Nanofluidics for sub-single cellular studies: Nascent progress, critical technologies, and future perspectives

ABSTRACT In the field of cell studies, there is a burgeoning trend to further downscale the investigation from a single-cell level to a sub-single-cell level. Subcellular matter is the basic content in cells and correlates with cell heterogeneity. Sub-single cellular studies focus on the subcellular matter in single cells and aim to understand the details and heterogeneity of individual cells in terms of the subcellular matter or even at the single component/vesicle/molecule level. Hence, sub-single cellular studies can provide deeper insights into fundamental cell biology and the development of new diagnostic and therapeutic technologies and applications. Nonetheless, the contents of a single cell are not only ultra-small in volume but also extremely complex in composition, far exceeding the capabilities of most tools used in current cell studies. We believe that nanofluidics holds great potential in providing ideal tools for sub-single cellular studies, not only because of their capability to handle femtoliter/attoliter-scale samples, but also because of their possibility to manipulate and analyze subcellular matters at the single component/vesicle/molecule level in a high-throughput manner. In this review, we summarize the efforts in the field of nanofluidics for sub-single cellular studies, focusing on nascent progress and critical technologies that have the potential to overcome the technical bottlenecks. Some challenges and future opportunities to integrate with information sciences are also discussed.

[1]  S. Cabrini,et al.  A nanochannel through a plasmonic antenna gap: an integrated device for single particle counting. , 2019, Lab on a chip.

[2]  K. Mawatari,et al.  Micro/extended-nano sampling interface from a living single cell. , 2017, The Analyst.

[3]  Yan Xu,et al.  An Integrated Glass Nanofluidic Device Enabling In-situ Electrokinetic Probing of Water Confined in a Single Nanochannel under Pressure-Driven Flow Conditions. , 2015, Small.

[4]  Takehiko Kitamori,et al.  NMR study of water molecules confined in extended nanospaces. , 2007, Angewandte Chemie.

[5]  F. Westerlund,et al.  Optical DNA mapping in nanofluidic devices: principles and applications. , 2017, Lab on a chip.

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

[7]  Hongkai Wu,et al.  Recent Developments in Microfluidics for Cell Studies , 2014, Advanced materials.

[8]  S. Jacobson,et al.  Ion transport in nanofluidic funnels. , 2010, ACS nano.

[9]  P. Giusto,et al.  Nanofluidic Ion Transport and Energy Conversion through Ultrathin Free-Standing Polymeric Carbon Nitride Membranes. , 2018, Angewandte Chemie.

[10]  Nanofluidics is on the rise , 2020, Nature Materials.

[11]  Koji Yamaguchi,et al.  Regeneration of glass nanofluidic chips through a multiple-step sequential thermochemical decomposition process at high temperatures. , 2015, Lab on a chip.

[12]  Takehiko Kitamori,et al.  Bonding of glass nanofluidic chips at room temperature by a one-step surface activation using an O2/CF4 plasma treatment. , 2013, Lab on a chip.

[13]  Z. Siwy,et al.  Nanofluidic diode. , 2007, Nano letters.

[14]  Lei Jiang,et al.  Nanofluidics in two-dimensional layered materials: inspirations from nature. , 2017, Chemical Society reviews.

[15]  Lei Jiang,et al.  Ion Transport in Nanofluidic Devices for Energy Harvesting , 2019, Joule.

[16]  Makusu Tsutsui,et al.  Controlling DNA translocation through gate modulation of nanopore wall surface charges. , 2011, ACS nano.

[17]  A. Herr,et al.  Subcellular western blotting of single cells , 2017, Microsystems & Nanoengineering.

[18]  Yifang Chen,et al.  Applications of nanoimprint lithography/hot embossing: a review , 2015 .

[19]  Takehiko Kitamori,et al.  Extended-nanofluidics: fundamental technologies, unique liquid properties, and application in chemical and bio analysis methods and devices. , 2014, Analytical chemistry.

[20]  J. Eijkel,et al.  Nanofluidic technology for biomolecule applications: a critical review. , 2010, Lab on a chip.

[21]  P. Reddy,et al.  Anti-Aging Strategies Based on Cellular Reprogramming. , 2016, Trends in molecular medicine.

[22]  K. Mawatari,et al.  Communication—Evaporation Driven Micro/Nanofluidic Pumping Device , 2018 .

[23]  P. Reimann,et al.  Hydrodynamic slip on DNA observed by optical tweezers-controlled translocation experiments with solid-state and lipid-coated nanopores. , 2014, Nano letters.

[24]  J. Eijkel,et al.  Principles and applications of nanofluidic transport. , 2009, Nature nanotechnology.

[25]  K. Mawatari,et al.  Nano X-ray diffractometry device for nanofluidics. , 2018, Lab on a Chip.

[26]  Lydéric Bocquet,et al.  Nanofluidics coming of age , 2020, Nature Materials.

[27]  K. Mawatari,et al.  Lipid Bilayer-Modified Nanofluidic Channels of Sizes with Hundreds of Nanometers for Characterization of Confined Water and Molecular/Ion Transport. , 2020, The journal of physical chemistry letters.

[28]  R. Markus,et al.  Rapid and accurate analysis of stem cell-derived extracellular vesicles with super resolution microscopy and live imaging , 2018, Biochimica et biophysica acta. Molecular cell research.

[29]  A. Theberge,et al.  Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology. , 2010, Angewandte Chemie.

[30]  Yan Xu.  Nanofluidics: A New Arena for Materials Science , 2018, Advanced materials.

[31]  Bo Yu,et al.  Nanochannel electroporation delivers precise amounts of biomolecules into living cells. , 2011, Nature nanotechnology.

[32]  Klaus Pantel,et al.  Biology, detection, and clinical implications of circulating tumor cells , 2014, EMBO molecular medicine.

[33]  J. Eijkel,et al.  Technologies for nanofluidic systems: top-down vs. bottom-up--a review. , 2005, Lab on a chip.

[34]  Sung Jae Kim,et al.  Nanofluidic concentration devices for biomolecules utilizing ion concentration polarization: theory, fabrication, and applications. , 2010, Chemical Society reviews.

[35]  Patrick Tabeling,et al.  Physics and technological aspects of nanofluidics. , 2014, Lab on a chip.

[36]  Albert Folch,et al.  Microvalves and Micropumps for BioMEMS , 2011, Micromachines.

[37]  S. Prakash,et al.  A three-state nanofluidic field effect switch. , 2015, Nano letters.

[38]  Amy E. Reece,et al.  Microfluidic techniques for high throughput single cell analysis. , 2016, Current opinion in biotechnology.

[39]  F. Persson,et al.  Probing physical properties of a DNA-protein complex using nanofluidic channels. , 2014, Small.

[40]  Carol Korzeniewski,et al.  From nanochannel-induced proton conduction enhancement to a nanochannel-based fuel cell. , 2005, Nano letters.

[41]  John E. Chandler,et al.  Label-free imaging of the native, living cellular nanoarchitecture using partial-wave spectroscopic microscopy , 2016, Proceedings of the National Academy of Sciences.

[42]  K. Mawatari,et al.  Nonfluorescent Molecule Detection in 102 nm Nanofluidic Channels by Photothermal Optical Diffraction. , 2019, Analytical chemistry.

[43]  A. Kiyatkin,et al.  Multistrip Western blotting: a tool for comparative quantitative analysis of multiple proteins. , 2015, Methods in molecular biology.

[44]  D. Baker,et al.  Cellular senescence in renal ageing and disease , 2017, Nature Reviews Nephrology.

[45]  S. Kryuchkov,et al.  Revealing the Surface Effect on Gas Transport and Mechanical Properties in Nonporous Polymeric Membranes in Terms of Surface Free Energy. , 2020, Langmuir : the ACS journal of surfaces and colloids.

[46]  A. Matheu,et al.  Towards precision medicine: linking genetic and cellular heterogeneity in gastric cancer , 2018, Therapeutic advances in medical oncology.

[47]  K. Mawatari,et al.  Femtoliter droplet handling in nanofluidic channels: a Laplace nanovalve. , 2012, Analytical chemistry.

[48]  Garry P Nolan,et al.  High‐throughput precision measurement of subcellular localization in single cells , 2017, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[49]  Priscille Laub,et al.  Nanofluidics Drives Point-of-care Technology for on the Spot Protein Marker Analysis with Rapid Actionable Results , 2019, Journal of Nanomedicine & Nanotechnology.

[50]  K. Leong,et al.  Nonendocytic Delivery of Lipoplex Nanoparticles into Living Cells Using Nanochannel Electroporation , 2014, Advanced healthcare materials.

[51]  Zeng-Qiang Wu,et al.  High-performance bioanalysis based on ion concentration polarization of micro-/nanofluidic devices , 2019, Analytical and Bioanalytical Chemistry.

[52]  P. Doll,et al.  Fabrication of silicon nanopillar arrays by electron beam lithography and reactive ion etching for advanced bacterial adhesion studies , 2019, Materials Research Express.

[53]  Miko Elwenspoek,et al.  Capillary filling speed of water in nanochannels , 2004 .

[54]  P. Giusto,et al.  Nanofluidic Ion Transport and Energy Conversion through Ultrathin Free-Standing Polymeric Carbon Nitride Membranes. , 2018, Angewandte Chemie.

[55]  Z. Siwy,et al.  Rectification of Ion Current in Nanopores Depends on the Type of Monovalent Cations: Experiments and Modeling , 2014, The journal of physical chemistry. C, Nanomaterials and interfaces.

[56]  K. Mir,et al.  Lipid-Based Passivation in Nanofluidics , 2012, Nano letters.

[57]  J. Shapter,et al.  Microbial cell lysis and nucleic acid extraction via nanofluidic channel , 2015 .

[58]  Hong Chen,et al.  A novel fluidic control method for nanofluidics by solvent-solvent interaction in a hybrid chip. , 2015, Lab on a chip.

[59]  Takehiko Kitamori,et al.  Low-temperature direct bonding of glass nanofluidic chips using a two-step plasma surface activation process , 2011, Analytical and Bioanalytical Chemistry.

[60]  C. Kohnhorst,et al.  Subcellular functions of proteins under fluorescence single-cell microscopy. , 2016, Biochimica et biophysica acta.

[61]  Clara Granzotto,et al.  Development and application of an ELISA method for the analysis of protein-based binding media of artworks , 2015 .

[62]  J Michael Ramsey,et al.  Fabrication of sub-5 nm nanochannels in insulating substrates using focused ion beam milling. , 2011, Nano letters.

[63]  H. Park,et al.  Ion transport in graphene nanofluidic channels. , 2016, Nanoscale.

[64]  Matthew C Traub,et al.  Advances in Nanoimprint Lithography. , 2016, Annual review of chemical and biomolecular engineering.

[65]  Takehiko Kitamori,et al.  Microchip-based cellular biochemical systems for practical applications and fundamental research: from microfluidics to nanofluidics , 2011, Analytical and Bioanalytical Chemistry.

[66]  Fan Zhang,et al.  Single Nanochannel Platform for Detecting Chiral Drugs. , 2017, Analytical chemistry.

[67]  S. Kandlikar,et al.  Review of fabrication of nanochannels for single phase liquid flow , 2006 .

[68]  S. Jacobson,et al.  Monitoring Assembly of Virus Capsids with Nanofluidic Devices. , 2015, ACS nano.

[69]  G. Banker,et al.  The cellular mechanisms that maintain neuronal polarity , 2016, Nature Reviews Neuroscience.

[70]  Nobuhiro Matsumoto,et al.  Site-specific nanopatterning of functional metallic and molecular arbitrary features in nanofluidic channels. , 2015, Lab on a chip.

[71]  Nader Pourmand,et al.  Nanopipettes as Monitoring Probes for the Single Living Cell: State of the Art and Future Directions in Molecular Biology , 2018, Cells.

[72]  A. Haghiri-Gosnet,et al.  Pressure-assisted selective preconcentration in a straight nanochannel. , 2013, Analytical chemistry.

[73]  Peter J Burke,et al.  Nanofluidic platform for single mitochondria analysis using fluorescence microscopy. , 2013, Analytical chemistry.

[74]  J. Han,et al.  Creating sub-50 nm nanofluidic junctions in a PDMS microchip via self-assembly process of colloidal silica beads for electrokinetic concentration of biomolecules. , 2014, Lab on a chip.

[75]  Takatoki Yamamoto,et al.  Single-Molecule Detection of DNA in a Nanochannel by High-Field Strength-Assisted Electrical Impedance Spectroscopy , 2019, Micromachines.

[76]  D. Beebe,et al.  The present and future role of microfluidics in biomedical research , 2014, Nature.

[77]  Shuo Kang,et al.  Integrated biodetection in a nanofluidic device. , 2014, ACS nano.

[78]  Geo Semini,et al.  Chemical Mapping of Leishmania Infection in Live Cells by SERS Microscopy. , 2018, Analytical chemistry.

[79]  J. Sweedler,et al.  Nanofluidics in chemical analysis. , 2010, Chemical Society reviews.

[80]  K. Mawatari,et al.  A single-molecule ELISA device utilizing nanofluidics. , 2018, In Analysis.

[81]  Shashi K Murthy,et al.  Microfluidic Sample Preparation for Single Cell Analysis. , 2016, Analytical chemistry.

[82]  Katrin Wondraczek,et al.  Fast, Label-Free Tracking of Single Viruses and Weakly Scattering Nanoparticles in a Nanofluidic Optical Fiber. , 2015, ACS nano.

[83]  Anders Kristensen,et al.  Nanofluidic devices towards single DNA molecule sequence mapping , 2012, Journal of biophotonics.

[84]  Quanliang Cao,et al.  Rotational motion and lateral migration of an elliptical magnetic particle in a microchannel under a uniform magnetic field , 2017 .

[85]  Fredrik Westerlund,et al.  A nano flow cytometer for single lipid vesicle analysis. , 2017, Lab on a chip.

[86]  K. Ando,et al.  Nanofluidic Biosensor Created by Bonding Patterned Model Cell Membrane and Silicone Elastomer with Silica Nanoparticles. , 2018, Small.

[87]  K. Mawatari,et al.  Femtoliter nanofluidic valve utilizing glass deformation. , 2019, Lab on a chip.

[88]  Jin Zhai,et al.  Light and pH Cooperative Nanofluidic Diode Using a Spiropyran‐Functionalized Single Nanochannel , 2012, Advanced materials.

[89]  Yuejun Kang,et al.  A simple technique of constructing nano-roughened polydimethylsiloxane surface to enhance mesenchymal stem cell adhesion and proliferation , 2017 .

[90]  K. Mawatari,et al.  Nano-bubble Valve , 2021, Microfluidics and Nanofluidics.

[91]  D. Issadore,et al.  Combining Machine Learning and Nanofluidic Technology To Diagnose Pancreatic Cancer Using Exosomes. , 2017, ACS nano.

[92]  Takehiko Kitamori,et al.  Nanochannels on a Fused-Silica Microchip and Liquid Properties Investigation by Time-Resolved Fluorescence Measurements , 2002 .

[93]  K. Mawatari,et al.  Detachable glass micro/nanofluidic device. , 2019, Biomicrofluidics.

[94]  K. Ando,et al.  Nanometric Gap Structure with a Fluid Lipid Bilayer for the Selective Transport and Detection of Biological Molecules. , 2016, Langmuir : the ACS journal of surfaces and colloids.

[95]  Atsushi Harada,et al.  Soft Matter‐Regulated Active Nanovalves Locally Self‐Assembled in Femtoliter Nanofluidic Channels , 2016, Advanced materials.

[96]  Xueye Chen,et al.  Review in manufacturing methods of nanochannels of bio-nanofluidic chips , 2018 .

[97]  Stephen C. Jacobson,et al.  Fundamental Studies of Nanofluidics: Nanopores, Nanochannels, and Nanopipets , 2014, Analytical chemistry.

[98]  S. Kelley.  Advancing Ultrasensitive Molecular and Cellular Analysis Methods to Speed and Simplify the Diagnosis of Disease. , 2017, Accounts of chemical research.

[99]  S. Jacobson,et al.  AC Electroosmotic Pumping in Nanofluidic Funnels. , 2016, Analytical chemistry.

[100]  Y. Xu,et al.  Fabrication of Ultranarrow Nanochannels with Ultrasmall Nanocomponents in Glass Substrates , 2021, Micromachines.

[101]  Matthew B Stone,et al.  Super-Resolution Microscopy: Shedding Light on the Cellular Plasma Membrane. , 2017, Chemical reviews.

[102]  K. Mawatari,et al.  Femtoliter Volumetric Pipette and Flask Utilizing Nanofluidics. , 2020, The Analyst.

[103]  Shana O Kelley,et al.  Beyond the Capture of Circulating Tumor Cells: Next-Generation Devices and Materials. , 2016, Angewandte Chemie.

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

[105]  M. Matsubara,et al.  ペロブスカイトマンガン酸塩Gd0.55Sr0.45MnO3における超高速光誘導絶縁体‐強磁性体転移 , 2007 .

[106]  Kuan Chen,et al.  Electron beam lithography in nanoscale fabrication: recent development , 2003 .

[107]  Chih-Yang Wang,et al.  Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells , 2015, Nature.

[108]  Nobuhiro Matsumoto,et al.  Flexible and in situ fabrication of nanochannels with high aspect ratios and nanopillar arrays in fused silica substrates utilizing focused ion beam , 2015 .

[109]  Rafael Yuste,et al.  Targeted intracellular voltage recordings from dendritic spines using quantum-dot-coated nanopipettes. , 2017, Nature nanotechnology.