated manufacturing approaches are also critical measures for ensuring both operator safety and product quality. Since ADC formulations are typically produced in small-volume, high-concentration formats, filling accuracy for each vial directly affects dose accuracy and product specifications. Therefore, precise control of critical parameters is required during the filling process, including: Filling accuracy control: Real-time monitoring methods, such as in-line weighing systems, are used to verify the fill volume of each container and ensure that the product meets predefined specifications. Process parameter optimization: Based on the stability characteristics of different ADC molecules, filling speed, equipment operating conditions, and material handling procedures should be optimized to minimize product changes caused by mechanical stress or environmental factors. Aseptic environment management: The use of isolation systems, sterile connections, and controlled operating procedures helps reduce contamination risks throughout the filling process. In addition, different ADC molecules may vary in terms of stability, degradation pathways, and sensitivity to external conditions. Therefore, filling processes need to be developed and validated based on specific product characteristics. For example, some molecules may be more sensitive to temperature fluctuations, light exposure, shear forces, or processing hold times. Appropriate process optimization strategies should be implemented to maintain molecular integrity and functional activity throughout manufacturing. For ADC products in clinical development, the robustness of the filling process is particularly important. Even minor batch-to-batch variations may affect the consistency of clinical materials and subsequent quality evaluations. Therefore, establishing a reproducible and validated aseptic filling process, combined with stringent process monitoring and quality management systems, can effectively support the smooth transition of ADC products from development stages to clinical supply and large-scale commercial manufacturing. Addressing the key challenges associated with ADC manufacturing, Duoning Biotech provides comprehensive single-use solutions covering the entire production workflow, from material storage, buffer preparation, and conjugation reactions to aseptic filling. These solutions are designed to support safe, efficient, and reliable ADC manufacturing processes. Considering the characteristics of highly potent components and the use of organic solvents in ADC processes, Duoning provides storage bags, process tubing assemblies, and single-use conjugation reactors with excellent chemical compatibility. In addition, extractables