Oliveira Micaela, Conceição Pedro, Kant Krishna, Ainla Alar, Diéguez Lorena
Medical Devices Research Group, International Iberian Nanotechnology Laboratory (INL), 4715-330 Braga, Portugal.
Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal.
Cancers (Basel). 2021 Mar 18;13(6):1381. doi: 10.3390/cancers13061381.
Currently, conventional pre-clinical in vitro studies are primarily based on two-dimensional (2D) cell culture models, which are usually limited in mimicking the real three-dimensional (3D) physiological conditions, cell heterogeneity, cell to cell interaction, and extracellular matrix (ECM) present in living tissues. Traditionally, animal models are used to mimic the 3D environment of tissues and organs, but they suffer from high costs, are time consuming, bring up ethical concerns, and still present many differences when compared to the human body. The applications of microfluidic-based 3D cell culture models are advantageous and useful as they include 3D multicellular model systems (MCMS). These models have demonstrated potential to simulate the in vivo 3D microenvironment with relatively low cost and high throughput. The incorporation of monitoring capabilities in the MCMS has also been explored to evaluate in real time biophysical and chemical parameters of the system, for example temperature, oxygen, pH, and metabolites. Electrochemical sensing is considered as one of the most sensitive and commercially adapted technologies for bio-sensing applications. Amalgamation of electrochemical biosensing with cell culture in microfluidic devices with improved sensitivity and performance are the future of 3D systems. Particularly in cancer, such models with integrated sensing capabilities can be crucial to assess the multiple parameters involved in tumour formation, proliferation, and invasion. In this review, we are focusing on existing 3D cell culture systems with integrated electrochemical sensing for potential applications in cancer models to advance diagnosis and treatment. We discuss their design, sensing principle, and application in the biomedical area to understand the potential relevance of miniaturized electrochemical hybrid systems for the next generation of diagnostic platforms for precision medicine.
目前，传统的临床前体外研究主要基于二维（2D）细胞培养模型，这些模型在模拟真实的三维（3D）生理条件、细胞异质性、细胞间相互作用以及活组织中存在的细胞外基质（ECM）方面通常存在局限性。传统上，动物模型用于模拟组织和器官的3D环境，但它们成本高昂、耗时，引发伦理问题，并且与人体相比仍存在许多差异。基于微流控的3D细胞培养模型的应用具有优势且很有用，因为它们包括3D多细胞模型系统（MCMS）。这些模型已显示出以相对低成本和高通量模拟体内3D微环境的潜力。还探索了在MCMS中加入监测功能，以实时评估系统的生物物理和化学参数，例如温度、氧气、pH值和代谢物。电化学传感被认为是生物传感应用中最灵敏且商业适应性最强的技术之一。将电化学生物传感与微流控设备中的细胞培养相结合，提高灵敏度和性能，是3D系统的未来发展方向。特别是在癌症领域，这种具有集成传感功能的模型对于评估肿瘤形成、增殖和侵袭所涉及的多个参数可能至关重要。在这篇综述中，我们重点关注现有的具有集成电化学传感功能的3D细胞培养系统在癌症模型中的潜在应用以推动诊断和治疗。我们讨论它们的设计、传感原理以及在生物医学领域的应用，以了解小型化电化学混合系统与下一代精准医学诊断平台的潜在相关性。
