Label-Enhanced Surface Plasmon Resonance: A New Concept for Improved Performance in Optical Biosensor Analysis

Surface plasmon resonance (SPR) is a well-established optical biosensor technology with many proven applications in the study of molecular interactions as well as in surface and material science. SPR is usually applied in the label-free mode which may be advantageous in cases where the presence of a label may potentially interfere with the studied interactions per se. However, the fundamental challenges of label-free SPR in terms of limited sensitivity and specificity are well known. Here we present a new concept called label-enhanced SPR, which is based on utilizing strongly absorbing dye molecules in combination with the evaluation of the full shape of the SPR curve, whereby the sensitivity as well as the specificity of SPR is significantly improved. The performance of the new label-enhanced SPR method was demonstrated by two simple model assays: a small molecule assay and a DNA hybridization assay. The small molecule assay was used to demonstrate the sensitivity enhancement of the method, and how competitive assays can be used for relative affinity determination. The DNA assay was used to demonstrate the selectivity of the assay, and the capabilities in eliminating noise from bulk liquid composition variations.

[1]  B. Liedberg,et al.  Principles of biosensing with an extended coupling matrix and surface plasmon resonance , 1993 .

[2]  Bo Johnsson,et al.  A novel hydrogel matrix on gold surfaces in surface plasmon resonance sensors for fast and efficient covalent immobilization of ligands , 1990 .

[3]  Joshua LaBaer,et al.  Emerging tools for real‐time label‐free detection of interactions on functional protein microarrays , 2005, The FEBS journal.

[4]  Rebecca L Rich,et al.  Why you should be using more SPR biosensor technology. , 2004, Drug discovery today. Technologies.

[5]  Yuze Sun,et al.  Sensitive optical biosensors for unlabeled targets: a review. , 2008, Analytica chimica acta.

[6]  SPR sensor signal amplification based on dye-doped polymer particles , 2006 .

[7]  J. Hofkens,et al.  Comprar Handbook of Fluorescence Spectroscopy and Imaging: From Ensemble to Single Molecules | Markus Sauer | 9783527316694 | Wiley , 2007 .

[8]  S. Kubitschko,et al.  Sensitivity enhancement of optical immunosensors with nanoparticles. , 1997, Analytical biochemistry.

[9]  Jiří Homola,et al.  Electromagnetic Theory of Surface Plasmons , 2006 .

[10]  D G Myszka,et al.  Advances in surface plasmon resonance biosensor analysis. , 2000, Current opinion in biotechnology.

[11]  Walter Huber,et al.  Biomolecular interaction analysis in drug discovery using surface plasmon resonance technology. , 2006, Current pharmaceutical design.

[12]  H A Macleod,et al.  Surface plasmon resonance spectroscopy as a tool for investigating the biochemical and biophysical properties of membrane protein systems. I: Theoretical principles. , 1997, Biochimica et biophysica acta.

[13]  R. Karlsson,et al.  Real-time competitive kinetic analysis of interactions between low-molecular-weight ligands in solution and surface-immobilized receptors. , 1994, Analytical biochemistry.

[14]  H Roos,et al.  Biosensor analysis of the interaction between immobilized human serum albumin and drug compounds for prediction of human serum albumin binding levels. , 2000, Journal of medicinal chemistry.

[15]  Wolfgang Knoll,et al.  Evanescent field in surface plasmon resonance and surface plasmon field-enhanced fluorescence spectroscopies. , 2004, Analytical chemistry.

[16]  Rebecca L. Rich,et al.  Grading the commercial optical biosensor literature—Class of 2008: ‘The Mighty Binders’ , 2009, Journal of molecular recognition : JMR.

[17]  Anthony M Giannetti,et al.  From experimental design to validated hits a comprehensive walk-through of fragment lead identification using surface plasmon resonance. , 2011, Methods in enzymology.

[18]  R. H. Pantell,et al.  Surface plasmon resonance and immunosensors , 1984 .

[19]  D. Astruc,et al.  Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. , 2004, Chemical reviews.

[20]  L. Mahan,et al.  Correction to “The Kinetics of Competitive Radioligand Binding Predicted by the Law of Mass Action” , 2014, Molecular Pharmacology.

[21]  Massimo Guardigli,et al.  Markus Sauer, Johan Hofkens, and Jörg Enderlein: Handbook of fluorescence spectroscopy and imaging: from ensemble to single molecules , 2012, Analytical and Bioanalytical Chemistry.

[22]  Mark E. Cooper,et al.  Label-free biosensors : techniques and applications , 2009 .

[23]  R. Masel Principles of Adsorption and Reaction on Solid Surfaces , 1996 .

[24]  I. Korhonen,et al.  Characterization of thin films and their structures in surface plasmon resonance measurements , 1995 .

[25]  Rebecca L Rich,et al.  Higher-throughput, label-free, real-time molecular interaction analysis. , 2007, Analytical biochemistry.

[26]  A. Kolomenskiǐ,et al.  Surface-plasmon resonance spectrometry and characterization of absorbing liquids. , 2000, Applied optics.

[27]  Agustín González-Cano,et al.  Absorption as a selective mechanism in surface plasmon resonance fiber optic sensors. , 2006, Optics letters.

[28]  R. Schasfoort,et al.  Handbook of surface plasmon resonance , 2008 .

[29]  Zohra Ben Lakhdar,et al.  Absorption and related optical dispersion effects on the spectral response of a surface plasmon resonance sensor. , 2008, Applied optics.

[30]  Lorenz M. Mayr,et al.  Label-Free Technologies for Drug Discovery , 2011 .

[31]  Björn Persson,et al.  Attomolar sensitivity in bioassays based on surface plasmon fluorescence spectroscopy. , 2004, Journal of the American Chemical Society.

[32]  J. Delrow,et al.  Enhanced sensitivity of wavelength modulated surface plasmon resonance devices using dispersion from a dye solution , 1999 .

[33]  J. Homola Present and future of surface plasmon resonance biosensors , 2003, Analytical and bioanalytical chemistry.

[34]  B. Liedberg,et al.  Surface plasmon resonance for gas detection and biosensing , 1983 .

[35]  J. Homola Surface plasmon resonance sensors for detection of chemical and biological species. , 2008, Chemical reviews.

[36]  W. M. Albers,et al.  Surface Plasmon Resonance on Nanoscale Organic Films , 2011 .

[37]  R. Karlsson,et al.  Experimental design for kinetic analysis of protein-protein interactions with surface plasmon resonance biosensors. , 1997, Journal of immunological methods.

[38]  J. Homola,et al.  Surface plasmon resonance (SPR) sensors: approaching their limits? , 2009, Optics express.

[39]  Magnus Björsne,et al.  Label-Free Primary Screening and Affinity Ranking of Fragment Libraries Using Parallel Analysis of Protein Panels , 2008, Journal of biomolecular screening.

[40]  Fredrik Edfeldt,et al.  Affinity-based, biophysical methods to detect and analyze ligand binding to recombinant proteins: matching high information content with high throughput. , 2010, Journal of structural biology.

[41]  Yasunobu Sato,et al.  Flow-stress-induced discrimination of a K-ras point mutation by sandwiched polymer microsphere-enhanced surface plasmon resonance , 2004, Journal of biomaterials science. Polymer edition.