and leachables (E&L) evaluations are conducted to provide data support for product quality control. Based on specific process requirements, Duoning also provides customized process assemblies, including ultrafiltration tubing assemblies, chromatography tubing assemblies, PUPSIT assemblies, and single-use filling assemblies, as well as filling systems integrated with high-precision peristaltic pumps. These solutions help reduce contamination risks, improve filling accuracy and process consistency, and support seamless process transfer of ADC products from research and development to clinical manufacturing and commercial-scale production. DuoMix® Single-Use Mixing System Duoning Biotech’s DuoMix® Single-Use Mixing System is specifically designed for mixing, solution preparation, and buffer preparation applications in biopharmaceutical processes, offering excellent scalability, flexibility, and process controllability. The system supports seamless scale-up from laboratory development to commercial manufacturing, ensuring consistency and stability of process parameters throughout different production stages. DuoMix® can be configured with various sensors, including pH, conductivity, and temperature sensors, according to specific process requirements, enabling real-time monitoring and precise control of critical process parameters. The system also supports jacketed temperature control to meet process requirements under different temperature conditions. In addition, Duoning Biotech provides professional computational fluid dynamics (CFD) analysis to comprehensively evaluate mixing uniformity, shear stress, and mass transfer efficiency. These capabilities help customers optimize process design, enhance manufacturing reliability, and achieve efficient and stable single-use mixing solutions throughout the biopharmaceutical production lifecycle. Single-use Bioconjugation Reactor To address the stringent requirements for reaction stability, temperature control accuracy, and aseptic safety during ADC manufacturing, Duoning Biotech has developed a single-use bioconjugation reactor solution. The system adopts a magnetic levitation mixing technology specifically optimized for conjugation processes, enabling gentle mixing with low friction and minimal heat generation to meet the requirements of long-duration reactions. Meanwhile, the reactor is equipped with customized thermal insulation materials for the mixing motor and a five-sided honeycomb jacket design, effectively reducing heat dissipation from the equipment and minimizing the impact of reaction heat release on conjugation efficiency, thereby improving temperature control stability. By integrating TCU and peristaltic pump