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Mechanism of nanoparticle aggregation in gas-liquid microfluidic mixing

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Chinese Chemical Letters 2024年第4期35卷 376-381页

作者： Hongxia li Xiyang Wang Du Qiao Jiahao li Weiping Zhu honglin li Key Laboratory for Precision&Non-traditional Machining Technology of Ministry of Education Dalian University of TechnologyDalian 116023China Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghai 200237China

Using gas-liquid segmented micromixers to prepare nanoparticles that have a homogeneous particle size, controllable shape, and monodispersity advantages. Although nanoparticle aggregation within a microfluid has been shown to be affected by the shear effect, the shear effect triggering conditions in gasliquid two-phase flow is unclear and the aggregation behavior of nanoparticles under the shear effect is difficult to predict, resulting in uncontrollable physical and chemical properties of nanoparticle aggregates. In this study, a numerical simulation of nanoparticle aggregation in gas-liquid two-phase flow under the shear effect is performed using the CFD-DEM method. Then, the effects of total flow rate,gas-liquid two-phase flow ratio, and particle volume fraction on particle aggregation were analyzed to achieve control of particle aggregation shape and size. Meanwhile, the triggering mechanism of the shear effect and the mechanism of the shear effect on the aggregation of nanoparticles were clarified. The results show that increasing the total flow rate or decreasing the gas-liquid two-phase flow rate ratio can induce the shear effect, which reduces the particle aggregation size and makes the morphology tend to be spherical. Moreover, increasing the particle volume fraction, and total flow rate or decreasing the gas-liquid two-phase flow rate ratio also increases the number of particle collisions and induce interparticle adhesion. Hence, particle adhesion and the shear effect compete with each other and together affect particle aggregation.

关键词： Microfluidic Gas-liquid segmented micromixer Nanoparticle aggregation Shear effect Numerical calculation

Microfluidic separation of particles by synergistic effect of geometry-induced hydrodynamics and magnetic field

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Chinese Chemical Letters 2024年第2期35卷 380-385页

作者： Du Qiao Hongxia li Weiping Zhu lili Zhu Danyang Zhao honglin li Key Laboratory for Precision & Non-traditional Machining Technology of Ministry of Education Dalian University of TechnologyDalian 116023China Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghai 200237China lingang Lab Shanghai 200031China

Microfluidic combined with magnetic field have been demonstrated to be the promising solutions for fast and low-damage particles separation.However,the difficulties in the precise layout of magnets and accurate prediction of particle trajectories lead to under and over separation of target particles.A novel particle separation lab-on-chip(LOC)prototype integrated with microstructures and micropolar arrays is designed and characterized.Meanwhile,a numerical model for the separation of magnetic particles by the synergistic effect of geometry-induced hydrodynamics and magnetic field is constructed.The effect of geometry and magnetic field layout on particle deflection is systematically analyzed to implement accurate prediction of particle trajectories.It is found that the separation efficiency of magnetic particles increased from 50.2%to 91.7%and decreased from 88.6%to 85.7%in the range of depth factors from 15µm to 27µm and width factors from 30µm to 60µm,respectively.In particular,the combined effect of the offset distance of permanent magnets and the distance from the main flow channel exhibits a significant difference from the conventional perception.Finally,the developed LOC prototype was generalized for extension to arbitrary systems.This work provides a new insight and robust method for the microfluidic separation of magnetic particles.

关键词： Microfluidic Particle separation Synergistic effect Hydrodynamics Magnetic field Numerical calculation

A lateral-immobilization zebrafish microfluidic chip-based system for in vivo real-time evaluation of antithrombotic agents

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Chinese Chemical Letters 2024年第3期35卷 312-315页

作者： lijuan He Hongxia Du Yi Yang Zhihua Guan Jinjin li honglin li Xudong lin lili Zhu Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science&TechnologyShanghai 200237China Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument School of Biomedical EngineeringShenzhen Campus of Sun Yat-sen UniversityShenzhen 518000China Innovation Center for AI and Drug Discovery East China Normal UniversityShanghai 200062China

Thrombosis remains a major global health concern mainly characterized by high rates of morbidity and mortality.Animal models serve as an indispensable tool to understand the underlying pathogenesis of thrombosis and assess the efficacy of novel antithrombotic drugs.Currently,zebrafish has emerged as a valuable model organism for thrombosis research.However,the traditional method of studying zebrafish thrombosis requires a laborious and time-consuming procedure,including anesthesia and manual immobilization of zebrafish.In this study,based on hydrodynamic force,a lateral-immobilization zebrafish microfluidic chip(liZMC)was designed to evaluate the cardiovascular system of multiple larvae within a single microscope field of view.Specifically,coupling with microscope imaging,real-time monitoring of the peripheral blood circulation in the tail of phenylhydrazine(PHZ)-induced zebrafish thrombosis was enabled.Furthermore,the reliability of liZMC for in vivo evaluation of antithrombotic agents in zebrafish was verified using aspirin.Collectively,this novel liZMC-based system can be used for in vivo zebrafish thrombosis studies and rapid screening of antithrombotic agents.

