研究成果

代表性论文

完整的论文列表请见本页末尾。

StratoLAMP: Label-free, multiplex digital loop-mediated isothermal amplification based on visual stratification of precipitate

针对传统核酸检测依赖复杂荧光标记的局限性,我们开发了基于沉淀信号的StratoLAMP新技术,通过优化等温扩增体系使不同核酸靶标产生差异化沉淀,结合深度学习图像分析实现多靶标同步无标记检测,实验证实其可精准定量双靶标,该技术摆脱了荧光依赖,显著降低成本并简化操作,为资源有限地区的核酸检测提供了更便捷的解决方案。

Meichi Jin,# Jingyi Ding,# Yu Zhou, Jiazhao Chen, Yi Wang, and Zida Li*

Proc. Natl. Acad. Sci. U.S.A., 121(2), e2314030121, 2024

CoID-LAMP: Color-encoded, intelligent digital LAMP for multiplexed nucleic acid quantification

针对现有荧光探针法在多重核酸检测中存在的靶标特异性强、优化困难等问题,本研究开发了基于颜色编码的智能数字环介导等温扩增技术(CoID-LAMP)。该技术通过将不同染料标记的引物液滴与样本液滴在微孔阵列中配对进行LAMP扩增,利用液滴颜色解码引物信息,并通过检测扩增沉淀产物实现靶标定性与定量分析。研究首先建立了基于深度学习的图像分析流程,验证了核酸定量性能;随后分别采用荧光染料和明场染料实现了8重和4重核酸检测,证实该方法仅需普通光学成像即可完成多重检测。CoID-LAMP结合液滴微流控的多重检测优势与深度学习智能图像分析能力,为多重核酸检测提供了实用工具。

Kai Wu,# Qi Fang,# Zhantao Zhao, and Zida Li*

Anal. Chem. 95(11), 5069–5078 (2023)

Combinatorial perturbation sequencing on single cells using microwell-based droplet random pairing

针对组合药物筛选面临的高通量测试难题和现有表型分析策略的局限性,本研究开发了基于微孔液滴随机配对的单细胞组合扰动测序技术(CP-seq)。该技术通过寡核苷酸条形码标记药物分子,将药物液滴与细胞液滴在微孔阵列芯片上随机配对,实现组合药物处理与条形码标记,随后通过单细胞RNA测序同时解析细胞转录组和药物处理信息。微流控液滴操作表现出色,微孔利用率高达83%。研究通过单药处理和组合药物处理实验验证了CP-seq在药物扰动转录组采集与分析方面的能力。该技术充分发挥液滴微流控的大规模并行处理优势,为高通量组合药物筛选提供了强有力的技术手段。

Run Xie,# Yang Liu,# Shiyu Wang, Xuyang Shi, Zhantao Zhao, Longqi Liu, Ya Liu,* and Zida Li*

Biosens. Bioelectron. 220, 114913 (2023)

deep-dLAMP: deep learning-enabled polydisperse emulsion-based digital loop-mediated isothermal amplification

本研究开发了一种基于深度学习的非均匀乳液数字环介导等温扩增技术(deep-dLAMP),为核酸绝对定量提供了低成本、免标记的创新解决方案。针对传统数字核酸检测依赖精密仪器生成均一微滴和荧光检测的局限性,该技术通过在非均匀乳液中完成LAMP扩增反应,利用深度学习算法分析扩增沉淀产物图像,精准识别每个乳液的体积和阳性状态,再结合泊松分布实现核酸绝对定量。实验表明,deep-dLAMP检测限达5.6拷贝/微升,动态范围覆盖37.2-11000拷贝/微升,且对涡旋时间和图像质量等参数变化具有良好鲁棒性。该技术通过采用先进深度学习模型显著降低了仪器成本,为生物医学实验室提供了易于实施的数字化核酸检测方案,并有望发展成为即时检测系统。

Linzhe Chen,# Jingyi Ding,# Hao Yuan, Chi Chen,* and Zida Li*

Adv. Sci. 9(9), 2105450 (2022)

Point-of-care blood coagulation assay based on dynamic monitoring of blood viscosity using droplet microfluidics

本研究开发了一种基于微流控技术的凝血功能快速检测新方法,解决了传统凝血检测耗时长、样本量大且依赖大型仪器的问题。该技术通过微流控芯片自动生成血液与缓冲液的混合液滴,利用凝血过程中血液黏度变化导致的液滴颜色改变来实时监测凝血过程。研究人员建立了血液黏度与液滴颜色的定量关系,并通过实验验证了检测结果的可靠性。进一步研发的便携式检测仪原型机采用简易流体驱动系统和低成本成像模块,实现了与传统方法相当的检测性能。这项技术操作简便、成本低廉,有望发展成为具有重要临床应用价值的床旁凝血检测系统。

