Profiling Cell-Matrix Adhesion Using Digitalized Acoustic Streaming.

Profiling the kinetics of cell-matrix adhesion is of great importance to understand many physiological and pathological processes such as morphogenesis, tissue homeostasis, wound healing, and tumorigenesis. Here, we developed a novel digital acoustofluidic device for parallel profiling cell-matrix adhesion at the single-cell level. By introducing a localized and uniform acoustic streaming into an open chamber microfluidic device, the adherent cells within the open chamber can be detached by the streaming-induced Stokes drag force. By digitally regulating pulsed acoustic power from a low level to high levels, the hundreds of adherent cells can be ruptured from the fibronectin-coated substrate accordingly, and their adhesive forces (from several pN to several nN) and kinetics can be determined by the applied power and cell incubation time. As a proof-of-concept application for studying cancer metastasis, we applied this technique to measure the adhesion strength and kinetics of human breast cancer cells to extracellular matrix such as fibronectin and compared their metastatic potentials by measuring rupture force of cancer cells representing malignant (MCF-7 cells and MDA-MB-231 cells) and non-malignant (MCF-10A cells) states. Our acoustofluidic device is simple, easy for operation, and capable of parallelly measure hundreds of individual cells' adhesion forces with a resolution at the pN level. Thus, we expect this device could be widely used for both fundamental cell biology research as well as the development of cancer diagnostics and tissue engineering technologies.

[1]  Zhuhao Wu,et al.  A Digital Acoustofluidic Pump Powered by Localized Fluid-Substrate Interactions. , 2019, Analytical chemistry.

[2]  Zheng Ao,et al.  A digital acoustofluidic device for on-demand and oil-free droplet generation , 2018, Nanotechnology.

[3]  Peng Li,et al.  Acoustic tweezers for the life sciences , 2018, Nature Methods.

[4]  Maria Bondesson,et al.  Acoustic assembly of cell spheroids in disposable capillaries , 2018, Nanotechnology.

[5]  S. Hao,et al.  Nucleus of Circulating Tumor Cell Determines Its Translocation Through Biomimetic Microconstrictions and Its Physical Enrichment by Microfiltration. , 2018, Small.

[6]  E. Peterman,et al.  Single-Cell Acoustic Force Spectroscopy: Resolving Kinetics and Strength of T Cell Adhesion to Fibronectin. , 2018, Cell reports.

[7]  Po-Hsun Huang,et al.  Digital acoustofluidics enables contactless and programmable liquid handling , 2018, Nature Communications.

[8]  Gong Cheng,et al.  A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells. , 2018, Small.

[9]  Abraham P. Lee,et al.  Whole-blood sorting, enrichment and in situ immunolabeling of cellular subsets using acoustic microstreaming , 2018, Microsystems & Nanoengineering.

[10]  Jin Ho Jung,et al.  A Pumpless Acoustofluidic Platform for Size-Selective Concentration and Separation of Microparticles. , 2017, Analytical chemistry.

[11]  H. Bruus,et al.  Ultrasound Characterization of Microbead and Cell Suspensions by Speed of Sound Measurements of Neutrally Buoyant Samples. , 2017, Analytical chemistry.

[12]  Hyoung Won Baac,et al.  Selective Photomechanical Detachment and Retrieval of Divided Sister Cells from Enclosed Microfluidics for Downstream Analyses. , 2017, ACS nano.

[13]  Shana O Kelley,et al.  Profiling Functional and Biochemical Phenotypes of Circulating Tumor Cells Using a Two-Dimensional Sorting Device. , 2017, Angewandte Chemie.

[14]  Po-Hsun Huang,et al.  Surface Acoustic Waves Grant Superior Spatial Control of Cells Embedded in Hydrogel Fibers , 2016, Advanced materials.

[15]  Nicholas Mavrogiannis,et al.  Microfluidics made easy: A robust low-cost constant pressure flow controller for engineers and cell biologists. , 2016, Biomicrofluidics.

[16]  David J. Collins,et al.  Highly Localized Acoustic Streaming and Size-Selective Submicrometer Particle Concentration Using High Frequency Microscale Focused Acoustic Fields. , 2016, Analytical chemistry.

[17]  Subra Suresh,et al.  Three-dimensional manipulation of single cells using surface acoustic waves , 2016, Proceedings of the National Academy of Sciences.