关键词： Microfluidic chip Zebrafish Thrombosis In vivo evaluation Real-time monitor

Design,synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells

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Chinese Chemical Letters 2024年第5期35卷 287-289页

作者： Wenyi Mei lijuan Xie Xiaodong Zhang Cunjian Shi Fengzhi Wang Qiqi Fu Zhenjiang Zhao honglin li Yufang Xu Zhuo Chen Shanghai Key Laboratory of New Drug Design State Key Laboratory of Bioreactor EngineeringSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Innovation Center for AI and Drug Discovery East China Normal UniversityShanghai 200062China lingang Laboratory Shanghai 200031China

Ursolic acid(UA)is a naturally occurring ursane triterpenoid,which exhibits a wide range of unique biological activities.To clarify its mechanism of action(MOA),a series of fluorescent derivatives of UA(5a-c)were designed and synthesized by conjugation with 7-nitrobenzo-2-oxa-1,3-diazole(NBD)fluorophore.Among them,5c exhibited similar anti-proliferative activity with UA against HCT116 cells(half maximal inhibitory concentration(IC_(50))=9.21±0.50μmol/L).Cell imaging experiment indicated that 5c was rapidly taken up in HCT116 cells in a dose and time-dependent manner.Then,5c was found to localize in endoplasmic reticulum(ER),lysosomes,and mitochondria,but not in nucleus of HCT116 cells by confocal microscopy studies.Preliminary MOA proved that UA induced autophagy with a unique intracellular distribution mechanism involving ER and lysosome.In all,our work provides new clues for revealing the molecular mechanism of UA as an antitumor agent.

关键词： Pentacyclic triterpenoid Ursolic acid Fluorescent derivatives Autophagy Apoptosis

Advancements in life-on-a-chip: The impact of “Beyond limits Manufacturing” technology

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Chinese Chemical Letters 2024年第5期35卷 13-16页

作者： Weiwei He Hongbo Zhang Xudong lin lili Zhu Tingting Zheng Hao Pei Yang Tian Min Zhang Guoyue Shi Lei Wu Jianlong Zhao Gulinuer Wumaier Shengqing li Yufang Xu honglin li Xuhong Qian Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghai 200237China School of Mechanical and Power Engineering East China University of Science and TechnologyShanghai 200237China Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument School of Biomedical EngineeringShenzhen Campus of Sun Yat-sen UniversityShenzhen 518000China Shanghai Key Laboratory of Green Chemistry and Chemical Processes Department of ChemistrySchool of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China Shanghai Institute of Microsystem and Information Technology Chinese Academy of SciencesShanghai 200050China Department of Pulmonary and Critical Care Medicine Huashan HospitalFudan UniversityShanghai 200040China Innovation Center for AI and Drug Discovery East China Normal UniversityShanghai 200062China lingang Laboratory Shanghai 200031China

This review explores the concept of life-on-a-chip,which involves the creation of miniaturized biological systems,such as organs,tissues,and model organisms,on microscale platforms called microfluidic chips.These chips consist of intricately etched channels,wells,and chambers that enable precise control and observation of fluids,cells,and biochemical reactions,facilitating the simulation of various aspects of human or animal physiology and the study of responses to different stimuli,drugs,or disease conditions.The review highlights the application of a novel technology,“Beyond limit Manufacturing”(BLM),in the development of sophisticated three-dimensional cell models and model organism microchips.Modelorganism-on-a-chip and organ-on-a-chip(OoC)are among the thriving developments in the field of microfluidics,allowing for the reconstruction of living microenvironments and implementation of multiple stimuli.The review discusses the latest advancements in life-on-a-chip technology using BLM and outlines potential future research directions,emphasizing the significant role of these chips in studying complex biological processes in a controlled and scalable manner.

