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Browsing by Subject "Acoustofluidics"
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Item Acoustofluidic Assembly of 3D Neurospheroids to Model Alzheimer’s Disease(Royal Society of Chemistry, 2020-09-28) Cai, Hongwei; Ao, Zheng; Hu, Liya; Moon, Younghye; Wu, Zhuhao; Lu, Hui-Chen; Kim, Jungsu; Guo, Feng; Medical and Molecular Genetics, School of MedicineNeuroinflammation plays a central role in the progression of many neurodegenerative diseases such as Alzheimer's disease, and challenges remain in modeling the complex pathological or physiological processes. Here, we report an acoustofluidic method that can rapidly construct 3D neurospheroids and inflammatory microenvironments for modeling microglia-mediated neuroinflammation in Alzheimer's disease. By incorporating a unique contactless and label-free acoustic assembly, this cell culture platform can assemble dissociated embryonic mouse brain cells into hundreds of uniform 3D neurospheroids with controlled cell numbers, composition (e.g. neurons, astrocytes, and microglia), and environmental components (e.g. amyloid-β aggregates) in hydrogel within minutes. Moreover, this platform can maintain and monitor the interaction among neurons, astrocytes, microglia, and amyloid-β aggregates in real-time for several days to weeks, after the integration of a high-throughput, time-lapse cell imaging approach. We demonstrated that our engineered 3D neurospheroids can represent the amyloid-β neurotoxicity, which is one of the main pathological features of Alzheimer's disease. Using this method, we also investigated the microglia migratory behaviors and activation in the engineered 3D inflammatory microenvironment at a high throughput manner, which is not easy to achieve in 2D neuronal cultures or animal models. Along with the simple fabrication and setup, the acoustofluidic technology is compatible with conventional Petri dishes and well-plates, supports the fine-tuning of the cellular and environmental components of 3D neurospheroids, and enables the high-throughput cellular interaction investigation. We believe our technology may be widely used to facilitate 3D in vitro brain models for modeling neurodegenerative diseases, discovering new drugs, and testing neurotoxicity.Item Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy(BMC, 2023-02-04) Wu, Zhuhao; Ao, Zheng; Cai, Hongwei; Li, Xiang; Chen, Bin; Tu, Honglei; Wang, Yijie; Lu, Rongze Olivia; Gu, Mingxia; Cheng, Liang; Lu, Xin; Guo, Feng; Medicine, School of MedicineCancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses for adjuvant therapy, it is challenging to predict an individual patient’s response to cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) for rapid and reliable evaluation of cancer immunotherapy. By using a label-free, contactless, and highly biocompatible acoustofluidic method, hundreds of cell clusters could be assembled from patient primary breast tumor dissociation within 2 min. Through the incorporation of time-lapse living cell imaging, the POCCs could faithfully recapitulate the cancer-immune interaction dynamics as well as their response to checkpoint inhibitors. Superior to current tumor organoids that usually take more than two weeks to develop, the POCCs can be established and used for evaluation of cancer immunotherapy within 12 h. The POCCs can preserve the cell components from the primary tumor due to the short culture time. Moreover, the POCCs can be assembled with uniform fabricate size and cell composition and served as an open platform for manipulating cell composition and ratio under controlled treatment conditions with a short turnaround time. Thus, we provide a new method to identify potentially immunogenic breast tumors and test immunotherapy, promoting personalized cancer therapy.Item Rapid Profiling of Tumor-Immune Interaction Using Acoustically Assembled Patient-Derived Cell Clusters(Wiley, 2022) Ao, Zheng; Wu, Zhuhao; Cai, Hongwei; Hu, Liya; Li, Xiang; Kaurich, Connor; Chang, Jackson; Gu, Mingxia; Cheng, Liang; Lu, Xin; Guo, Feng; Pathology and Laboratory Medicine, School of MedicineTumor microenvironment crosstalk, in particular interactions between cancer cells, T cells, and myeloid‐derived suppressor cells (MDSCs), mediates tumor initiation, progression, and response to treatment. However, current patient‐derived models such as tumor organoids and 2D cultures lack some essential niche cell types (e.g., MDSCs) and fail to model complex tumor‐immune interactions. Here, the authors present the novel acoustically assembled patient‐derived cell clusters (APCCs) that can preserve original tumor/immune cell compositions, model their interactions in 3D microenvironments, and test the treatment responses of primary tumors in a rapid, scalable, and user‐friendly manner. By incorporating a large array of 3D acoustic trappings within the extracellular matrix, hundreds of APCCs can be assembled within a petri dish within 2 min. Moreover, the APCCs can preserve sensitive and short‐lived (≈1 to 2‐day lifespan in vivo) tumor‐induced MDSCs and model their dynamic suppression of T cell tumor toxicity for up to 24 h. Finally, using the APCCs, the authors succesully model the combinational therapeutic effect of a multi‐kinase inhibitor targeting MDSCs (cabozantinib) and an anti‐PD‐1 immune checkpoint inhibitor (pembrolizumab). The novel APCCs may hold promising potential in predicting treatment response for personalized cancer adjuvant therapy as well as screening novel cancer immunotherapy and combinational therapy.