Microstructure-based techniques for single-cell manipulation and analysis

Abstract Over the past few years, manipulating and analyzing methods based on single-cell level have become frequently adopted to conduct the cell heterogeneity study (e.g., differentiation of stem cells, tumor cell heterogeneity). Traditional single-cell analysis techniques exhibit high processing complexity and time-consuming characteristic, and require expensive equipment, considerably limiting their applications in cellular heterogeneity study. Microfluidics-based systems to conduct single-cell study have appeared to be powerful methods as fueled with the advancement of microfluidics techniques. This paper reviews microstructure-based methods for single-cell manipulation and analysis. The methods based on microvalve for single-cell manipulation are also discussed in this paper. Lastly, the challenges required to be addressed in the future are highlighted.

[1]  Jin-Ming Lin,et al.  Fabrication of microwell arrays based on two-dimensional ordered polystyrene microspheres for high-throughput single-cell analysis. , 2010, Analytical chemistry.

[2]  Stephen R Quake,et al.  Single-cell multimodal profiling reveals cellular epigenetic heterogeneity , 2016, Nature Methods.

[3]  Liang Huang,et al.  A fluidic circuit based, high-efficiency and large-scale single cell trap. , 2016, Lab on a chip.

[4]  Bo Huang,et al.  Counting Low-Copy Number Proteins in a Single Cell , 2007, Science.

[5]  Jeong-Gun Lee,et al.  SSA-MOA: a novel CTC isolation platform using selective size amplification (SSA) and a multi-obstacle architecture (MOA) filter. , 2012, Lab on a chip.

[6]  Katsuo Kurabayashi,et al.  Recent advancements in optofluidics-based single-cell analysis: optical on-chip cellular manipulation, treatment, and property detection. , 2014, Lab on a chip.

[7]  Matthew M. Crane,et al.  A Microfluidic System for Studying Ageing and Dynamic Single-Cell Responses in Budding Yeast , 2014, PloS one.

[8]  Yuliang Xie,et al.  Acoustofluidic methods in cell analysis. , 2019, Trends in analytical chemistry : TRAC.

[9]  Kai Zhang,et al.  Block-Cell-Printing for live single-cell printing , 2014, Proceedings of the National Academy of Sciences.

[10]  Ashutosh Kumar Singh,et al.  Microfluidic-based patterning of embryonic stem cells for in vitro development studies. , 2013, Lab on a chip.

[11]  Xuexia Lin,et al.  A non-invasive genomic diagnostic method for bladder cancer using size-based filtration and microchip electrophoresis. , 2015, Talanta.

[12]  Jie-Long He,et al.  Digital Microfluidics for Manipulation and Analysis of a Single Cell , 2015, International journal of molecular sciences.

[13]  Mehmet Toner,et al.  Inertial focusing in microfluidics. , 2014, Annual review of biomedical engineering.

[14]  Jinyi Wang,et al.  Deformability and size-based cancer cell separation using an integrated microfluidic device. , 2015, The Analyst.

[15]  A. Folch,et al.  3D-printed Quake-style microvalves and micropumps. , 2018, Lab on a chip.

[16]  Lidong Qin,et al.  Microfluidics separation reveals the stem-cell–like deformability of tumor-initiating cells , 2012, Proceedings of the National Academy of Sciences.

[17]  Chwee Teck Lim,et al.  Microfluidic cell trap array for controlled positioning of single cells on adhesive micropatterns. , 2013, Lab on a chip.

[18]  Fumihito Arai,et al.  Measurement of the mechanical properties of single Synechocystis sp. strain PCC6803 cells in different osmotic concentrations using a robot-integrated microfluidic chip. , 2018, Lab on a chip.

[19]  A. Levin,et al.  Observation of molecular self-assembly events in massively parallel microdroplet arrays. , 2018, Lab on a chip.

[20]  D. Janasek,et al.  A microfluidic array with cellular valving for single cell co-culture. , 2011, Lab on a chip.

[21]  Woncheol Lee,et al.  Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells , 2019, Nature Communications.