[18]  J. Massagué,et al.  Metastatic colonization by circulating tumour cells , 2016, Nature.

[19]  Amelia Ahmad Khalili,et al.  A Review of Cell Adhesion Studies for Biomedical and Biological Applications , 2015, International journal of molecular sciences.

[20]  Brenna Hogan,et al.  Characterizing cell adhesion by using micropipette aspiration. , 2015, Biophysical journal.

[21]  Baoquan Ding,et al.  Tunable Rigidity of (Polymeric Core)–(Lipid Shell) Nanoparticles for Regulated Cellular Uptake , 2015, Advanced materials.

[22]  Peng Li,et al.  Controlling cell–cell interactions using surface acoustic waves , 2014, Proceedings of the National Academy of Sciences.

[23]  Liang Cao,et al.  Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications. , 2014, Pharmacology & therapeutics.

[24]  Ho Cheung Shum,et al.  Syringe-pump-induced fluctuation in all-aqueous microfluidic system implications for flow rate accuracy. , 2014, Lab on a chip.

[25]  Ye Ai,et al.  Separation of Escherichia coli Bacteria from Peripheral Blood Mononuclear Cells Using Standing Surface Acoustic Waves , 2013, Analytical chemistry.

[26]  Peng Li,et al.  Surface acoustic wave microfluidics. , 2013, Lab on a chip.

[27]  P. Decuzzi,et al.  Modulating the vascular behavior of metastatic breast cancer cells by curcumin treatment , 2012, Front. Oncol..

[28]  Masayuki Yamato,et al.  Shear stress-dependent cell detachment from temperature-responsive cell culture surfaces in a microfluidic device. , 2012, Biomaterials.

[29]  D. Cheresh,et al.  Tumor angiogenesis: molecular pathways and therapeutic targets , 2011, Nature Medicine.

[30]  Thomas Laurell,et al.  Forthcoming Lab on a Chip tutorial series on acoustofluidics: acoustofluidics-exploiting ultrasonic standing wave forces and acoustic streaming in microfluidic systems for cell and particle manipulation. , 2011, Lab on a chip.

[31]  Nam-Trung Nguyen,et al.  High-throughput micromixers based on acoustic streaming induced by surface acoustic wave , 2011 .

[32]  D A Weitz,et al.  Surface acoustic wave actuated cell sorting (SAWACS). , 2010, Lab on a chip.

[33]  Kristyn S Masters,et al.  Measurement of single-cell adhesion strength using a microfluidic assay , 2010, Biomedical microdevices.

[34]  David Boettiger,et al.  Mechanically Activated Integrin Switch Controls α5β1 Function , 2009, Science.

[35]  B. Garmy-Susini,et al.  Integrins in angiogenesis and lymphangiogenesis , 2008, Nature Reviews Cancer.

[36]  Stephen J. Haswell,et al.  Attachment and detachment of living cells on modified microchannel surfaces in a microfluidic-based lab-on-a-chip system , 2008 .

[37]  C. Simmons,et al.  Matrix-dependent adhesion of vascular and valvular endothelial cells in microfluidic channels. , 2007, Lab on a chip.

[38]  Siyang Zheng,et al.  Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells. , 2007, Journal of chromatography. A.

[39]  Hidenori Suzuki,et al.  The SPR signal in living cells reflects changes other than the area of adhesion and the formation of cell constructions. , 2007, Biosensors & bioelectronics.

[40]  Douglas A Lauffenburger,et al.  Microfluidic shear devices for quantitative analysis of cell adhesion. , 2004, Analytical chemistry.

[41]  A. Sonnenberg,et al.  Erratum: Integrins in regulation of tissue development and function. J Pathol; 200: 471–480 , 2003 .

[42]  Catherine D Reyes,et al.  A centrifugation cell adhesion assay for high-throughput screening of biomaterial surfaces. , 2003, Journal of biomedical materials research. Part A.

[43]  Milan Mrksich,et al.  A surface chemistry approach to studying cell adhesion , 2000 .

[44]  Hermann E. Gaub,et al.  Discrete interactions in cell adhesion measured by single-molecule force spectroscopy , 2000, Nature Cell Biology.

[45]  Donald E. Ingber,et al.  The structural and mechanical complexity of cell-growth control , 1999, Nature Cell Biology.