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Enhancing single-cell encapsulation in droplet microfluidics with fine-tunable on-chip sample enrichment

Microsystems & Nanoengineering 2024年第1期10卷 149-160页

作者： Tao Tang Hao Zhao Shaofei Shen Like Yang chwee teck lim Department of Biomedical Engineering National University of Singapore117583 SingaporeSingapore Integrative Sciences and Engineering Programme NUS Graduate SchoolNational University of Singapore119077 SingaporeSingapore Shanxi Key Lab for Modernization of TCVM College of Life ScienceShanxi Agricultural UniversityTaiguShanxi 030801China Institute for Health Innovation&Technology National University of Singapore117599 SingaporeSingapore Mechanobiology Institute National University of Singapore117411 SingaporeSingapore Institute for Digital Molecular Analytics and Science Nanyang Technological University636921 SingaporeSingapore

Single-cell encapsulation in droplet microfluidics is commonly hindered by the tradeoff between cell suspension density and on-chip focusing *** this study,we introduce a novel droplet microfluidic chip to overcome this *** chip comprises a double spiral focusing unit,a flow resistance-based sample enrichment module with fine-tunable outlets,and a crossflow droplet generation *** a low-density cell/bead suspension(2×10^(6) objects/mL),cells/beads are focused into a near-equidistant linear arrangement within the double spiral *** excess water phase is diverted while cells/beads remain focused and sequentially encapsulated in individual *** performance was assessed through numerical simulations and experiments at three flow rates(40,60,80μL/min),demonstrating successful focusing at 40 and 80μL/min for beads and cells,*** addition,both simulation and experimental results revealed that the flow resistance at the sample enrichment module is adjustable by punching different outlets,allowing over 50%of the aqueous phase to be ***8n-based droplet detection algorithms realized the counting of cells/beads in droplets,statistically demonstrating single-cell and bead encapsulation rates of 72.2%and 79.2%,*** the results indicate that this on-chip sample enrichment approach can be further developed and employed as a critical component in single-cell encapsulation in water-in-oil droplets.

关键词： beads outlet sample

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Cell biomechanics and its applications in human disease diagnosis

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Acta Mechanica Sinica 2015年第2期31卷 268-273页

作者： Yasaman Nematbakhsh chwee teck lim NUS Graduate School for Integrative Sciences and Engineering Department of Biomedical Engineering National University of Singapore Department of Mechanical Engineering National University of Singapore Mechanobiology Institute National University of Singapore

Certain diseases are known to cause changes in the physical and biomechanical properties of *** include cancer,malaria,and sickle cell anemia among ***,such physical property changes can result in several fold increases or decreases in cell stiffness,which are significant and can result in severe pathology and eventual catastrophic breakdown of the bodily *** there are developed biochemical and biological assays to detect the onset or presence of diseases,there is always a need to develop more rapid,precise,and sensitive methods to detect and diagnose *** property changes can play a significant role in this *** such,research into disease biomechanics can not only give us an in-depth knowledge of the mechanisms underlying disease progression,but can also serve as a powerful tool for detection and *** article provides some insights into opportunities for how significant changes in cellular mechanical properties during onset or progression of a disease can be utilized as useful means for detection and *** will also showcase several technologies that have already been developed to perform such detection and diagnosis.

关键词： Biophysical properties Cancer Malaria Cell enrichment Phenotyping Diagnostic tool Mechanopathology Cell separation and capture

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Matrisomal genes in squamous cell carcinoma of head and neck influence tumor cell motility and response to cetuximab treatment

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Cancer Communications 2022年第4期42卷 355-359页