[22]  Jin‐Ming Lin,et al.  Analysis of cellular biomolecules and behaviors using microfluidic chip and fluorescence method , 2019, TrAC Trends in Analytical Chemistry.

[23]  Burak Dura,et al.  Profiling lymphocyte interactions at the single-cell level by microfluidic cell pairing , 2015, Nature Communications.

[24]  Chia-Hsien Hsu,et al.  Hydrodynamic shuttling for deterministic high-efficiency multiple single-cell capture in a microfluidic chip. , 2019, Lab on a chip.

[25]  P. Black,et al.  Continuous Flow Deformability-Based Separation of Circulating Tumor Cells Using Microfluidic Ratchets. , 2016, Small.

[26]  J. Voldman,et al.  Multiparameter cell-tracking intrinsic cytometry for single-cell characterization. , 2018, Lab on a chip.

[27]  Michael E Phelps,et al.  Integrated microfluidics for parallel screening of an in situ click chemistry library. , 2006, Angewandte Chemie.

[28]  S. Vanapalli,et al.  Microfluidic bypass manometry: highly parallelized measurement of flow resistance of complex channel geometries and trapped droplets. , 2017, Lab on a chip.

[29]  A. deMello,et al.  Hydrodynamics in Cell Studies , 2018, Chemical reviews.

[30]  Hongshen Ma,et al.  Microfluidic cell-phoresis enabling high-throughput analysis of red blood cell deformability and biophysical screening of antimalarial drugs. , 2015, Lab on a chip.

[31]  D. Kohlheyer,et al.  Microbial single-cell analysis in picoliter-sized batch cultivation chambers. , 2018, New biotechnology.

[32]  Kwanghun Chung,et al.  A microfluidic array for large-scale ordering and orientation of embryos , 2010, Nature Methods.

[33]  Luke P. Lee,et al.  Single-cell level co-culture platform for intercellular communication. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[34]  Joonwon Kim,et al.  Integration of a microfluidic chip with a size-based cell bandpass filter for reliable isolation of single cells. , 2015, Lab on a chip.

[35]  Euisik Yoon,et al.  Paired single cell co-culture microenvironments isolated by two-phase flow with continuous nutrient renewal. , 2014, Lab on a chip.

[36]  Shoji Takeuchi,et al.  A trap-and-release integrated microfluidic system for dynamic microarray applications , 2007, Proceedings of the National Academy of Sciences.

[37]  Jaehoon Chung,et al.  Highly-efficient single-cell capture in microfluidic array chips using differential hydrodynamic guiding structures. , 2011, Applied physics letters.

[38]  Shoji Takeuchi,et al.  A resettable dynamic microarray device , 2011, Biomedical microdevices.

[39]  T. Schroeder,et al.  Automated Microfluidic System for Dynamic Stimulation and Tracking of Single Cells. , 2018, Analytical chemistry.

[40]  D Jin,et al.  A microfluidic device enabling high-efficiency single cell trapping. , 2015, Biomicrofluidics.

[41]  Chang-Soo Lee,et al.  On-chip analysis, indexing and screening for chemical producing bacteria in a microfluidic static droplet array. , 2016, Lab on a chip.

[42]  Jin-Ming Lin,et al.  Microfluidic technologies in cell isolation and analysis for biomedical applications. , 2017, The Analyst.

[43]  Zechen Chong,et al.  Single-cell isolation by a modular single-cell pipette for RNA-sequencing. , 2016, Lab on a chip.

[44]  Donald Wlodkowic,et al.  Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells. , 2009, Lab on a chip.

[45]  Liwei Lin,et al.  Hydrodynamic resettability for a microfluidic particulate-based arraying system. , 2012, Lab on a chip.

[46]  D. Pang,et al.  A High Throughput Micro-Chamber Array Device for Single Cell Clonal Cultivation and Tumor Heterogeneity Analysis , 2015, Scientific Reports.

[47]  Subra Suresh,et al.  A microfabricated deformability-based flow cytometer with application to malaria. , 2011, Lab on a chip.

