46

Surface Plasmon Resonance

K. Scott Phillips and Quan Jason Cheng

1. Introduction
SPR is an elegant surface sensitive optical technique most commonly employed for biointeraction analysis on a flat substrate. Although the concept was suggested as early as 1968 (1,2), the use of SPR for biosensing in its present capacity started to gain momentum from the mid-1980s (3). The most important advantage of SPR is its label-free nature. As explained below, SPR measures changes in the amount of material within about 200 nm of the surface. Because detection is based on refractive index, rather than a reporter molecule such as a fluorophore, there is no need to label the material that will be detected. The downside of this advantage is lack of specificity. Anything that binds or sticks to the surface will be detected, so one must be careful to eliminate this type of interference through careful experimental design, sophisticated surface chemistry, and often the use of a reference channel for comparison. Another advantage of SPR is that it is conducted in real time. Unlike endpoint measurements of binding or surface changes using bulk techniques such as fluorescence, the surface sensitivity of SPR, when used with a properly designed flow cell, allows monitoring of a surface interaction as it occurs. This real-time information can be fit to theoretical models to yield kinetic and thermodynamic parameters. The result is accurate determination of binding constants without waiting for equilibrium to be established, greatly facilitating analysis of large compound libraries. When combined with multiplex instruments, this is especially useful for pharmaceutical screening. SPR is also complementary to other nonlabeled surface sensitive analysis technologies such as QCM or impedance. Assuming complete monolayer coverage, thickness changes as little as several angstroms can be detected. Finally, because SPR is a spectroscopic technique, SPR imaging is also possible. In the applications section, we will discuss the exciting nature of SPR imaging spectroscopy (SPRi). For comprehensive reviews of SPR and SPR imaging, the reader is referred to references (417).

From: Molecular Biomethods Handbook, 2nd Edition. Edited by: J. M. Walker and R. Rapley Humana Press, Totowa, NJ

809

810

K. S. Phillips and Q. Cheng

2. How SPR Works

2.1. Instrumentation A variety of SPR instrumentation is available, ranging from inexpensive (<$10,000 US) to extremely high-end (>$300,000). A review of some instruments was recently published in the Analytical Chemistry A-pages (18). Since then, even more units have become available with powerful new features. Fig. 46.1 shows an SPR instrument setup with the common Kretschmann (1) configuration. The essential parts include a light source, a prism on a rotating stage, and a detector. The substrate sits on top of the prism, usually joined by a thin film of index matching fluid. Substrates are usually glass slides with a refractive index matching the prism. On top of the glass is a 50 nm layer of gold, sometimes with a thin chromium adhesion layer. The light source (typically a laser) is directed through a series of focusing and polarizing lenses into the prism at an angle normal to the bottom of the gold surface. Snells law describes the critical angle at which total internal reflection (TIR) occurs. In TIR mode, although no light comes out of the top of the prism at the reflecting gold surface, the photon electrical field extends 1/4 wavelength beyond it. The decaying em field is evanescent because it decays exponentially and is only useful within about 200 nm of the gold surface. Beyond that, the effects are too small to be experimentally useful in most cases. Near this surface, the light field can interact with a highly delocalized state of weakly bound electrons in gold. When the wavevectors of the incoming light and electron field match, they can resonantly couple. The prism is used to alter the momentum of light to make it ideal for this resonance condition. When the angle of incoming light allows for plasmon resonance, energy is lost, and the amount of reflected light is reduced. This produces a dip shaped curve on an angle vs. reflectivity plot. It is important to understand how this all relates to biointeraction analysis and detection of mass changes on the surface. Basically, an increase in mass near the surface, such as a bound ligand or thin film, changes the refractive index environment near the surface. Because the resonance condition depends on the refractive index near the surface, the minimum angle at which resonance occurs is highly sensitive to small changes.