作者： Kah Yee Goh Kah Weng Lau Terence You De Cheng Su Chin Tham chwee teck lim Narayanan Gopalakrishna Iyer Su Bin lim Darren Wan-teck lim Division of Medical Oncology National Cancer Centre SingaporeSingapore 169610 Department of Pathology National University HospitalSingapore 119074 A*STAR ProteosInstitute of Molecular and Cell BiologySingapore 138673 Department of Biomedical Engineering Mechanobiology InstituteNational University of SingaporeT-LabSingapore 117411 Institute for Health Innovation and Technology(iHealthtech) National University of SingaporeMD6Singapore 117599 Department of Head and Neck Surgery National Cancer Centre Singapore11 Hospital CrescentSingapore 169610 Office of Academic and Clinical Development Duke-NUS Medical SchoolSingapore 169857 Department of Biochemistry and Molecular Biology Ajou University School of MedicineYeongtong-GuSuwon 16499South Korea

Dear Editor,Head and neck squamous cell carcinoma(HNSCC)is the sixth most common cancer globally[1,2].Despite the improvement in treatment modalities,up to 50%of HNSCC patients still develop recurrent/metastatic(R/M)disease[3],and platinum-based chemotherapy with cetuximab and/or pembrolizumab has become the standard of care[4].However,R/M HNSCC is challenging to treat,the prognosis is poor,and there is an unmet need for new therapeutic targets.

关键词： chemotherapy cetuximab treatment

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Preface:molecular,cellular,and tissue mechanobiology

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Acta Mechanica Sinica 2017年第2期33卷 219-221页

作者： Xi-Qiao Feng Peter Vee Sin Lee chwee teck lim Institute of Biomechanics and Medical Engineering Department of Engineering MechanicsTsinghua University Department of Mechanical Engineering University of Melbourne Department of Mechanical Engineering and Mechanobiology Institute National University of Singapore

Mechanics plays a crucial role in a diversity of biological processes at different length(from molecules,cells,tissues,organs to organisms)and time *** a rapidly growing field across the interfaces of mechanics,biology,and medical engineering,mechanobiology aims to identify the mechanical and biological responses of cells and tissues of

关键词： cell ECM Preface:molecular,cellular,and tissue mechanobiology

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Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

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Bioactive Materials 2023年第6期24卷 387-400页

作者： Yufeng Shou Ling Liu Qimin Liu Zhicheng Le Khang Leng Lee Hua Li Xianlei Li Dion Zhanyun Koh Yuwen Wang Tong Ming Liu Zheng Yang chwee teck lim Christine Cheung Andy Tay Department of Biomedical Engineering National University of Singapore117583Singapore Institute for Health Innovation&Technology National University of Singapore117599Singapore School of Civil Engineering and Architecture Wuhan University of Technology430070WuhanChina NUS Tissue Engineering Program National University of Singapore117510Singapore Lee Kong Chian School of Medicine Nanyang Technological University636921Singapore School of Mechanical and Aerospace Engineering Nanyang Technological University639798Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)138648Singapore Department of Orthopaedic Surgery Yong Loo Lin School of MedicineNational University of Singapore119288Singapore Mechanobiology Institute National University of Singapore117411Singapore

Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory *** cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers,but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected in *** overcome these challenges,in this work,we describe a 3D dynamic hydrogel using magneto-stimulation for direct MSC manufacturing to *** our technology,we found that dynamic mechanical stimulation(DMS)enhanced matrix-integrinβ1 interactions which induced MSCs spreading and *** addition,DMS could modulate MSC biofunctions including directing MSC differentiation into specific lineages and boosting paracrine activities(e.g.,growth factor secretion)through YAP nuclear localization and FAK-ERK *** our magnetic hydrogel,complex procedures from MSC manufacturing to final clinical use,can be integrated into one single platform,and we believe this‘all-in-one’technology could offer a paradigm shift to existing standards in MSC therapy.