automatic control, the system enables precise temperature regulation and integrated operation, with temperature response accuracy controlled within ±0.5°C. In addition, the reactor supports integrated peristaltic pumps, pressure-limit protection, and nitrogen protection designs to meet the inert gas protection requirements of small-molecule conjugation processes. It provides a safe, efficient, and flexible single-use solution for ADC drug development and commercial-scale manufacturing. Single-Use Filling Assembly Duoning Biotech provides single-use filling solutions designed for high-value biopharmaceutical manufacturing, covering the complete workflow from drug product transfer and sterile connection to final aseptic filling. Considering the high potency, complex molecular characteristics, and stringent requirements for sterility and material compatibility in ADC manufacturing, Duoning provides validated single-use filling assemblies manufactured through pre-assembly in high-grade cleanroom environments and gamma sterilization. The assemblies integrate key components, including inlet connectors, storage bags, peristaltic pump tubing, filling tubing, and filling needles, and can be flexibly configured for different filling equipment and container formats. The components are manufactured using compliant materials with excellent biocompatibility, chemical resistance, and low extractables characteristics. Supported by comprehensive regulatory documentation, these solutions enable safe, efficient, and reliable aseptic filling of ADCs and other high-value pharmaceutical products. DuoIsola™ Flexible Isolator Duoning DuoIsola™ Flexible Isolator is a next-generation containment protection solution designed for high-potency and highly toxic drug manufacturing applications. Specifically developed for OEB ≥4 material handling, it features a modular flexible film structure combined with negative pressure control, multi-stage HEPA filtration, and single-use components to achieve effective isolation between operators, products, and the environment. With a high-level containment performance of CPT <10 ng/m³, DuoIsola™ enables rapid deployment, flexible configuration, and low-maintenance operation. It is widely applicable in the R&D and manufacturing processes of innovative therapies such as ADCs and HPAPIs, providing pharmaceutical companies with a safe, efficient, and intelligent one-stop containment platform. References: Y.Matsuda, Current approaches for the purification of antibody-drug conjugates. J.Sep.Sci. 2022. L.Sorret, M.Ninomiya, N.Hillebrandt, et al., Antibody–Drug Conjugates Drug Product Formulation and Process Development, Scalability and Stability Considerations. AAPS PharmSciTech, 