Fig. 46.1. Kretschmann configuration of an SPR setup

Chapter 46 Surface Plasmon Resonance

811

2.2. Measurement Modes SPR measurement is usually performed in one of two ways. In the first, the angle can be scanned while the intensity of reflected light is monitored. As the stage rotates through the minimum angle, this produces a dip-shaped curve like that shown in Fig. 46.2. Although suitable for characterization purposes or static measurements, this route is normally too slow for monitoring changes over time. Some instruments include a software routine that can scan through a narrow range of angles around the minimum angle. Because this is much faster, it can be repeated continuously, and the software can adjust the range of angles scanned if the minimum angle changes, such as during a binding event. In this way, a plot of minimum angle versus time can be obtained. The other popular method of measurement is slightly more complex. First a reflectivity plot is obtained by rotating the stage through the minimum angle. Notice in Fig. 46.2 that the left and right sides of the dip shaped curve have a very steep slope. If the minimum angle condition was to change because of binding, the intensity would rapidly move up or down depending on that slope. In this way, the stage is set before starting an experiment and does not need to be scanned. As shown in Fig. 46.3, the change in intensity is plotted vs. time, and it increases (or decreases, depending on which slope is chosen) as binding occurs. A major advantage of this route is speed because data can be collected as fast as the detector can integrate it. The downside is that the data are less useful for theoretical calculations of thickness and must stay within a more narrow linear range. This method is popular for ligand-binding studies and others requiring high sensitivity and fast response.

1.0

0.8

Reflectivity (a.u.)

0.6

0.06

0.4
Reflectivity (a.u.)

0.05

0.2

()min

0.04

0.0
63.4 63.6 63.8 64.0 64.2 Minimum angle (degrees) 64.4 64.6

40

50

60 70 Minimum angle (degrees)

80

Fig. 46.2. Theoretical reflectivity as a function of minimum angle for a 1 nm (black dashed) and 2 nm (gray) organic film on a gold substrate. The difference in minimum angle can clearly be seen upon zooming in on the dip-shaped curve area (inset)

812

K. S. Phillips and Q. Cheng

Fig. 46.3. SPR plots of binding versus time for several concentrations of cholera toxin to receptor GM1 in supported membranes on silicate modified gold substrates. From ref. 72

2.3. Data Analysis 2.3.1. Thickness Evaluation For thickness determinations, quantitative analysis is performed by comparing the experimental data with theoretically predicted values of an optical multilayer stack. Several free programs are available on the web (Corn Group: http://corninfo.ps.uci.edu/calculations.html, Knoll Group: http://www.mpipmainz.mpg.de/knoll/soft/index.html) that will calculate thickness. An estimate must be made regarding appropriate input values for the optical parameters of all layers and thickness of individual layers, as well as the substrate thickness and refractive index and the wavelength of light used. To exactly determine the thickness of multiple layers without exact inputs for thickness and refractive index, multiple spectra can be analyzed at different wavelengths or in different media, solving for unknowns in a parallel fashion. 2.3.2. Kinetic Analysis Kinetic analysis has been made more routine with the aid of software packages specifically designed to work with certain instruments and flow cells. Typically, these set up model differential equations using a background subtracted response-time curve with inputs of analyte concentration, valency of the interaction, and a number of parameters related to mass transfer. A typical equation would involve species X binding to an immobilized species Y to form a complex XY. With a knowledge of surface density and solution concentration of species X and Y, the binding constants for association and dissociation can be solved. d[XY]/dt = ka [X][Y] kd[XY] (1)

Chapter 46 Surface Plasmon Resonance

813

The equations are solved numerically and plotted with the original curve to show the closeness of fit. More elaborate models can be used to reduce error resulting from mass transport limitations and better model intermediate binding steps and multivalent binding. Even more accurate values can be obtained by using global fitting of sensorgrams at several different concentrations.