关键词： Mesenchymal stem cell Dynamic mechanical stimulation Magnetic hydrogel Stem cell manufacturing Cell therapy

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Mechanopathology of red blood cell diseases—Why mechanics matters

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Theoretical & Applied Mechanics Letters 2011年第1期1卷 1-6页

作者： chwee teck lim Mechanobiology Institute National University of Singapore Division of Bioengineering and Department of Mechanical Engineering National University of Singapore Singapore-MIT Alliance for Research & Technology(SMART)

During the onset of a disease a cell may experience alterations in both the composition and organization of its cellular and molecular *** alterations may eventually lead to changes in its geometrical and mechanical properties such as cell size and shape,deformability and *** such,knowing how diseased cells respond to mechanical forces can reveal ways by which they differ from healthy ***,we will present biomechanistic insights into red blood cell related diseases that manifest mechanical property changes and how they directly contribute to the pathophysiology of *** conducting cell and molecular mechanics studies,not only can we elucidate changes in the structure-property-function relationship of diseased cells,we can also exploit the new knowledge gained to develop biomechanics based devices that may better detect and diagnose these diseases as well as help identify important biomechanical targets for possible therapeutic interventions.

关键词： human diseases pathophysiology cell mechanics single molecule biomechanics

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Functional micro‐concrete 3D hybrid structures f abricated by two‐photon polymerization

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光电工程 2017年第4期44卷 393-399,469页

作者： Yang Li Lianwei Chen Fang Kong Zuyong Wang Ming Dao chwee teck lim Fengping Li Minghui Hong National University of Singapore 4 Engineering Drive 3 Singapore 117576 Singapore State Key Laboratory of Optical Technologies for Nano-Fabrication and Micro-Engineering Institute of Optics and Electronics Chinese Academy of Sciences Chengdu 610209 China Singapore MIT Alliance Research and Technology Singapore 138602 Singapore College of Mechanical and Electrical Engineering Wenzhou University Wenzhou 325025 China

Arbitrary micro-scale three-dimensional(3D)structures fabrication is a dream to achieve many exciting goals that have been pursued for a long *** all these applications,the direct 3D printing to fabricate human organs and integrated photonic circuits are extraordinary attractive as they can promote the current technology to a new *** all the 3D printing methods available,two-photon polymerization(2PP)is very competitive as it is the unique method to achieve sub-micron resolution to make any desired tiny *** the conventional 2PP,the building block is the ***,the requirement for the building block is different for different *** is very necessary to investigate and improve the photoresist properties according to different *** this paper,we presented one hybrid method to modify the mechanical strength and light trapping efficiency of the photoresist,which transfers the photoresist into the *** micro-concrete structure can achieve±22%strength modification via a silica nano-particles *** structures doped with gold nano-particles show tunable plasmonic *** doped hybrid structure shows great potential to fabricate 3D micro-chip laser.

关键词： 3D打印光子集成电路发展现状技术创新

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Photon momentum transfer in inhomogeneous dielectric mixtures and induced tractor beams

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Light(Science & Applications) 2015年第1期4卷 394-399页

作者： Cheng-Wei Qiu Weiqiang Ding MRCMahdy Dongliang Gao Tianhang Zhang Fook Chiong Cheong Aristide Dogariu Zheng Wang chwee teck lim Department of Electrical and Computer Engineering National University of Singapore4 Engineering Drive 3Singapore 117583Singapore NUS Graduate School for Integrative Sciences and Engineering National University of Singapore28 Medical DriveSingapore 117456Singapore Physics Department Harbin Institute of TechnologyHarbin 150001China Mechanobiology Institute National University of Singapore5A Engineering Drive 1Singapore 117411Singapore CREOL The College of Optics and PhotonicsUniversity of Central Florida4000 Central Florida BoulevardOrlandoFL 32816USA Department of Electrical and Computer Engineering University of Texas at Austin2501 SpeedwayAustinTX 78712USA Department of Mechanical Engineering National University of Singapore9 Engineering Drive 1Singapore 117576Singapore

