Browsing by Author "Chen, Bin"

Now showing 1 - 6 of 6
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    Acoustic assembly of cell spheroids in disposable capillaries
    (IOP, 2018-12) Wu, Yue; Ao, Zheng; Chen, Bin; Muhsen, Maram; Bondesson, Maria; Lu, Xiongbin; Guo, Feng; Medical and Molecular Genetics, School of Medicine
    Multicellular spheroids represent a promising approach to mimic 3D tissues in vivo for emerging applications in regenerative medicine, therapeutic screening, and drug discovery. Conventional spheroid fabrication methods, such as the hanging drop method, suffer from low-throughput, long time, complicated procedure, and high heterogeneity in spheroid size. In this work, we report a simple yet reliable acoustic method to rapidly assemble cell spheroids in capillaries in a replicable and scalable manner. Briefly, by introducing a coupled standing surface acoustic wave, we are able to generate a linear pressure node array with 300 trapping nodes simultaneously. This enables us to continuously fabricate spheroids in a high-throughput manner with minimal variability in spheroid size. In a proof of concept application, we fabricated cell spheroids of mouse embryonic carcinoma (P19) cells, which grew well and retained differentiation potential in vitro. Based on the advantages of the non-invasive, contactless and label-free acoustic cell manipulation, our method employs the coupling strategy to assemble cells in capillaries, and further advances 3D spheroid assembly technology in an easy, cost-efficient, consistent, and high-throughput manner. This method could further be adapted into a novel 3D biofabrication approach to replicate compilated tissues and organs for a wide set of biomedical applications.
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    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 Medicine
    Cancer 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.
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    Global Transcriptome Analysis of RNA Abundance Regulation by ADAR in Lung Adenocarcinoma
    (Elsevier, 2018-01) Sharpnack, Michael F.; Chen, Bin; Aran, Dvir; Kosti, Idit; Sharpnack, Douglas D.; Carbone, David P.; Mallick, Parag; Huang, Kun; Medicine, School of Medicine
    Despite tremendous advances in targeted therapies against lung adenocarcinoma, the majority of patients do not benefit from personalized treatments. A deeper understanding of potential therapeutic targets is crucial to increase the survival of patients. One promising target, ADAR, is amplified in 13% of lung adenocarcinomas and in-vitro studies have demonstrated the potential of its therapeutic inhibition to inhibit tumor growth. ADAR edits millions of adenosines to inosines within the transcriptome, and while previous studies of ADAR in cancer have solely focused on protein-coding edits, >99% of edits occur in non-protein coding regions. Here, we develop a pipeline to discover the regulatory potential of RNA editing sites across the entire transcriptome and apply it to lung adenocarcinoma tumors from The Cancer Genome Atlas. This method predicts that 1413 genes contain regulatory edits, predominantly in non-coding regions. Genes with the largest numbers of regulatory edits are enriched in both apoptotic and innate immune pathways, providing a link between these known functions of ADAR and its role in cancer. We further show that despite a positive association between ADAR RNA expression and apoptotic and immune pathways, ADAR copy number is negatively associated with apoptosis and several immune cell types' signatures.
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    High-Throughput Acoustofluidic Fabrication of Tumor Spheroids
    (RSC, 2019) Chen, Bin; Wu, Yue; Ao, Zheng; Cai, Hongwei; Nunez, Asael; Liu, Yunhua; Foley, John; Nephew, Kenneth; Lu, Xiongbin; Guo, Feng; Medical and Molecular Genetics, School of Medicine
    Three-dimensional (3D) culture of multicellular spheroids, offering a desirable biomimetic microenvironment, is appropriate for recapitulating tissue cellular adhesive complexity and revealing a more realistic drug response. However, current 3D culture methods are suffering from low-throughput, poor controllability, intensive-labor, and variation in spheroid size, thus not ready for many high-throughput screening applications including drug discovery and toxicity testing. Herein, we developed a high-throughput multicellular spheroid fabrication method using acoustofluidics. By acoustically-assembling cancer cells with low-cost and disposable devices, our method can produce more than 12 000 multicellular aggregates within several minutes and allow us to transfer these aggregates into ultra-low attachment dishes for long-term culture. This method can generate more than 6000 tumor spheroids per operation, and reduce tumor spheroid formation time to one day. Our platform has advantages in forming spheroids with high throughput, short time, and long-term effectiveness, and is easy-to-operation. This acoustofluidic spheroid assembly method provides a simple and efficient way to produce large numbers of uniform-sized spheroids for biomedical applications in translational medicine, pharmaceutical industry and basic life science research.
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    Impacts of Climate Change on Tibetan Lakes: Patterns and Processes
    (MDPI, 2018-02-26) Mao, Dehua; Wang, Zongming; Yang, Hong; Li, Huiying; Thompson, Julian R.; Li, Lin; Song, Kaishan; Chen, Bin; Gao, Hongkai; Wu, Jianguo; Earth Sciences, School of Science
    High-altitude inland-drainage lakes on the Tibetan Plateau (TP), the earth’s third pole, are very sensitive to climate change. Tibetan lakes are important natural resources with important religious, historical, and cultural significance. However, the spatial patterns and processes controlling the impacts of climate and associated changes on Tibetan lakes are largely unknown. This study used long time series and multi-temporal Landsat imagery to map the patterns of Tibetan lakes and glaciers in 1977, 1990, 2000, and 2014, and further to assess the spatiotemporal changes of lakes and glaciers in 17 TP watersheds between 1977 and 2014. Spatially variable changes in lake and glacier area as well as climatic factors were analyzed. We identified four modes of lake change in response to climate and associated changes. Lake expansion was predominantly attributed to increased precipitation and glacier melting, whereas lake shrinkage was a main consequence of a drier climate or permafrost degradation. These findings shed new light on the impacts of recent environmental changes on Tibetan lakes. They suggest that protecting these high-altitude lakes in the face of further environmental change will require spatially variable policies and management measures.
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    Impacts of Climate Change on Tibetan Lakes: Patterns and Processes
    (MDPI, 2018-02-26) Mao, Dehua; Wang, Zongming; Yang, Hong; Li, Huiying; Thompson, Julian; Li, Lin; Song, Kaishan; Chen, Bin; Gao, Hongkai; Wu, Jianguo; Earth Sciences, School of Science
    High-altitude inland-drainage lakes on the Tibetan Plateau (TP), the earth’s third pole, are very sensitive to climate change. Tibetan lakes are important natural resources with important religious, historical, and cultural significance. However, the spatial patterns and processes controlling the impacts of climate and associated changes on Tibetan lakes are largely unknown. This study used long time series and multi-temporal Landsat imagery to map the patterns of Tibetan lakes and glaciers in 1977, 1990, 2000, and 2014, and further to assess the spatiotemporal changes of lakes and glaciers in 17 TP watersheds between 1977 and 2014. Spatially variable changes in lake and glacier area as well as climatic factors were analyzed. We identified four modes of lake change in response to climate and associated changes. Lake expansion was predominantly attributed to increased precipitation and glacier melting, whereas lake shrinkage was a main consequence of a drier climate or permafrost degradation. These findings shed new light on the impacts of recent environmental changes on Tibetan lakes. They suggest that protecting these high-altitude lakes in the face of further environmental change will require spatially variable policies and management measures.