Persistent Luminescence Strontium Aluminate Nanoparticles as Reporters in Lateral Flow Assays

Demand for highly sensitive, robust diagnostics and environmental monitoring methods has led to extensive research in improving reporter technologies. Inorganic phosphorescent materials exhibiting persistent luminescence are commonly found in electroluminescent displays and glowing paints but are not widely used as reporters in diagnostic assays. Persistent luminescence nanoparticles (PLNPs) offer advantages over conventional photoluminescent probes, including the potential for enhanced sensitivity by collecting time-resolved measurements or images with decreased background autofluorescence while eliminating the need for expensive optical hardware, superior resistance to photobleaching, amenability to quantitation, and facile bioconjugation schemes. We isolated rare-earth doped strontium aluminate PLNPs from larger-particle commercial materials by wet milling and differential sedimentation and water-stabilized the particles by silica encapsulation using a modified Stöber process. Surface treatment with aldehyde silane followed by reductive amination with heterobifunctional amine-poly(ethylene glycol)-carboxyl allowed covalent attachment of proteins to the particles using standard carbodiimide chemistry. NeutrAvidin PLNPs were used in lateral flow assays (LFAs) with biotinylated lysozyme as a model analyte in buffer and monoclonal anti-lysozyme HyHEL-5 antibodies at the test line. Preliminary experiments revealed a limit of detection below 100 pg/mL using the NeutrAvidin PLNPs, which was approximately an order of magnitude more sensitive than colloidal gold.

[1]  Li Zhan-jun,et al.  A facile and effective method to prepare long-persistent phosphorescent nanospheres and its potential application for in vivo imaging , 2012 .

[2]  Weihong Tan,et al.  Surface modification of silica nanoparticles to reduce aggregation and nonspecific binding. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[3]  Yong Zhang,et al.  Small upconverting fluorescent nanoparticles for biomedical applications. , 2010, Small.

[4]  J. Lakowicz Principles of fluorescence spectroscopy , 1983 .

[5]  Gregory T. A. Kovacs,et al.  Optical Scanner for Immunoassays With Up-Converting Phosphorescent Labels , 2008, IEEE Transactions on Biomedical Engineering.

[6]  Thomas Maldiney,et al.  Effect of core diameter, surface coating, and PEG chain length on the biodistribution of persistent luminescence nanoparticles in mice. , 2011, ACS nano.

[7]  T. L. Mercier,et al.  Mechanism of Phosphorescence Appropriate for the Long-Lasting Phosphors Eu2+-Doped SrAl2O4 with Codopants Dy3+ and B3+ , 2005 .

[8]  Geertruida A. Posthuma-Trumpie,et al.  Lateral flow (immuno)assay: its strengths, weaknesses, opportunities and threats. A literature survey , 2009, Analytical and bioanalytical chemistry.

[9]  Wenyu Li,et al.  Encapsulation of strontium aluminate phosphors to enhance water resistance and luminescence , 2009 .

[10]  A. Rezania,et al.  Bioactivation of Metal Oxide Surfaces. 1. Surface Characterization and Cell Response , 1999 .

[11]  Guilan Wang,et al.  Novel fluorescent europium chelate-doped silica nanoparticles: preparation, characterization and time-resolved fluorometric application , 2004 .

[12]  Scott R. Manalis,et al.  Measuring the mass, density, and size of particles and cells using a suspended microchannel resonator , 2007 .

[13]  Seppo Ylä-Herttuala,et al.  In vitro targeting of avidin-expressing glioma cells with biotinylated persistent luminescence nanoparticles. , 2012, Bioconjugate chemistry.

[14]  Wieslaw Strek,et al.  Persistent luminescence phenomena in materials doped with rare earth ions , 2003 .

[15]  X. Chen,et al.  Encapsulating MAl2O4:Eu2+, Dy3+ (M = Sr, Ca, Ba) phosphors with triethanolamine to enhance water resistance , 2011 .

[16]  G. Han,et al.  Gel combustion synthesis and luminescence properties of nanoparticles of monoclinic SrAl2O4:Eu2+,Dy3+ , 2009 .

[17]  P. Holloway,et al.  Role of the surface in luminescent processes. , 2004, Chemical reviews.

[18]  Thierry Gacoin,et al.  Biological applications of rare-earth based nanoparticles. , 2011, ACS nano.

[19]  Didier Gourier,et al.  Controlling electron trap depth to enhance optical properties of persistent luminescence nanoparticles for in vivo imaging. , 2011, Journal of the American Chemical Society.

[20]  E. Diamandis,et al.  Europium chelate labels in time-resolved fluorescence immunoassays and DNA hybridization assays. , 1990, Analytical chemistry.

[21]  Yoshio Kobayashi,et al.  Direct coating of gold nanoparticles with silica by a seeded polymerization technique. , 2003, Journal of colloid and interface science.

[22]  S. Prabakar,et al.  Hydrolysis and condensation kinetics of two component organically modified silica sols , 1997 .

[23]  R. Willson,et al.  Association and dissociation kinetics of anti-hen egg lysozyme monoclonal antibodies HyHEL-5 and HyHEL-10. , 1998, Biophysical journal.