关键词： Beyond limit Manufacturing Model-organism-on-a-chip Organ-on-a-chip

Biomimetic“Gemini nanoimmunoregulators”orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1345-1361页

作者： honglin Huang Ningxi li Xiaodan Wei Qingzhi li Junhan Guo Geng Yang Hong Yang Lulu Cai Yiyao liu Chunhui Wu Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People’s Hospitaland School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengdu 610054China TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)degradation.The“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 peptides.mPDA/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity.Meanwhile,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes.This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis.This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

关键词： Biomimetic immunoregulator Spatiotemporal delivery Targeted photothermal therapy Amplified immunogenic cell death Immunosuppressive tumor microenvironment PD-L1 degradation TAMs phenotype reversion Metastasis inhibition

Single-atom alloys prepared by two-step thermal evaporation

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Nano Research 2024年第4期17卷 2808-2813页

作者： honglin Wang Jing li Meirong Huang Jizhe Cui Zhiying Cheng Rong Yu Hongwei Zhu State Key Lab of New Ceramics and Fine Processing School of Materials Science and EngineeringTsinghua UniversityBeijing 100084China State Key Lab of Solid Waste Reuse for Building Materials Beijing Building Materials Academy of Science ResearchBeijing 100041China

Single-atom alloys(SAAs)have gained significant attention due to their remarkable atomic utilization efficiency,interactions between single atoms(SAs)and metal supports,and free-atom-like electronic structure of dopant elements.In this work,we observed the formation of SAs in pre-deposited metal particles by a two-step thermal evaporation technique,thereby establishing the first instance of discovering SAAs by thermal evaporation.The discovery of SAAs by thermal evaporation extends the range of SAAs preparation methods to include this traditional synthetic technique,which offers convenience,cost-efficiency,and universality.The formation mechanism of SAAs prepared using this technique was elucidated by density functional theory calculations.It was demonstrated that thermal evaporation can be utilized to prepare SAAs with multiple SAs,further highlighting its universal applicability.

关键词： single-atom alloys thermal evaporation density functional theory

Long distance all-optical logic operations through a single multimode fiber empowered by wavefront shaping

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Photonics Research 2024年第3期12卷 587-597页

作者： ZHIPENG YU TIANTING ZHONG HUANHAO li HAORAN li CHI MAN WOO SHENGFU CHENG SHUMING JIAO honglin liU CHAO LU PUXIANG LAI Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHong Kong SARChina Hong Kong Polytechnic University Shenzhen Research Institute Shenzhen 518000China Peng Cheng Laboratory Shenzhen 518055China Key Laboratory for Quantum Optics Shanghai Institute of Optics and Fine MechanicsChinese Academy of SciencesShanghai 201800China Department of Electronic and Information Engineering The Hong Kong Polytechnic UniversityHong Kong SARChina Photonics Research Institute The Hong Kong Polytechnic UniversityHong Kong SARChina

Multimode fibers(MMFs)are a promising solution for high-throughput signal transmission in the time domain.However,crosstalk among different optical modes within the MMF scrambles input information and creates seemingly random speckle patterns at the output.To characterize this process,a transmission matrix(TM)can be used to relate input and output fields.Recent innovations use TMs to manipulate the output field by shaping the input wavefront for exciting advances in deep-brain imaging,neuron stimulation,quantum networks,and analog operators.However,these approaches consider input/output segments as independent,limiting their use for separate signal processing,such as logic operations.Our proposed method,which makes input/output segments as interdependent,adjusts the phase of corresponding output fields using phase bias maps superimposed on input segments.Coherent superposition enables signal logic operations through a 15-m-long MMF.In experiments,a single optical logic gate containing three basic logic functions and cascading multiple logic gates to handle binary operands is demonstrated.Bitwise operations are performed for multi-bit logic operations,and multiple optical logic gates are reconstructed simultaneously in a single logic gate with polarization multiplexing.The proposed method may open new avenues for long-range logic signal processing and transmission via MMFs.

关键词： optical polarization fiber

A Transient-Pressure-Based Numerical Approach for Interlayer Identification in Sand Reservoirs

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Fluid Dynamics & Materials Processing 2024年第3期20卷 641-659页

作者： Hao Luo Haibo Deng honglin Xiao Shaoyang Geng Fu Hou Gang Luo Yaqi li Tight Oil and Gas Exploration and Development Project Department PetroChina Southwest Oil and Gas Field CompanyChengdu610051China Energy College Chengdu University of TechnologyChengdu610059China

Almost all sandstone reservoirs contain interlayers. The identification and characterization of these interlayers iscritical for minimizing the uncertainty associated with oilfield development and improving oil and gas recovery.Identifying interlayers outside wells using identification methods based on logging data and machine learning isdifficult and seismic-based identification techniques are expensive. Herein, a numerical model based on seepageand well-testing theories is introduced to identify interlayers using transient pressure data. The proposed modelrelies on the open-source MATLAB Reservoir Simulation Toolbox. The effects of the interlayer thickness, position,and width on the pressure response are thoroughly investigated. A procedure for inverting interlayer parametersin the reservoir using the bottom-hole pressure is also proposed. This method uses only transient pressuredata during well testing and can effectively identify the interlayer distribution near the wellbore at an extremelylow cost. The reliability of the model is verified using effective oilfield examples.

关键词： Sand reservoir interlayer identification transient pressure analysis numerical well test