[48]  Kun Liu,et al.  A Microfluidic Chip with Double-Slit Arrays for Enhanced Capture of Single Cells , 2018, Micromachines.

[49]  Catherine A. Rivet,et al.  Imaging single-cell signaling dynamics with a deterministic high-density single-cell trap array. , 2011, Analytical chemistry.

[50]  D. Kell,et al.  Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses. , 1996, Microbiological reviews.

[51]  Burak Dura,et al.  Deformability-based microfluidic cell pairing and fusion. , 2014, Lab on a chip.

[52]  Samuel Aparicio,et al.  High-throughput microfluidic single-cell RT-qPCR , 2011, Proceedings of the National Academy of Sciences.

[53]  Zhiyuan Hu,et al.  Device for whole genome sequencing single circulating tumor cells from whole blood. , 2019, Lab on a chip.

[54]  Aaron M. Streets,et al.  Microfluidic single-cell whole-transcriptome sequencing , 2014, Proceedings of the National Academy of Sciences.

[55]  Nicholas Pervolarakis,et al.  Tumour heterogeneity and metastasis at single-cell resolution , 2018, Nature Cell Biology.

[56]  T. Matsunaga,et al.  Gel-based cell manipulation method for isolation and genotyping of single-adherent cells. , 2019, The Analyst.

[57]  Lawrence D. True,et al.  Integrative Clinical Genomics of Advanced Prostate Cancer , 2015, Cell.

[58]  Y. Zu,et al.  High-Throughput Isolation of Cell Protrusions at Single-cell Precision for Profiling Subcellular Gene Expression. , 2019, Angewandte Chemie.

[59]  Huabing Yin,et al.  Raman-activated cell sorting based on dielectrophoretic single-cell trap and release. , 2015, Analytical chemistry.

[60]  Jin-Ming Lin,et al.  Single-cell assay on microfluidic devices. , 2019, The Analyst.

[61]  R. Sandberg,et al.  Full-Length mRNA-Seq from single cell levels of RNA and individual circulating tumor cells , 2012, Nature Biotechnology.

[62]  D. Weitz,et al.  Tracking lineages of single cells in lines using a microfluidic device , 2009, Proceedings of the National Academy of Sciences.

[63]  Dino Di Carlo,et al.  High-Throughput Assessment of Cellular Mechanical Properties. , 2015, Annual review of biomedical engineering.

[64]  Hongshen Ma,et al.  Technologies for label-free separation of circulating tumor cells: from historical foundations to recent developments. , 2014, Lab on a chip.

[65]  Chengzhi Hu,et al.  Characterization of size-dependent mechanical properties of tip-growing cells using a lab-on-chip device. , 2016, Lab on a chip.

[66]  Chang-Soo Lee,et al.  A programmable microfluidic static droplet array for droplet generation, transportation, fusion, storage, and retrieval. , 2015, Lab on a chip.

[67]  D R Walt,et al.  Application of high-density optical microwell arrays in a live-cell biosensing system. , 2000, Analytical biochemistry.

[68]  M. Toner,et al.  A highly-occupied, single-cell trapping microarray for determination of cell membrane permeability. , 2017, Lab on a chip.

[69]  Juan Xu,et al.  Pneumatic microfluidics-based multiplex single-cell array. , 2016, Biosensors & bioelectronics.

[70]  John P Wikswo,et al.  Microfluidic platform for real-time signaling analysis of multiple single T cells in parallel. , 2008, Lab on a chip.

[71]  Jin‐Ming Lin,et al.  Single-cell identification by microfluidic-based in situ extracting and online mass spectrometric analysis of phospholipids expression , 2019, Chemical science.

[72]  Soo Hyeon Kim,et al.  Highly efficient single cell arraying by integrating acoustophoretic cell pre-concentration and dielectrophoretic cell trapping. , 2015, Lab on a chip.

[73]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[74]  Veronica Sanchez-Freire,et al.  Microfluidic single-cell real-time PCR for comparative analysis of gene expression patterns , 2012, Nature Protocols.