2026. Y.Matsuda, C.Clancy, Z.Tawfiq, et al., Good Manufacturing Practice Strategy for Antibody–Drug Conjugate Synthesis Using Site-Specific Chemical Conjugation: First-Generation AJICAP. ACS Omega, 2019. Shanghai Duoning Biotechnology Co., Ltd. Is a leading one-stop bioprocess solutions provider, dedicated to offering comprehensive solutions for biopharmaceutical products from R&D to commercial manufacturing, including reagents and consumables, instruments and equipment, and services. The company primarily operates two business segments: bioprocess solutions and laboratory products & services. Through its one-stop bioprocess platform, we help partners achieve efficient, stable, and cost- and quality-controlled drug development and manufacturing processes. Learn more: www.duoningbio.com Media: PR@duoningbio.com Swipe left/right to switch languages (CN/EN)

再生医学的难题，正从“有没有细胞或材料”转向“能否把细胞、结构、力学与质量控制组织成可重复的系统”。近期的几项研究覆盖皮肤、软骨、骨与肠道，也延伸到干细胞识别和标准化参照资源。 01 · 全层创面｜自体表皮干细胞｜随机试验术中加入自体表皮干细胞，能否同时改善愈合与瘢痕？ 在全层皮肤缺损患者中，术中制备的自体表皮干细胞联合复合移植改善了早期闭合和6个月瘢痕表现。 该研究开展随机对照试验，纳入232例面积不小于9cm²的全层皮肤缺损患者。标准治疗组112例接受脱细胞真皮基质联合刃厚皮移植，细胞治疗组120例在此基础上加入术中一步制备的自体表皮干细胞悬液。 细胞治疗组6个月温哥华瘢痕量表总分中位数为3.0，标准组为6.0；2周完全愈合率分别为66.7%和54.5%，校正OR为1.87。分析还发现，2周完全愈合与较低的3个月复发风险相关，但这一关联本身不能证明早期闭合直接阻止复发。 关键数据 总样本量232例：细胞治疗组120例，标准治疗组112例6个 月VSS总分中位数：3.0比6.0，p＜0.001 2周完全愈合率：66.7%比54.5%，校正OR 1.87 2周完全愈合与3个月复发较少相关：校正OR 0.26 这项研究值得关注的地方 提供了患者层面的随机证据，也展示了无需长期体外扩增的术中细胞制备路径。 注： 观察期覆盖2周愈合、3个月复发和6个月瘢痕，长期耐久性仍需验证；部分作者持有相关技术专利。 02 · 软骨修复｜孔径力学｜山羊模型软骨支架并非孔越大越好，1.2毫米结构给出不同答案 研究把孔径与力学环境放在一起比较，发现较小孔径支架更支持山羊骨髓间充质干细胞软骨分化。 该研究构建胶原—透明质酸—聚乙烯醇水凝胶，系统比较1.2、1.4和1.6mm三种孔径及其伴随的力学差异。研究先观察山羊骨髓间充质干细胞14天内的黏附、增殖和分化，再用于山羊全层骨软骨缺损模型。 1.2mm支架具有三组中最低且更稳定的压缩模量，并促进细胞黏附、铺展和持续增殖；SOX9、Ⅱ型胶原和聚集蛋白聚糖表达高于较大孔径组。该组还伴随整合素β1—FAK—RhoA/ROCK轴活化。山羊模型中可见宿主组织整合、软骨下骨再生及富含蛋白聚糖的透明软骨样组织。 关键数据 比较孔径：1.2、1.4和1.6 mm 体外持续观察时间：14天 1.2 mm组SOX9、COL-II和聚集蛋白聚糖表达增加 山羊模型形成富含蛋白聚糖的透明软骨样组织 这项研究值得关注的地方 提示支架孔结构与力学性质需要协同设计，而不能只追求更高孔隙或更大孔径。 注： 机制证据主要来自山羊细胞实验，修复效果来自山羊模型，不能直接等同于人体关节软骨疗效。 03 · 骨支架｜数字光处理｜原位矿化打印后再原位矿化，陶瓷骨支架能否摆脱脆性取舍？ 反应性陶瓷—聚合物支架在低温水解后形成纳米晶网络，同时提高强度、韧性并保留一定柔性。 该研究将反应性α-磷酸三钙颗粒加入PEGDA光交联树脂，采用液晶显示数字光处理打印回旋曲面骨支架。成品含50wt%α-磷酸三钙，设计开放孔隙率为50%，随后通过打印后原位水解形成矿物相。 超过92%的α-磷酸三钙转化为仿生缺钙羟基磷灰石，并形成相互缠结的高长径比纳米晶网络。与刚打印完成时相比，支架抗压强度接近翻倍；相较传统烧结磷酸钙支架，应变能密度也接近提高两倍，同时显示良好体外细胞相容性。这说明打印后的化学转化可参与力学强化。 关键数据 α-磷酸三钙含量：50 wt% 设计开放孔隙率：50% 原位转化率：超过92% 抗压强度及应变能密度均接近提高两倍 这项研究值得关注的地方 把高分辨率成形与低温原位硬化结合，为兼顾复杂结构、强度和柔性提供材料路线。 注： 证据集中于材料性能和体外细胞相容性，尚不能判断植入后的骨整合、降解与长期承载表现。 04 · 肠道修复｜基质血管组分｜MXene自体混合细胞加二维材料，能否构建更完整的肠道修复单元？ 三维打印复合构建物同时支持伤口闭合、血管样结构形成和上皮增殖，为肠道修复提供体外线索。 该研究将脂肪来源的基质血管组分包埋于GelMA水凝胶，并加入MXene进行功能化和三维生物打印。研究先在多种细胞类型中评估MXene相容性，再检测复合构建物对创面闭合、内皮成管、上皮增殖及活性氧水平的影响。 含MXene的基质血管组分构建物促进了体外伤口闭合、内皮管样结构形成和上皮细胞增殖，同时维持稳定且无毒的活性氧水平，并表现出良好细胞相容性。