Linzhe Chen, Donghao Li, Xinyu Liu, Yihan Xie, Jieying Shan, Haofan Huang, Xiaxia Yu, Yudan Chen, Weidong Zheng, and Zida Li*

ACS Sens. 7(8), 2170–2177 (2022)

 

专利

Zida Li, Tao Wang, Yongjin Zhou, Zengtong Chen
A system and method for single cell isolation using droplet microfluidics
China Invention Patent Provisional Application, CN113477282A (2021)

Zida Li, Jingyi Ding, Linzhe Chen, Chi Chen
A nucleic acid quantification method based on non-uniform droplets and image analysis
China Invention Patent Provisional Application, CN114540469A (2022)

Zida Li, Qi Fang, Yujun Chai, Xiaoxiang Hu
A Droplet Digital Enzyme-Linked Immunosorbent Assay Method, Device, and Related Medium
China Invention Patent Application, ZL202410149722.7 (2024)

Zida Li, Donghao Li, Yujuan Chai, Xinyu Liu, Weidong Zheng
A detection system and method for point-of-care blood clotting function assessment
China Invention Patent Application, ZL202111620552.9 (2025)

Zida Li, Linzhe Chen, Weidong Zheng, Jieying Shan, Yihan Xie, Xinyu Liu
A device and method for the assessement of blood viscosity using microfluidics
China Invention Patent Application, ZL202110639057.6 (2021)

Zida Li, Meichi Jin, Jingyi Ding, Yi Wang, Yu Zhou
The Multiplex Nucleic Acid Quantification Method, Device, and Medium Based on Precipitation Bright Field Image Processing
China Invention Patent Application, ZL202310028332.X (2022)

Zida Li, Zhantao Zhao
An image-activated picoinjection method, system, and equipment
China Invention Patent Application, ZL202211449260.8 (2023)

Zida Li, Qi Fang, Kai Wu
Method, device, and medium for multiple digital detection of nucleic acid with deep learning
China Invention Patent Application, ZL202211516857.X (2023)

Zida Li, Xiaxia Yu, Xinyu Liu, Jieying Shan, Yihan Xie
Simulation system and method of in vitro diagnostics
China Invention Patent Application, ZL202110750662.0 (2023)

Zida Li, Lanzhu Huang, Weidong Zheng
A fabrication method and application of soft post rings for clot retraction testing
China Invention Patent Application, ZL202010260648.8 (2022)

Jianping Fu, Kevin Ward, Zida Li, Xiang Li
A microscale device for blood coagulation assay
U.S. Patent Application, 62/304,385 (2018)

Ho Cheung Shum, Alban Sauret, Zida Li, Yang Song
System and method for generation of emulsions with low interfacial tension and measuring frequency vibrations in the system
U.S. Patent Application, 13/839,072 (2013)

完整论文列表

Flow-LAMP: Label-free Digital LAMP using Scatter-based Flow Cytometry on Vortex-Generated Polydisperse Gel Beads
Wanjun Yao, Weidong Zheng, Zida Li, et al.
In Preparation

Precipitate-informed deep learning enables label-free multiplex digital nucleic acid testing in polydisperse droplets
Jiazhao Chen, Jingyi Ding, Rui Deng, Meichi Jin, Yi Wang, Zida Li, et al.
In Preparation

Materials-Driven Innovations in Digital Nucleic Acid Amplification Technologies: Transforming Molecular Diagnostics
Jiazhao Chen, Kai Wu, Jingyi Ding, Zida Li, et al.
In Revision

Reimagining POCT assays: Automated digital microfluidics for multiplex in vitro diagnostics
Wenkai Fan, Donghao Li, Jingyi Ding, Zida Li*
Talanta, in press (2025)

Droplet digital PCR-based single aptamer selection
Zerui Wu,# Wanjun Yao,# Jinyu Chen, Yonghao Chen, Zida Li, Weiping Ding,* Liqun He,* and Peng Hu*
Talanta, 127924 (2025)

Embracing Poisson encapsulation statistics for improved droplet digital immunoassay
Yujuan Chai, Xiaoxiang Hu, Qi Fang, Yuanyuan Guo, Binmao Zhang, Hangjia Tu, and Zida Li*
Anal. Chem. 97(1), 444–453 (2025)

StratoLAMP: Label-free, multiplex digital loop-mediated isothermal amplification based on visual stratification of precipitate
Meichi Jin,# Jingyi Ding,# Yu Zhou, Jiazhao Chen, Yi Wang, and Zida Li*
Proc. Natl. Acad. Sci. U.S.A., 121(2), e2314030121, 2024