3. Applications of SPR
Although the number of publications reporting the use of SPR started out in the dozens, over 2000 were published in 2006 alone. Many investigations using SPR for characterization of biomolecular interactions have extremely high citation rates because with SPR the authors were able to obtain data that was not previously accessible, thereby gaining new understanding of important and previously investigated biological systems. SPR is so versatile because it can be used for many interactions on a flat surface. Generally, larger molecules such as proteins are better for analysis because they have a larger mass and cause greater minimum angle change. However, highly sensitive instruments are pushing the detection limits lower so that SPR can be used with small compounds. Below we group the types of interactions into two main classes, nucleic acids and proteins, although many others have been achieved, such as lipids (19), saccharides (20) and gangliosides (21). 3.1. Nucleic Acids SPR has been used for DNA interactions with many different classes of compounds. Starting with small building blocks, it has been used for sequencing (22) and single nucleotide polymorphism analysis (23). SPR imaging has been demonstrated for DNA hybridization (24), DNA/RNA hybridization (25), and DNA/protein interactions (26). DNA/PNA and RNA/PNA interaction have also been investigated (27). DNA interaction with peptide subunits of a larger protein has been monitored to evaluate recognition (28). Chemically induced hairpin formation has been examined in DNA monolayers (29). 3.2. Proteins Some of the first reports of kinetic analysis were using antibody-antigen interactions (30). However, SPR is so sensitive to nonspecific adsorption that it has been used to screen for nonspecific protein adsorption to help improve biosensor methods (31). The carboxymethyldextran surface developed for gold surface modification was a key selling point of Biacore sensor chip technology and allowed for high immobilization efficiency with reduced hydrophobic nonspecific binding (32). The development of several different commercially available surfaces has also aided in opening up SPR analysis to different areas of biomolecular interaction study. One of the major uses remains the investigation and optimization of antibody antigen interactions (3337). These are key to many aspects of biology and biochemistry, and are one of the most well-investigated protein interaction systems. Another important area is the interaction of receptors with other proteins and smaller molecules (3846). It is important to understand how receptors function because they are responsible for many aspects of cell life. Because many membrane-bound receptors rely

814

K. S. Phillips and Q. Cheng

on changes in conformation and networks of noncovalent interactions, the nonlabeled advantage of SPR is a valuable tool in mechanism elucidation. The planar surface of an SPR substrate is also highly ideal for reconstituation of membrane receptors in supported lipid membranes that mimick the real cell membrane. Investigation of multiple protein complexes is also more facile with SPR because of the elimination of interference from fluorophores that are bulky and cause steric hindrance. The major histocompatibility (MHC) and T-cell receptor (TCR) complexes have been frequently studied (4754). Another area of interest is the investigation of vast and complex protein signaling networks (5559). Protein kinases are implicated in many disorders and new drugs that target phosphorylation or dephosphorylation by these enzymes are being investigated and found to be very potent with less side-effects. Proteinprotein interactions are too numerous, but a few high-impact examples are given as a starting point in the references (6065). SPR imaging has also been used for protein/protein interaction analysis (see the Following) and even proteinaptamer interactions (66).

4. Recent Advances and Future of SPR

4.1. SPR Imaging An important area of development is SPR imaging (SPRi), which has similar sensitivity to SPR spectroscopy but allows for spatially resolved measurements. A number of groups have demonstrated working systems (6772, to name a few) and at least three companies claim to offer SPR imaging instruments. The resolution of the method is limited compared with microscopy, typically to about 50m, but that is usually enough for quantitative analysis of suitably large arrays on a slide. The use of SPRi for pharmaceutical and genomic/proteomic screening holds out incredible promise for high-throughput analysis without the use and drawbacks of fluorescent labels, reducing costs. This combined with the real-time non-equilibrium analysis might help reduce the time of analysis anywhere that large libraries of compounds are being screened. 4.2. Hyphenated Techniques Hyphenated techniques are also becoming popular. Many instruments already offer several analysis options in conjunction with SPR. It is often combined with electrochemistry because the gold substrate can be used as a working electrode. It has also been combined with QCM, IR, and even downstream mass spectrometry. An interesting and exciting new technique combines SPR with fluorescence (SPFS) to create a labeled but surface sensitive detection method with ultra-high detection sensitivity (73). 4.3. Materials and Chemistry As SPR becomes a popular and common technique, many groups are investigating improved surface chemistry for the substrates (74). In general, many binding kinetics experiments are done in pure buffer with only one species of interest present. Thus, linkage chemistry is essential to optimize the accuracy and efficiency of binding constant determinations. The same chemistry that

