Qin Yanzhe, Koehler Stephan A, Ling Yunyan, Yu Shiqiang, Zhang Yongjie, Luo Jie, Chen Kaijian, Junjie Luo, Zeng Junjie, Chu Haiyang, Wang Fei, Li Wei, Li Dan, Yu Xinran, Wu Xiangchao, Zhao Shengming, Lu Hao, Deng Ziqing, Yang Zhijian, Mai Ruibin, Liu Zhuo, Niu Zihua, Huang Xin, Xing Chengmei, Zhang Xingcai, Hu Yongyou, Peng Xinwen, Liao Xiaoxing, Qu Xiangmeng, Gong Yiming, Chen Qiushui, Hermans Thomas M, Zhang Wenwei, Yang Huanghao
BGI Research, Shenzhen, China.
MGI Tech, Shenzhen, China.
Nat Methods. 2025 Jul 14. doi: 10.1038/s41592-025-02730-2.
Next-generation sequencing (NGS) technologies have achieved remarkable success in both biological research and clinical applications. However, in recent years, performance improvements have slowed due to fundamental limitations imposed by Poiseuille fluid dynamics in flow cells, which we overcome using Couette flow. Here we show NGS by roll-to-roll fluidics (r2r-fl), a cost-effective approach compatible with flexible biochip sizes. r2r-fl is a practical implementation of plane Couette flow, with up to 85-fold lower reagent consumption (US$0.16 per gigabase pair), rinsing times under 2 s and a reduction in paired-end 100-base pair sequencing turnaround from days to less than 12 h. The method maintains over 99.9% precision and 99.3% sensitivity of single nucleotide polymorphisms in the human genome, 99.9% mapping rate for Escherichia coli, and minimal nucleotide substitutions, deletions or insertions in the severe acute respiratory syndrome coronavirus 2 alpha strain. By lowering cost and time, r2r-fl enables rapid, scalable NGS for pathogen detection, cancer diagnostics and genetic disease profiling.
下一代测序（NGS）技术在生物学研究和临床应用方面都取得了显著成功。然而，近年来，由于流动池中的泊肃叶流体动力学带来的基本限制，性能提升速度放缓，我们利用库埃特流克服了这一问题。在此，我们展示了基于卷对卷流体技术（r2r-fl）的下一代测序，这是一种与灵活的生物芯片尺寸兼容的经济高效方法。r2r-fl是平面库埃特流的实际应用，试剂消耗量降低了85倍（每千兆碱基对0.16美元），冲洗时间不到2秒，双端100碱基对测序周转时间从数天缩短至不到12小时。该方法在人类基因组中保持了单核苷酸多态性超过99.9%的精度和99.3%的灵敏度，对大肠杆菌的映射率为99.9%，在严重急性呼吸综合征冠状病毒2α毒株中核苷酸替换、缺失或插入极少。通过降低成本和时间，r2r-fl能够实现用于病原体检测、癌症诊断和遗传疾病分析的快速、可扩展的下一代测序。