[24]  P. Venge,et al.  Lateral flow immunoassay using Europium (III) chelate microparticles and time-resolved fluorescence for eosinophils and neutrophils in whole blood. , 2007, Clinical chemistry.

[25]  G. V. Chester,et al.  Solid State Physics , 2000 .

[26]  D. Mao,et al.  Eu2+ activated long persistent strontium aluminate nano scaled phosphor prepared by precipitation method , 2006 .

[27]  M. Lastusaari,et al.  Electronic structure of the SrAl2O4:Eu2+ persistent luminescence material , 2009 .

[28]  Can T. Xu,et al.  Balancing power density based quantum yield characterization of upconverting nanoparticles for arbitrary excitation intensities. , 2013, Nanoscale.

[29]  John-Christopher Boyer,et al.  Absolute quantum yield measurements of colloidal NaYF4: Er3+, Yb3+ upconverting nanoparticles. , 2010, Nanoscale.

[30]  Huimin Liu,et al.  Phosphorescent dynamics in SrAl2O4: Eu2 +, Dy3 + single crystal fibers , 1998 .

[31]  C. Fyfe,et al.  Quantitative kinetic analysis by high-resolution 29Si NMR spectroscopy of the initial stages in the sol-gel formation of silica gel from tetraethoxysilane , 1995 .

[32]  Hajime Yamamoto,et al.  Mechanism of long phosphorescence of SrAl2O4:Eu2+, Dy3+ and CaAl2O4:Eu2+, Nd3+ , 1997 .

[33]  Helmut K. Schmidt,et al.  Principles of hydrolysis and condensation reaction of alkoxysilanes , 1984 .

[34]  Robert V. Brill,et al.  Applied Statistics and Probability for Engineers , 2004, Technometrics.

[35]  Jorma Hölsä,et al.  Persistent luminescence of Eu2+ doped alkaline earth aluminates, MAl2O4:Eu2+ , 2001 .

[36]  J. Burton,et al.  Detection of analytes by immunoassay using up-converting phosphor technology. , 2001, Analytical biochemistry.

[37]  Mats Nilsson,et al.  Lateral-flow and up-converting phosphor reporters to detect single-stranded nucleic acids in a sandwich-hybridization assay. , 2003, Analytical biochemistry.

[38]  Xuedong Song,et al.  Time-resolved luminescent lateral flow assay technology. , 2008, Analytica chimica acta.

[39]  Xingdong Lü Silica encapsulation study on SrAl2O4:Eu2+, Dy3+ phosphors , 2005 .

[40]  A. McCormick,et al.  Kinetic and thermodynamic study of the hydrolysis of silicon alkoxides in acidic alcohol solutions , 1993 .

[41]  S. Manalis,et al.  Weighing of biomolecules, single cells and single nanoparticles in fluid , 2007, Nature.

[42]  B. Mothudi,et al.  PL and CL degradation and characteristics of SrAl2O4: Eu2+,Dy3+ phosphors , 2012 .

[43]  G. Kovacs,et al.  Evolving point-of-care diagnostics using up-converting phosphor bioanalytical systems. , 2009, Analytical chemistry.

[44]  Tero Soukka,et al.  Performance of fluorescent europium(III) nanoparticles and colloidal gold reporters in lateral flow bioaffinity assay. , 2012, Analytical biochemistry.

[45]  N. A. Mufti,et al.  Upconverting phosphor reporters in immunochromatographic assays. , 2001, Analytical biochemistry.

[46]  H. Jiao,et al.  Search for new phosphors in Eu2+ doped MgAl2O4–SrAl2O4–BaAl2O4 ternary system by combinatorial approach , 2011 .

[47]  Aydogan Ozcan,et al.  Integrated rapid-diagnostic-test reader platform on a cellphone. , 2012, Lab on a chip.

[48]  Zhenkun Zhang,et al.  Synthesis of poly(ethylene glycol) (PEG)-grafted colloidal silica particles with improved stability in aqueous solvents. , 2007, Journal of colloid and interface science.

[49]  B. Geng,et al.  One-step synthesis and morphology evolution of luminescent Eu2+ doped strontium aluminate nanostructures , 2010 .

[50]  Aijun Zeng,et al.  A Simple Optical Reader for Upconverting Phosphor Particles Captured on Lateral Flow Strip , 2009, IEEE Sensors Journal.

[51]  Yong Zhang,et al.  Upconversion fluorescence imaging of cells and small animals using lanthanide doped nanocrystals. , 2008, Biomaterials.

[52]  H Tanke,et al.  Use of up-converting phosphor reporters in lateral-flow assays to detect specific nucleic acid sequences: a rapid, sensitive DNA test to identify human papillomavirus type 16 infection. , 2001, Clinical chemistry.

[53]  Nobuyoshi Takeuchi,et al.  A New Long Phosphorescent Phosphor with High Brightness, SrAl2 O 4 : Eu2 + , Dy3 + , 1996 .

[54]  Eric S. Nordman,et al.  A Low-Cost, High-Performance System for Fluorescence Lateral Flow Assays , 2013, Biosensors.

[55]  Martin Malmsten,et al.  Effect of chain density on inhibition of protein adsorption by poly(ethylene glycol) based coatings , 1998 .