Chapter 46 Surface Plasmon Resonance

815

has been used in other methods has also proved useful for SPR. For example, His-NTA linkage used in chromatographic methods (75) was found to increase the signal obtained for binding when compared with direct antibody linkages that have higher steric hindrance. The Corn group has also shown the importance of advanced surface chemistry in SPR imaging and gone to great efforts to develop a host of reliable methods using lithography (76) or microfluidic patterning (77) to pattern surfaces with reactive and nonreactive areas. An interesting recent trend is the use of thin silicate layers (10 nm) to cover the gold substrate and make the surface more like glass, for which a wide variety of well developed surface chemistry is available (7881). When analyzing real samples for clinical or environmental applications, surface chemistry often becomes the limiting factor for accurate and sensitive detection. These solutions have large numbers and concentrations of interfering molecules. Methods that work for fluorescence or other analysis techniques may not be suitable for SPR because any non-specific adsorption on the surface causes an increased signal. A major focus for biosensors proposed for clinical and environmental uses has been the reduction of NS adsorption through better surface chemistry such as biocompatible polymers (82). A new report shows how supported bilayer membranes can be used to cloak the surface, followed by removal of the cloak after binding, and measurement of specific signal (83). 4.4. Labels and Amplification One of the major developments for increasing sensitivity was the use of labeled SPR reagents. Gold nanoparticles labels were found to increase the signal response by >10-fold when compared with unlabeled samples (84). Although this strategy does allow for ultrasensitive detection with SPR, it is no longer a label-free method when used in this capacity. Gold nanoparticles may significantly interfere with binding of smaller molecules and the effects on binding constant determination should be carefully considered. For biosensing, however, they provide a means to increase both sensitivity and selectivity through the use of antibody-labeled nanoparticles. Another exciting new concept is the use of enzymes to provide amplification in SPR imaging of DNA arrays. Two strategies have been developed, one based on the RNase H enzyme (85) and another based on ligase T4 (86). The direct detection limit for DNA hybridization is about 1nM, but now genomic samples in the femtomolar range can be achieved. With these techniques added to the repertoire, detection of single-nucleotide polymorphisms also becomes feasible. SPRi looks to be highly competitive with fluorescence-based DNA arrays for high-throughput genomic screening.

5. Conclusions
It should be evident from this brief chapter that SPR has become an indispensable technique for scientific investigation of biomolecular interactions. Although it has some limitations, such as a lower sensitivity than fluorescence, the advantages of being label-free and real-time present a complementary alternative. Moreover, as SPR evolves, researchers are coming up with creative new ways to make it more sensitive, user-friendly, higher-throughput, and versatile

816

K. S. Phillips and Q. Cheng

for a wide range of investigation topics. A brief survey of the literature above showed that SPR has been applied to crucial high-impact projects in many of the key areas of biology and medicine being investigated today, and that the number of publications using SPR is increasing rapidly. We believe that as the cost of instruments becomes more affordable, it will enjoy widespread use. Further commercialization could make it an indispensable lab instrument just like optical plate readers or fluorescence scanners. The simple and elegant underlying principle of SPR lends to facile modification, such as hyphenated instruments, new materials for substrates, and improved surface chemistry.

References
1. Kretschm E, Raether H (1968) Radiative decay of non radiative surface plasmons excited by light. Zeitschrift Fur Naturforschung Part a-Astrophysik Physik Und Physikalische Chemie A 23:2135213 2. Otto A (1968) Excitation of nonradiative surface plasma waves in silver by method of frustrated total reflection. Zeitschrift Fur Physik 216:398& 3. Liedberg B, Nylander C, Lundstrom I (1983) Surface-plasmon resonance for gasdetection and biosensing. Sensors and Actuators 4:299304 4. Homola J (2003) Present and future of surface plasmon resonance biosensors. Anal Bioanal Chem 377:528539 5. Calander N (2006) Molecular detection and analysis by using surface plasmon resonances. Current Anal Chem 2:203211 6. Nedelkov D, Nelson RW (2006) Surface plasmon resonance mass spectrometry for protein analysis. Meth Mol Bio 328:131139 7. Rich RL, Myszka DG (2005) Survey of the year 2004 commercial optical biosensor literature. J Mol Recognition 18:431478 8. Homola J, Myszka D, Sinclair S (2002) Surface plasmon biosensors. In: Optical biosensors: present and future: Amsterdam: Newyork: Elsevier, 207, 251 9. McDonnell JM (2001) Surface plasmon resonance: towards an understanding of the mechanisms of biological molecular recognition. Current Opinion Chem Biol 5:572577 10. Rich RL, Myszka DG (2000) Advances in surface plasmon resonance biosensor analysis. Current Opin Biotechnol 11:5461 11. Karlsson R, Michaelsson A, Mattsson L (1991) Kinetic-analysis of monoclonal antibody-antigen interactions with a new biosensor based analytical system. J Immunol Methods 145:229240 12. Phillips KS, Cheng O (2007) Recent advances in surface plasmon resonance based techniques for bioanalysis. Anal Bioanal Chem 387:18311840 13. Steiner G (2004) Surface plasmon resonance imaging. Anal Bioanal Chem 379:328331 14. Cooper MA (2003) Label-free screening of bio- molecular interactions. Anal Bioanal Chem 377:834842 15. Ince R, Narayanaswamy R (2006) Analysis of the performance of interferometry, surface plasmon resonance and luminescence as biosensors and chemosensors. Analytica Chimica Acta 569:120 16. Katsamba PS, Navratilova I, Calderon-Cacia M, Fan L, Thornton K, Zhu MD, Vanden Bos T, Forte C, Friend D, Laird-Offringa I, Tavares G, Whatley J, Shi EG, Widom A, Lindquist KC, Klakamp S, Drake A, Bohmann D, Roell M, Rose L, Dorocke J, Roth B, Luginbuhl B, Myszka DG (2006) Kinetic analysis of a high-affinity antibody/antigen interaction performed by multiple Biacore users. Anal Biochem 352:208221 17. Besenicar M, Macek P, Lakey JH, Anderluh G (2006) Surface plasmon resonance in protein-membrane interactions. Chem Physics Lipids 141:169178 18. Mukhyopadyay R (2005) Anal Chem: 313A317A