Image-activated pico-injection for single cell analysis
Zhantao Zhao, Heng Zhai, Peng Zuo, Tao Wang, Run Xie, Mu Tian, Ruyuan Song, Xiaonan Xu, and Zida Li*
Talanta 272, 125765 (2024)

CoID-LAMP: Color-encoded, intelligent digital LAMP for multiplexed nucleic acid quantification
Kai Wu,# Qi Fang,# Zhantao Zhao, and Zida Li*
Anal. Chem. 95(11), 5069–5078 (2023)

Combinatorial perturbation sequencing on single cells using microwell-based droplet random pairing
Run Xie,# Yang Liu,# Shiyu Wang, Xuyang Shi, Zhantao Zhao, Longqi Liu, Ya Liu,* and Zida Li*
Biosens. Bioelectron. 220, 114913 (2023)

High resolution, multiplex antibody patterning using micropillar-focused droplet printing and microcontact printing
Meichi Jin, Kai Wu, Mengzhen Wang, Yang Zhang, Chengbin Yang, and Zida Li*
Adv. Biol. 7(8), 2300111 (2023)

Bone-on-a-chip platforms and integrated biosensors: towards advanced in vitro bone models with real-time biosensing
Yang Zhang, Taozhao Yu, Jingyi Ding, and Zida Li*
Biosens. Bioelectron. 219, 114798 (2023)

deep-dLAMP: deep learning-enabled polydisperse emulsion-based digital loop-mediated isothermal amplification
Linzhe Chen,# Jingyi Ding,# Hao Yuan, Chi Chen,* and Zida Li*
Adv. Sci. 9(9), 2105450 (2022)

Point-of-care blood coagulation assay based on dynamic monitoring of blood viscosity using droplet microfluidics
Linzhe Chen, Donghao Li, Xinyu Liu, Yihan Xie, Jieying Shan, Haofan Huang, Xiaxia Yu, Yudan Chen, Weidong Zheng, and Zida Li*
ACS Sens. 7(8), 2170–2177 (2022)

Generation and Screening of Antigen-Specific Nanobodies from Mammalian Cells Expressing the BCR Repertoire Library Using Droplet-Based Microfluidics
Menghua Lyu,# Xuyang Shi,# Xiaopan Liu,# Yang Liu, Xijun Zhu, Lijuan Liao, Hongyan Zhao, Na Sun, Shiyu Wang, Linzhe Chen, Linyuan Fan, Qumiao Xu, Qianqian Zhu, Kai Gao, Huaying Chen, Yonggang Zhu, Zida Li, Weijin Guo, Yue Zheng, Ying Gu, Longqi Liu,* Meiniang Wang,* and Ya Liu*
Anal. Chem. 94(22), 7970–7980 (2022)

Point-of-care blood coagulation assay enabled by printed circuit board-based digital microfluidics
Donghao Li,# Xinyu Liu,# Yujuan Chai,# Jieying Shan, Yihan Xie, Yong Liang, Susu Huang, Weidong Zheng, and Zida Li*
Lab Chip 22(4), 709-716 (2022)

Single-cell sequencing to unveil the mystery of embryonic development
Zida Li,#,* Feng Lin,# Chu-Han Zhong, Shue Wang, Xufeng Xue, and Yue Shao*
Adv. Biol. 6(2), 2101151 (2022)

High-throughput functional screening of antigen-specific T-cells based on droplet microfluidics on single-cell level
Shiyu Wang,# Yang Liu,# Yijian Li, Menghua Lv, Kai Gao, Ying He, Wenbo Wei, Yonggang Zhu, Xuan Dong, Xun Xu, Zida Li,* Longqi Liu,* and Ya Liu*
Anal. Chem. 94(2), 918–926 (2022)

Emerging biosensing technologies for improved diagnostics of COVID-19 and future pandemics
Linzhe Chen, Guoliang Zhang, Longqi Liu, and Zida Li
Talanta 225, 121986 (2021)

Micro-engineered flexural post rings for effective blood sample fencing and high throughput measurement of clot retraction force
Lanzhu Huang,# Xinyu Liu,# Yuanbin Ou, Haofan Huang, Xia Zhang, Yize Wang, Yong Liang, Xiaxia Yu, Weidong Zheng, Huisheng Zhang, and Zida Li*
ACS Sens. 5(12), 3949-3955 (2020)

Recent advances in solar-driven evaporation system
Zhourui Xu, Zida Li, Yihang Jiang, Gaixia Xu, Mingwei Zhu, Wing-Cheung Law, Ken-Tye Yong, Yanshuai Wang, Chengbin Yang, Biqin Dong, and Feng Xing*
J. Mater. Chem. A 8, 25571-25600 (2020)

