Tunable pores for measuring concentrations of synthetic and biological nanoparticle dispersions.

Scanning ion occlusion sensing (SIOS), a technique that uses a tunable pore to detect the passage of individual nano-scale objects, is applied here for the rapid, accurate and direct measurement of synthetic and biological nanoparticle concentrations. SIOS is able to characterize smaller particles than other direct count techniques such as flow cytometry or Coulter counters, and the direct count avoids approximations such as those necessary for turbidity measurements. Measurements in a model system of 210-710 nm diameter polystyrene particles demonstrate that the event frequency scales linearly with applied pressure and concentration, and that measured concentrations are independent of particle type and size. Both an external-calibration and a calibration-free measurement method are demonstrated. SIOS is then applied to measure concentrations of Baculovirus occlusion bodies, with a diameter of ~1 μm, and the marine photosynthetic cyanobacterium Prochlorococcus, with a diameter of ~600 nm. The determined concentrations agree well with results from counting with microscopy (a 17% difference between the mean concentrations) and flow cytometry (6% difference between the mean concentrations), respectively.

[1]  G. Willmott,et al.  Reversible mechanical actuation of elastomeric nanopores , 2008, Nanotechnology.

[2]  L. Nielsen,et al.  Sensitivity of Helicoverpa armigera nucleopolyhedrovirus polyhedra to sodium dodecyl sulfate , 2003 .

[3]  L. Brannon-Peppas,et al.  Nanoparticle and targeted systems for cancer therapy. , 2004, Advanced drug delivery reviews.

[4]  Mauro Ferrari,et al.  Nanotechnology for breast cancer therapy , 2009, Biomedical microdevices.

[5]  Arezou A Ghazani,et al.  Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. , 2006, Nano letters.

[6]  Williamk . W. Li.  From cytometry to macroecology: a quarter century quest in microbial oceanography , 2009 .

[7]  G. Golomb,et al.  Alendronate-loaded nanoparticles deplete monocytes and attenuate restenosis. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[8]  Matt Trau,et al.  Advances in Resistive Pulse Sensors: Devices bridging the void between molecular and microscopic detection. , 2011, Nano today.

[9]  Lisa R. Moore,et al.  Utilization of different nitrogen sources by the marine cyanobacteria Prochlorococcus and Synechococcus , 2002 .

[10]  A. D. Young,et al.  An Introduction to Fluid Mechanics , 1968 .

[11]  Boguslaw Szewczyk,et al.  Baculoviruses-- re-emerging biopesticides. , 2006, Biotechnology advances.

[12]  P. Greenfield,et al.  In vitro production studies with a wild-type Helicoverpa baculovirus , 2004, Cytotechnology.

[13]  J. Maizel,et al.  The polypeptides of adenovirus. I. Evidence for multiple protein components in the virion and a comparison of types 2, 7A, and 12. , 1974, Virology.

[14]  Richard M Crooks,et al.  A carbon nanotube-based coulter nanoparticle counter. , 2004, Accounts of chemical research.

[15]  L. Park,et al.  Fabrication of charged particles for electrophoretic display , 2006 .

[16]  M. Barry,et al.  Current advances and future challenges in Adenoviral vector biology and targeting. , 2007, Current gene therapy.

[17]  Erkki Ruoslahti,et al.  A high-throughput label-free nanoparticle analyser. , 2011, Nature nanotechnology.

[18]  Valerie L. Ng,et al.  Practical Flow Cytometry, 4th Edition , 2004 .

[19]  G. B. Petersen,et al.  Dynamically resizable nanometre-scale apertures for molecular sensing , 2007 .

[20]  C. P. Bean,et al.  Electrokinetic measurements with submicron particles and pores by the resistive pulse technique , 1977 .

[21]  V. Altuzar,et al.  Atmospheric pollution profiles in Mexico City in two different seasons , 2003 .

[22]  Sallie W. Chisholm,et al.  A novel free-living prochlorophyte abundant in the oceanic euphotic zone , 1988, Nature.

[23]  I. Uhnoo,et al.  Direct identification of enteric adenovirus, a candidate new serotype, associated with infantile gastroenteritis , 1980, Journal of clinical microbiology.

[24]  C. P. Bean,et al.  Counting and Sizing of Submicron Particles by the Resistive Pulse Technique , 1970 .

[25]  James A. Fay,et al.  Introduction to Fluid Mechanics , 1994 .

[26]  Warren C W Chan,et al.  Nanoparticle-mediated cellular response is size-dependent. , 2008, Nature nanotechnology.

[27]  S. Fitzpatrick,et al.  Size distribution analysis of recombinant adenovirus using disc centrifugation , 1998, Journal of Industrial Microbiology and Biotechnology.

[28]  N. Ferry.  Editorial [Hot Topic: Liver Directed Gene Therapy: A Long Road to Clinical Applications (Guest Editor: Nicolas Ferry)] , 2009 .

[29]  H. Claustre,et al.  Prochlorococcus and Synechococcus: A comparative study of their optical properties in relation to their size and pigmentation , 1993 .

[30]  Chang Woo Kim,et al.  Encapsulated‐Dye All‐Organic Charged Colored Ink Nanoparticles for Electrophoretic Image Display , 2009, Advanced materials.

[31]  Helmuth van Es,et al.  Rapid determination of adenoviral vector titers by quantitative real-time PCR. , 2001, Journal of virological methods.

[32]  L. Barbu-Tudoran,et al.  Effects of different application parameters on penetration characteristics and arterial vessel wall integrity after local nanoparticle delivery using a porous balloon catheter. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[33]  Charles R. Martin,et al.  Resistive-Pulse SensingFrom Microbes to Molecules , 2000 .

[34]  Geoff R. Willmott,et al.  Quantitative sizing of nano/microparticles with a tunable elastomeric pore sensor. , 2011, Analytical chemistry.

[35]  Howard M. Shapiro,et al.  Practical Flow Cytometry , 1985 .

[36]  H. L. Weissberg.  End Correction for Slow Viscous Flow through Long Tubes , 1962 .

[37]  Maureen L. Coleman,et al.  Code and context: Prochlorococcus as a model for cross-scale biology. , 2007, Trends in microbiology.

[38]  M. Grinstaff,et al.  The performance of expansile nanoparticles in a murine model of peritoneal carcinomatosis. , 2011, Biomaterials.

[39]  Mauro Ferrari,et al.  Nanogeometry: beyond drug delivery. , 2008, Nature nanotechnology.

[40]  R W DeBlois,et al.  Sizes and concentrations of several type C oncornaviruses and bacteriophage T2 by the resistive-pulse technique , 1977, Journal of virology.

[41]  Lydia L. Sohn,et al.  Quantitative sensing of nanoscale colloids using a microchip Coulter counter , 2001 .

[42]  Russell J Mumper,et al.  Novel D-penicillamine carrying nanoparticles for metal chelation therapy in Alzheimer's and other CNS diseases. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[43]  Michelle Low,et al.  Investigative Study of Nucleic Acid-Gold Nanoparticle Interactions Using Laser-based Techniques, Electron Microscopy, and Resistive Pulse Sensing with a Nanopore , 2011 .

[44]  H. Ackermann,et al.  A morphological investigation of 23 baculoviruses , 1983 .

[45]  D. Vaulot,et al.  Prochlorococcus, a Marine Photosynthetic Prokaryote of Global Significance , 1999, Microbiology and Molecular Biology Reviews.

[46]  A. Nienhuis.  Development of gene therapy for blood disorders. , 2008, Blood.

[47]  M. Delano,et al.  Emerging implications of nanotechnology on cancer diagnostics and therapeutics , 2006, Cancer.

[48]  M. Trau,et al.  Tunable nano/micropores for particle detection and discrimination: scanning ion occlusion spectroscopy. , 2010, Small.

[49]  D. Tritton,et al.  Physical Fluid Dynamics , 1977 .

[50]  Sha Jin,et al.  Nanoparticle‐Mediated Drug Delivery and Gene Therapy , 2007, Biotechnology progress.