Chapter 46 Surface Plasmon Resonance 19. Salim K, Bottomley MJ, Querfurth E, Zvelebil MJ, Gout I, Scaife R, Margolis RL, Gigg R, Smith CIE, Driscoll PC, Waterfield MD, and Panayotou G (1996) Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Brutons tyrosine kinase Embo J 15(22):62416250 20. Mach H, Volkin DB, Burke CJ, Middaugh CR, Linhardt RJ, Fromm JR, Loganathan D, Mattsson L (1993) Nature of the Interaction of Heparin with Acidic Fibroblast Growth-Factor. Biochemistry 32:54805489 21. Kuziemko GM, Stroh M, Stevens RC (1996) Cholera toxin binding affinity and specificity for gangliosides determined by surface plasmon resonance. Biochemistry 35:63756384 22. Natsume T, Nakayama H, Jansson O, Isobe T, Takio K, Mikoshiba K (2000) Combination of biomolecular interaction analysis and mass spectrometric amino acid sequencing, Anal Chem 72:41934198 23. Caruso F, Jory MJ, Bradberry GW, Sambles JR, Furlong DN (1998) Acousto-optic surface-plasmon resonance measurements of thin films on gold. J App Physics 83:10231028 24. Jordan CE, Frutos AG, Thiel AJ, Corn RM (1997) Surface plasmon resonance imaging measurements of DNA hybridization adsorption and streptavidin/DNA multilayer formation at chemically modified gold surfaces. Anal Chem 69:49394947 25. Nelson BP, Grimsrud TE, Liles MR, Goodman RM, Corn RM (2001) Surface plasmon resonance imaging measurements of DNA and RNA hybridization adsorption onto DNA microarrays. Anal Chem 73:17 26. Wegner GJ, Lee HJ, Marriott G, Corn RM (2003) Fabrication of histidine-tagged fusion protein arrays for surface plasmon resonance imaging studies of proteinprotein and protein-DNA interactions. Anal Chem 75:47404746 27. Jensen KK, Orum H, Nielsen PE, Norden B (1997) Kinetics for hybridization of peptide nucleic acids (PNA) with DNA and RNA studied with the BIAcore technique. Biochemistry 36:50725077 28. Wegner GJ, Lee HJ, Corn RM (2002) Characterization and optimization of peptide arrays for the study of epitope-antibody interactions using surface plasmon resonance imaging. Anal Chem 74:51615168 29. Smith EA, Kyo M, Kumasawa H, Nakatani K, Saito I, Corn RM (2002) Chemically induced hairpin formation in DNA monolayers. J Am Chem Soc 124:68106811 30. Karlsson R, Michaelsson A, Mattsson L (1991) Kinetic-analysis of monoclonal antibody-antigen interactions with a new biosensor based analytical system. J Immunol Meth 145:229240 31. Ostuni E, Chapman RG, Holmlin RE et al (2001) A survey of structureproperty relationships of surfaces that resist the adsorption of protein. Langmuir 17(18):56055620 32. