Real-time modulated nanoparticle separation with an ultra-large dynamic range.

Nanoparticles exhibit size-dependent properties which make size-selective purification of proteins, DNA or synthetic nanoparticles essential for bio-analytics, clinical medicine, nano-plasmonics and nano-material sciences. Current purification methods of centrifugation, column chromatography and continuous-flow techniques suffer from particle aggregation, multi-stage process, complex setups and necessary nanofabrication. These increase process costs and time, reduce efficiency and limit dynamic range. Here, we achieve an unprecedented real-time nanoparticle separation (51-1500 nm) using a large-pore (2 μm) deterministic lateral displacement (DLD) device. No external force fields or nanofabrication are required. Instead, we investigated innate long-range electrostatic influences on nanoparticles within a fluid medium at different NaCl ionic concentrations. In this study we account for the electrostatic forces beyond Debye length and showed that they cannot be assumed as negligible especially for precise nanoparticle separation methods such as DLD. Our findings have enabled us to develop a model to simultaneously quantify and modulate the electrostatic force interactions between nanoparticle and micropore. By simply controlling buffer solutions, we achieve dynamic nanoparticle size separation on a single device with a rapid response time (<20 s) and an enlarged dynamic range (>1200%), outperforming standard benchtop centrifuge systems. This novel method and model combines device simplicity, isolation precision and dynamic flexibility, opening opportunities for high-throughput applications in nano-separation for industrial and biological applications.

[1]  H. Butt,et al.  Measuring electrostatic, van der Waals, and hydration forces in electrolyte solutions with an atomic force microscope. , 1991, Biophysical journal.

[2]  J. Sturm,et al.  Ratchets in hydrodynamic flow: more than waterwheels , 2014, Interface Focus.

[3]  Yan Zeng,et al.  Effect of particle size and Debye length on order parameters of colloidal silica suspensions under confinement , 2011 .

[4]  A. Minor,et al.  Size-dependent mechanical properties of Mg nanoparticles used for hydrogen storage , 2015 .

[5]  Thomas Laurell,et al.  Continuous separation of cells and particles in microfluidic systems. , 2010, Chemical Society reviews.

[6]  Shashi Ranjan,et al.  DLD pillar shape design for efficient separation of spherical and non-spherical bioparticles. , 2014, Lab on a chip.

[7]  Nicole Pamme,et al.  Continuous flow separations in microfluidic devices. , 2007, Lab on a chip.

[8]  Subra Suresh,et al.  Size‐Dependent Endocytosis of Nanoparticles , 2009, Advanced materials.

[9]  J. Geist,et al.  Separation and metrology of nanoparticles by nanofluidic size exclusion. , 2010, Lab on a chip.

[10]  A. L. Stevens,et al.  A patterned anisotropic nanofluidic sieving structure for continuous-flow separation of DNA and proteins. , 2007, Nature nanotechnology.

[11]  D. Anselmetti,et al.  Continuous-flow separation of nanoparticles by electrostatic sieving at a micro-nanofluidic interface. , 2011, Journal of separation science.

[12]  Jaehun Chun,et al.  Length Fractionation of Carbon Nanotubes Using Centrifugation , 2008 .

[13]  Peter Jönsson,et al.  Tipping the balance of deterministic lateral displacement devices using dielectrophoresis. , 2009, Lab on a chip.

[14]  Thomas Laurell,et al.  Seed particle-enabled acoustic trapping of bacteria and nanoparticles in continuous flow systems. , 2012, Lab on a chip.

[15]  J. Sturm,et al.  Continuous Particle Separation Through Deterministic Lateral Displacement , 2004, Science.

[16]  Joseph D'Silva,et al.  Deterministic separation of cancer cells from blood at 10 mL/min. , 2012, AIP advances.

[17]  Vahid Sandoghdar,et al.  Geometry-induced electrostatic trapping of nanometric objects in a fluid , 2010, Nature.

[18]  T. Laue,et al.  Modern applications of analytical ultracentrifugation. , 1999, Annual review of biophysics and biomolecular structure.

[19]  C. S. Sipaut,et al.  Size-dependent physicochemical and optical properties of silica nanoparticles , 2009 .

[20]  E. Kumacheva,et al.  Properties and emerging applications of self-assembled structures made from inorganic nanoparticles. , 2010, Nature nanotechnology.

[21]  Vincent M. Rotello,et al.  Applications of Nanoparticles in Biology , 2008 .

[22]  H Bridle,et al.  Deterministic lateral displacement for particle separation: a review. , 2014, Lab on a chip.

[23]  W J Stark,et al.  Industrial applications of nanoparticles. , 2015, Chemical Society reviews.

[24]  Tuncay Alan,et al.  Particle separation using virtual deterministic lateral displacement (vDLD). , 2014, Lab on a chip.

[25]  R. Cerione,et al.  Microfluidic isolation of cancer-cell-derived microvesicles from hetergeneous extracellular shed vesicle populations , 2014, Biomedical Microdevices.

[26]  J. Sturm,et al.  Deterministic hydrodynamics: Taking blood apart , 2006, Proceedings of the National Academy of Sciences.

[27]  David W Inglis,et al.  Crossing microfluidic streamlines to lyse, label and wash cells. , 2008, Lab on a chip.

[28]  Shashi Ranjan,et al.  Rotational separation of non-spherical bioparticles using I-shaped pillar arrays in a microfluidic device , 2013, Nature Communications.

[29]  J. J. López-García,et al.  Poisson-Boltzmann description of the electrical double layer including ion size effects. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[30]  H. Flyvbjerg,et al.  Concentrating genomic length DNA in a microfabricated array. , 2015, Physical review letters.

[31]  John A. Davis,et al.  Microfluidic Separation of Blood Components through Deterministic Lateral Displacement , 2008 .

[32]  István Lagzi,et al.  Nanoseparations: Strategies for size and/or shape-selective purification of nanoparticles , 2011 .

[33]  B. Cabane,et al.  How to concentrate nanoparticles and avoid aggregation? , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[34]  Carsten Sönnichsen,et al.  Separation of nanoparticles by gel electrophoresis according to size and shape. , 2007, Nano letters.

[35]  O. Salata,et al.  Applications of nanoparticles in biology and medicine , 2004, Journal of nanobiotechnology.

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

[37]  L Mahadevan,et al.  Density-gradient-free microfluidic centrifugation for analytical and preparative separation of nanoparticles. , 2014, Nano letters.

[38]  Andrew Z. Wang,et al.  Nanoparticles and their applications in cell and molecular biology. , 2014, Integrative biology : quantitative biosciences from nano to macro.

[39]  M. J. Kim,et al.  Chemically modified solid state nanopores for high throughput nanoparticle separation , 2010, Journal of physics. Condensed matter : an Institute of Physics journal.