The determination of optical force as a consequence of momentum transfer is inevitably subject to the use of the proper momentum density and stress *** is imperative and valuable to consider the intrinsic scheme of photon momentum transfer,particularly when a particle is embedded in a complex dielectric ***,we consider a particle submerged in an inhomogeneous background composed of different dielectric materials,excluding coherent illumination or hydrodynamic effects.A ray-tracing method is adopted to capture the direct process of momentum transfer from the complex background medium,and this approach is validated using the modified Einstein–Laub method,which uses only the interior fields of the particle in the *** this way,debates regarding the calculation of the force with different stress tensors using exterior fields can be *** suggested interpretation supports only the Minkowski approach for the optical momentum transfer to the embedded scatterer while rejecting Peierls’s and Abraham’s approaches,though the momentum of a stably moving photon in a continuous background medium should be considered to be of the Abraham *** interpretation also provides a novel method of realizing a tractor beam for the exertion of negative force that offers an alternative to the use of negative-index materials,optical gain,or highly non-paraxial or multiple-light interference.

关键词： dielectric interface Minkowski photon momentum transfer modified Einstein–Laub method optical pulling force optical tractor beams

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A topologically substituted boron nitride hybrid aerogel for highly selective CO2 uptake

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Nano Research 2018年第12期11卷 6325-6335页

作者： R.Govindan Kutty Sivaramapanicker Sreejith Xianghua Kong Haiyong He Hong Wang Junhao Lin Kazu Suenaga chwee teck lim Yanli Zhao Wei Ji Zheng Liu Center for Programmable Materials School of Materials Sdence and EngineeringNanyang Technological UniversitySO Nanyang Avenue639798Singapore School of Materials Science and EngineeringNanyang Technological UniversitySingapore 639798Singapore Center for Advanced 2D Materials and Graphene Research Center National University of Singapore6Science Drive 2Singapore117546Singapore Biomedical Institute for Global Health Research and Technology National University of Singapore14Medical DriveSingapore 117599Singapore Department of Physics and Beijing Key Laboratory of Optoelectronic Functional Materials & Micro-Nano Devices Renmin University of ChinaBeijing 100872China National Institute of Advanced Industrial Science and Technology (AIST) AIST Central 5Tsukuba305-8565-Japan Division of Chemistry and Biological Chemistry School of Physical and Mathematical SciencesNanyang Technological University21-Nanyang LinkSingapore 637371Singapore Department of Biomedical Engineering National University of SingaporeSingapore 117543Singapore

A topologically mediated synthesis of porous boron nitride aerogel has been experimentally and theoretically investigated for carbon dioxide (CO2) uptake. Replacement of the carbon atoms in a precursor aerogel of graphene oxide and carbon nanotubes was achieved using an elemental substitution reaction, to obtain a boron and nitrogen framework. The newly prepared BN aerogel possessed a specific surface area of 716.56 m2/g and exhibited an unprecedented twentyfold increase in CO2 uptake over N2, adsorbing 100 cc/g at 273 K and 80 cc/g in ambient conditions, as verified by adsorption isotherms via the multipoint Brunauer-Emmett-Teller (BET) method. Density functional theory calculations were performed to give hints on the mechanism of such high selectivity of CO2 over N2 adsorption in BN aerogel, which may be due to the interaction between the intrinsic polar nature of B–N bonds and the high quadrupole moment of CO2 over N2.

关键词： boron nitride boron nitride nanotube aerogel quadrupole moment selective CO 2 adsorption

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Soft tubular micro-fluidics and the application in cell sorting and wearable sensors

Soft tubular micro-fluidics and the application in cell sort...

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第十二届全国生物力学学术会议暨第十四届全国生物流变学学术会议

作者： Xiaobo Gong chwee teck lim Shanghai Jiao Tong University National University of Singapore

Objective A breakthrough of fabricating microfluidic device is required for overcoming the technological barriers in the advanced applications, such as controlling flow with multi-layer microfluidics, organ-on-chips, blood flow friendly chips etc, assocated with conventional fabricating method. Methods By controlling the curing of PDMS at the triple point of a hot mental wire, the cured and un-curved PDMS around the wire, and the heated

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