[75]  Joonwon Kim,et al.  A microfluidic-based dynamic microarray system with single-layer pneumatic valves for immobilization and selective retrieval of single microbeads , 2014 .

[76]  Yuchao Li,et al.  Optical fan for single‐cell screening , 2019, Journal of biophotonics.

[77]  A. Carrel PURE CULTURES OF CELLS , 1912, The Journal of experimental medicine.

[78]  Luke P. Lee,et al.  Single-cell enzyme concentrations, kinetics, and inhibition analysis using high-density hydrodynamic cell isolation arrays. , 2006, Analytical chemistry.

[79]  Swee Jin Tan,et al.  Microdevice for the isolation and enumeration of cancer cells from blood , 2009, Biomedical microdevices.

[80]  Stephen R Quake,et al.  Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq. , 2016, Cell reports.

[81]  Jongyoon Han,et al.  Expansion of patient-derived circulating tumor cells from liquid biopsies using a CTC microfluidic culture device , 2017, Nature Protocols.

[82]  Subra Suresh,et al.  Kinetics of sickle cell biorheology and implications for painful vasoocclusive crisis , 2015, Proceedings of the National Academy of Sciences.

[83]  J. Lo,et al.  On-chip porous microgel generation for microfluidic enhanced VEGF detection. , 2015, Biosensors & bioelectronics.

[84]  Arye Nehorai,et al.  Optimization of microfluidic microsphere-trap arrays. , 2013, Biomicrofluidics.

[85]  Q. Lin,et al.  A Mechanically Tunable Microfluidic Cell-Trapping Device. , 2014, Sensors and actuators. A, Physical.

[86]  Dayu Liu,et al.  Screening Therapeutic Agents Specific to Breast Cancer Stem Cells Using a Microfluidic Single-Cell Clone-Forming Inhibition Assay. , 2020, Small.

[87]  J E Ferrell,et al.  The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. , 1998, Science.

[88]  M. Burns,et al.  Asymmetric traps array for particle transport , 2015 .

[89]  J. Auwerx,et al.  An automated microfluidic platform for C. elegans embryo arraying, phenotyping, and long-term live imaging , 2015, Scientific Reports.

[90]  Hongshen Ma,et al.  Cell separation based on size and deformability using microfluidic funnel ratchets. , 2012, Lab on a chip.

[91]  Hongshen Ma,et al.  Deterministic microfluidic ratchet based on the deformation of individual cells. , 2011, Physical review. E, Statistical, nonlinear, and soft matter physics.

[92]  Helene Andersson Svahn,et al.  Droplet microfluidics--a tool for single-cell analysis. , 2012, Angewandte Chemie.

[93]  Wenming Liu,et al.  Construction of single-cell arrays and assay of cell drug resistance in an integrated microfluidic platform. , 2016, Lab on a chip.

[94]  B. Karlan,et al.  A scalable filtration method for high throughput screening based on cell deformability. , 2019, Lab on a chip.

[95]  R. Jaenisch,et al.  Microfluidic Control of Cell Pairing and Fusion , 2009, Nature Methods.

[96]  Long Pang,et al.  Digital microfluidics for cell manipulation , 2019, TrAC Trends in Analytical Chemistry.

[97]  Chwee Teck Lim,et al.  Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients. , 2010, Biosensors & bioelectronics.

[98]  Jaehoon Chung,et al.  Traceable clonal culture and chemodrug assay of heterogeneous prostate carcinoma PC3 cells in microfluidic single cell array chips. , 2014, Biomicrofluidics.

[99]  L. Liang,et al.  Real-time detection and monitoring of the drug resistance of single myeloid leukemia cells by diffused total internal reflection. , 2018, Lab on a chip.

[100]  Chang-Soo Lee,et al.  Monitoring of chromosome dynamics of single yeast cells in a microfluidic platform with aperture cell traps. , 2016, Lab on a chip.

[101]  C. Hansen,et al.  High-throughput microfluidic single-cell digital polymerase chain reaction. , 2013, Analytical chemistry.

[102]  N. Neff,et al.  Reconstructing lineage hierarchies of the distal lung epithelium using single cell RNA-seq , 2014, Nature.

[103]  Marcel Ottens,et al.  Programmable v-type valve for cell and particle manipulation in microfluidic devices. , 2016, Lab on a chip.

[104]  Fengchao Wang,et al.  A high throughput platform for stem cell-niche co-cultures and downstream gene expression analysis , 2015, Nature Cell Biology.

[105]  R. Templer,et al.  A first step towards practical single cell proteomics: a microfluidic antibody capture chip with TIRF detection. , 2011, Lab on a chip.

[106]  Wan Abu Bakar Wan Abas,et al.  Benchtop Technologies for Circulating Tumor Cells Separation Based on Biophysical Properties , 2015, BioMed research international.

[107]  S. Fan,et al.  Single-Cell-Derived Tumor-Sphere Formation and Drug-Resistance Assay Using an Integrated Microfluidics. , 2019, Analytical chemistry.

[108]  Hongshen Ma,et al.  Microfluidic analysis of red blood cell deformability. , 2014, Journal of biomechanics.

[109]  Wong Cheng Lee,et al.  Multivariate biophysical markers predictive of mesenchymal stromal cell multipotency , 2014, Proceedings of the National Academy of Sciences.

[110]  Jin‐Ming Lin,et al.  Microfluidic Devices in the Fast-Growing Domain of Single-Cell Analysis. , 2018, Chemistry.

[111]  Kyung-A Hyun,et al.  Continuous enrichment of circulating tumor cells using a microfluidic lateral flow filtration chip. , 2015, Journal of chromatography. A.

[112]  T. Zhao,et al.  Microfluidic device embedding electrodes for dielectrophoretic manipulation of cells‐A review , 2018, Electrophoresis.

[113]  Sung-Hwan Kim,et al.  Microwell fabrication methods and applications for cellular studies , 2013 .

[114]  Mengsu Yang,et al.  On-site formation of emulsions by controlled air plugs. , 2014, Small.

[115]  A. Valero,et al.  Optimization of microfluidic single cell trapping for long-term on-chip culture. , 2010, Lab on a chip.

[116]  Kai Zhang,et al.  Hand-Held and Integrated Single-Cell Pipettes , 2014, Journal of the American Chemical Society.

[117]  P. H. Yap,et al.  An optofluidic imaging system to measure the biophysical signature of single waterborne bacteria. , 2014, Lab on a chip.

[118]  Hongshen Ma,et al.  Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability. , 2015, Lab on a chip.

[119]  A. Hamburger,et al.  Primary bioassay of human myeloma stem cells. , 1977, The Journal of clinical investigation.

[120]  M. Hertog,et al.  Digital microfluidic chip technology for water permeability measurements on single isolated plant protoplasts , 2014 .

[121]  Jin-Ming Lin,et al.  Dean flow assisted cell ordering system for lipid profiling in single-cells using mass spectrometry. , 2018, Chemical communications.

[122]  M. Saito,et al.  Centrifugal microfluidic platform for single-cell level cardiomyocyte-based drug profiling and screening. , 2015, Lab on a chip.

[123]  Allon M. Klein,et al.  Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells , 2015, Cell.

[124]  Changhuei Yang,et al.  A high-efficiency microfluidic device for size-selective trapping and sorting. , 2014, Lab on a chip.

[125]  Paul C. Blainey,et al.  A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages , 2016, Nature Communications.

[126]  E. Yoon,et al.  Scaling and automation of a high-throughput single-cell-derived tumor sphere assay chip. , 2016, Lab on a chip.

[127]  Hongshen Ma,et al.  Microfluidic micropipette aspiration for measuring the deformability of single cells. , 2012, Lab on a chip.

[128]  I. Weissman,et al.  Stem cells, cancer, and cancer stem cells , 2001, Nature.

[129]  Koji Sugioka,et al.  Ship-in-a-bottle femtosecond laser integration of optofluidic microlens arrays with center-pass units enabling coupling-free parallel cell counting with a 100% success rate. , 2015, Lab on a chip.