结果提示，异质性自体细胞群与功能材料可以在同一构建物中共同支持上皮和血管相关过程，但尚不能据此确认肠道组织内的修复效果。 关键数据 构建组成：基质血管组分、GelMA与MXene 采用三维生物打印形成复合构建物 观察到伤口闭合、内皮成管和上皮增殖增强 活性氧维持在稳定且无毒水平 这项研究值得关注的地方 把上皮修复、基质支持和血管重塑纳入同一体外平台，拓展了复杂肠道损伤的材料设计思路。 注： 结果来自体外构建物与细胞功能实验，不能外推至炎症性肠病、胃肠瘘患者或体内安全性。 05 · 多孔水凝胶｜传质调控｜共非溶剂效应只改溶剂配比，能否同时调节水凝胶的孔、扩散与硬度？ 利用聚合物共非溶剂效应，研究者在水凝胶和微凝胶中联动调节孔径、分子扩散和材料刚度。 该研究利用二甲基丙烯酰胺和羟乙基丙烯酰胺聚合物在水—乙腈混合体系中的共非溶剂效应，通过改变合成时乙腈含量制备多孔水凝胶与微凝胶，并用显微成像、流变、纳米压痕及荧光漂白恢复分析结构和性能。 所得网络孔径可调至数微米，刚度覆盖数kPa至超过100kPa；4kDaFITC-葡聚糖的扩散系数可从50调至超过130μm²/s。水凝胶与微凝胶呈现相近的孔径和连通性变化，说明溶剂配比可作为同时调节传质与力学性质的制造参数，而其生物学功能仍有待具体体系验证。 关键数据 孔径可调至数微米 刚度范围：数kPa至超过100 kPa 4 kDa FITC-葡聚糖扩散系数：50至超过130 μm²/s 水凝胶与微凝胶具有相近的孔径及连通性趋势 这项研究值得关注的地方 提供了无需复杂模板即可联动控制孔隙、扩散和硬度的方法，适合后续构建可量化微环境。 注： 研究聚焦材料结构和物理性能，尚未证明其能改善细胞行为、组织修复或药物递送效果。 06 · 鼻骨骨折｜复合水凝胶｜大鼠模型药物纳米粒、脂肪干细胞与胶原凝胶组合后修复更好吗？ 在大鼠鼻骨骨折模型中，三组分复合水凝胶呈现更完整的组织修复，并伴随炎症和成骨指标变化。 该研究制备负载人参皂苷Rg1的壳聚糖纳米粒，并将其与胶原水凝胶及脂肪来源干细胞组合。体外评估颗粒释放、凝胶结构、细胞活性、降解和抗氧化能力，随后在大鼠鼻骨骨折模型中进行组织学、组织形态计量及生物标志物检测。 纳米粒先出现突释，随后持续释放至72小时；凝胶内脂肪来源干细胞的活性和代谢维持至7天，各凝胶组在12天内持续降解。动物实验中，同时含细胞和载药纳米粒的水凝胶总体修复反应最佳，表现为组织排列、胶原沉积和新骨形成改善，并伴随促炎细胞因子降低及抗炎、血管生成和成骨相关指标升高。 关键数据 药物释放由初始突释转为持续释放至72小时 凝胶内细胞活性和代谢维持至7天 各水凝胶组持续降解12天 三组分水凝胶在大鼠模型中总体修复反应最佳 这项研究值得关注的地方 展示了支架、细胞和局部递药协同构建修复微环境的组合策略。 注： 证据来自体外实验和大鼠鼻骨骨折模型；各组分的独立贡献及人体疗效仍需进一步检验。 07 · 细胞质控｜电化学生物传感｜CD105不靠单次流式检测，培养中的间充质干细胞能被快速识别吗？ 金—石墨烯纳米纤维传感器可按CD105表达识别犬间充质干细胞，为培养过程质控提供候选工具。 该研究以含氨基化石墨烯和金纳米粒的PCL—明胶电纺纳米纤维构建导电界面，并共价固定CD105抗体，用于检测CD105阳性的犬间充质干细胞。传感结果同时以荧光激活细胞分选进行验证，并考察选择性和低温储存稳定性。 传感器在78至10000个细胞范围内呈线性、成比例的电化学响应，实际检出限为312个细胞，交叉反应可忽略。4℃储存两周后，响应仍高于初始值的70%。这些结果支持其作为犬间充质干细胞表型检测工具，但CD105阳性只能反映特定表面标志，不能单独证明细胞的多能性或治疗效力。 关键数据 线性检测范围：78至10000个细胞 实际检出限：312个细胞 交叉反应可忽略 4 ℃储存两周后响应高于初始值的70% 这项研究值得关注的地方 把细胞表面标志检测转化为可量化电化学信号，为细胞制品过程监测提供另一种技术路径。 注： 验证对象为犬间充质干细胞，且检测目标仅为CD105；在人源细胞和复杂生产环境中的性能仍需验证。 08 · 人源iPSC｜参照细胞系｜克隆差异疾病模型的对照不应只有一株：多克隆参照面板如何建立？ 来自同一供者的多个iPSC克隆被纳入标准化参照面板，可帮助研究者识别供者差异与克隆差异。 该研究从5名健康供者的外周血单个核细胞建立人诱导多能干细胞资源，其中女性3名、男性2名。研究采用非整合型仙台病毒重编程，共生成并深入表征13个iPSC克隆，并有意为同一供者建立多个克隆。 最终形成由13个经过验证的iPSC克隆组成的参照面板，并向学术和商业研究者开放。多克隆设计使研究者能够在相同供者背景下观察和控制克隆间变异，减少把单一克隆特征误认为供者或疾病效应的风险。该成果的核心是标准化研究资源，而非证明某种细胞治疗或疾病模型已经有效。 关键数据 健康供者共5名 供者构成：女性3名、男性2名 共生成并表征13个iPSC克隆 采用非整合型仙台病毒完成重编程 这项研究值得关注的地方 为疾病建模和组织工程提供可共享对照，也把克隆差异纳入实验设计而非事后解释。 注： 这是细胞资源建立工作；面板规模有限，其在不同分化体系和实验室中的功能一致性仍需使用者继续验证。 值得关注的趋势 01｜微环境设计从单参数走向协同调控 孔径、力学、传质、矿化和递药不再被分开处理。多项研究尝试用同一支架同时调节细胞进入、分化信号、物质交换与组织承载，但参数之间的独立贡献仍需拆分验证。 02｜转化链条开始覆盖制造与质量控制 术中一步制备、低温原位硬化、电化学细胞识别及标准化iPSC参照面板共同指向一个变化：再生医学不仅要证明生物学活性，还要回答如何稳定生产、比较和放行。 03｜证据层级仍高度不均衡 患者随机试验提供了较强临床证据，其余多数结果来自材料测试、体外细胞或山羊、大鼠模型。机制线索和动物修复表型可以指导下一步实验，却不能替代人体安全性、长期耐久性与真实临床获益。 参考文献 1. Hu Z, Yang H, Wang P, Cao X, Wang P, Tang B, Xu H, Wang Z, Huang S, Zhang J, Xue C, Zhou Q, Li X, Wu H, Zhang Y, Xie J, Zhu J. Bio-Inspired Skin Reconstruction Using Intraoperative Autologous Epidermal Stem Cell-Enhanced Composite Grafts: A Randomized Trial. MedComm (2020). 