Stretchable supercapacitors as emergent energy storage units for health monitoring bioelectronics
Xue Chen, Nicolo Simone Villa, Yanfeng Zhuang, Linzhe Chen, Tianfu Wang, Zida Li, and Tiantian Kong
Adv. Energy Mater. 10(4), 1902769 (2020)

Dean flow assisted single cell and bead encapsulation for high performance single cell expression profiling
Luoquan Li,# Ping Wu,# Zhaofeng Luo, Lei Wang, Weiping Ding, Tao Wu, Jinyu Chen, Jinlong He, Yi He, Heran Wang, Ying Chen, Guibo Li, Zida Li,* and Liqun He*
ACS Sens. 4(5), 1299-1305 (2019)

Multiple splitting of droplets using multi-furcating microfluidic channels
Zida Li, Luoquan Li, Meixiang Liao, Liqun He, and Ping Wu
Biomicrofluidics 13(2), 024112 (2019)

Controlled modeling of human epiblast and amnion development using stem cells
Yi Zheng, Xufeng Xue, Yue Shao, Sicong Wang, Sajedeh Nasr Esfahani, Zida Li, Jonathon M. Muncie, Johnathon N. Lakins, Valerie M. Weaver, Deborah L. Gumucio, and Jianping Fu*
Nature 573(7774), 421-425 (2019)

Dorsal-ventral patterned neural cyst from human pluripotent stem cells in a neurogenic niche
Yuanyuan Zheng,# Xufeng Xue,# Agnes M. Resto Irizarry, Zida Li, Yue Shao, Yi Zheng, Gang Zhao,* and Jianping Fu*
Sci. Adv. 5(12), eaax5993 (2019)

Microengineered human amniotic ectoderm tissue array for high-content developmental phenotyping
Sajedeh Nasr Esfahani, Yue Shao, Agnes M Resto Irizarry, Zida Li, Xufeng Xue, Deborah L Gumucio, and Jianping Fu*
Biomaterials 216, 119244 (2019)

Biophysical phenotypes and determinants of anterior vs. posterior primitive streak cells derived from human pluripotent stem cells
Feng Lin, Yue Shao, Xufeng Xue, Yi Zheng, Zida Li, Chunyang Xiong, and Jianping Fu
Acta Biomater. 86, 125-134 (2019)

Carbon nanotube strain sensor based hemoretractometer for blood coagulation testing
Zida Li, Yize Wang, Xufeng Xue, Brendan McCracken, Kevin Ward, and Jianping Fu*
ACS Sens. 3(3), 670-676 (2018)

Capillary assisted deposition of carbon nanotube film for strain sensing
Zida Li, Xufeng Xue, Feng Lin, Yize Wang, Kevin Ward, and Jianping Fu*
Appl. Phys. Lett. 111(17), 173105 (2017)

Tracking the tumor invasion front using long-term fluidic tumoroid culture
Koh Meng Aw Yong, Zida Li, Sofia D. Merajver, and Jianping Fu*
Sci. Rep. 7, (2017)

Acoustic tweezing cytometry enhances osteogenesis of human mesenchymal stem cells through cytoskeletal contractility and YAP activation
Xuefeng Xue, Xiaowei Hong, Zida Li, Cheri X. Deng, and Jianping Fu*
Biomaterials 134, 22-30 (2017)

Controlled tubular unit formation from collagen film for modular tissue engineering
Jianming Sang, Xiang Li, Yue Shao, Zida Li, and Jianping Fu*
ACS Biomater. Sci. Eng. 3(11), 2860-2868 (2016)

A miniaturized hemoretractometer for blood clot retraction testing
Zida Li, Xiang Li, Brendan McCracken, Yue Shao, Kevin Ward, and Jianping Fu*
Small 12, 3926–3934 (2016)

Musical interfaces: visualization and reconstruction of music with a microfluidic two-phase flow
Sze Yi Mak, Zida Li, Arnaud Frere, Tat Chuen Chan, and Ho Cheung Shum*
Sci. Rep. 4, 6675 (2014)

Syringe-pump-induced fluctuation in all-aqueous microfluidic system implications for flow rate accuracy
Zida Li, Sze Yi Mak, Alban Sauret, and Ho Cheung Shum*
Lab Chip 14(4), 744-749 (2014)

Emerging microengineered tools for functional analysis and phenotyping of blood cells
Xiang Li, Weiqiang Chen, Zida Li, Ling Li, Hongchen Gu, and Jianping Fu*
Trends Biotechnol. 32(11), 586-594 (2014)

Dynamics for dense packing of colloids
Liqun He*, Ping Wu, Zida Li, and Lili Feng
Adv. Mater. Res. 165, 248-254 (2012)