2026 Sep 6;7(9):e70973. PubMed：https://pubmed.ncbi.nlm.nih.gov/42707312/ DOI：https://doi.org/10.1002/mco2.70973 2. Chen P, Lu W, Wang H, Liu T, Jiang Q, Yang L, Hu Y. Synergistic Tuning of Pore Architecture and Mechanical Properties in a Biomimetic COL-HA-PVA Hydrogel Directs BMSC Chondrogenesis for Osteochondral Regeneration. ACS Biomater Sci Eng. 2026 Sep 8. PubMed：https://pubmed.ncbi.nlm.nih.gov/42710039/ DOI：https://doi.org/10.1021/acsbiomaterials.6c00857 3. Fagotto-Clavijo R, Lodoso-Torrecilla I, Diez-Escudero A, Ginebra MP. Digital Light Processing of Reactive Ceramic-Polymer Bone Scaffolds Enables In situ Hydroxyapatite Formation. Acta Biomater. 2026 Sep 5:S1742-7061(26)00602-1. PubMed：https://pubmed.ncbi.nlm.nih.gov/42700782/ DOI：https://doi.org/10.1016/j.actbio.2026.09.013 4. Perini G, Minopoli A, Giulio GD, Montescagli M, Augello A, Ferrara V, Evangelista D, Marras M, Artemi G, Caretto AA, Gentileschi S, Nachira D, Zambrano D, Munir S, Pontecorvi V, Spada C, Gualtieri L, Rosenkranz A, Palmieri V, Boskoski I, Spirito M, Papi M. 3D bioprinting of stromal vascular fraction enriched with MXenes for enhanced intestinal regeneration. Biofabrication. 2026 Sep 9;18(3). PubMed：https://pubmed.ncbi.nlm.nih.gov/42612693/ DOI：https://doi.org/10.1088/1758-5090/ae9b71 5. Pieper MI, Stöbener DD, Häßel B, Hoogenboom R, Pich A. Cononsolvency-Assisted Fabrication of Hydrogels and Microgels With Tunable Porosity, Diffusivity and Stiffness. Macromol Rapid Commun. 2026 Sep 5:e70423. PubMed：https://pubmed.ncbi.nlm.nih.gov/42701100/ DOI：https://doi.org/10.1002/marc.70423 6. Wang X, Diao R. Collagen hydrogel incorporated with ginsenoside Rg1-loaded chitosan nanoparticles and adipose-derived stem cells enhances nasal bone fracture healing in rats. Int J Artif Organs. 2026 Sep 6:3913988261461129. PubMed：https://pubmed.ncbi.nlm.nih.gov/42703008/ DOI：https://doi.org/10.1177/03913988261461129 7. Prakashan D, Amarnath CA, Sawant SN, Sharma GT, Gandhi S. Gold-graphene based nanofiber biosensor for selective electrochemical identification of CD105-positive canine mesenchymal stem cells. Mikrochim Acta. 2026 Sep 5;193(10):661. PubMed：https://pubmed.ncbi.nlm.nih.gov/42700209/ DOI：https://doi.org/10.1007/s00604-026-08394-9 8. Stein E, Mosca E, John J, Kinzer M, Novatchkova M, Scheuch H, Agu C, Stary G, Penninger JM, Meixner A, Volz-Glaser J. Generation of high-quality reference control panels of human induced pluripotent stem cell clones from PBMCs. Stem Cell Res. 2026 Sep 6;96:104097. PubMed：https://pubmed.ncbi.nlm.nih.gov/42704963/ DOI：https://doi.org/10.1016/j.scr.2026.104097 责编|探索君 排版|探索君 转载请注明来源于【生物探索】 声明：本文仅用于分享，不代表平台立场，如涉及版权等问题，请尽快联系我们，我们第一时间更正，谢谢！ End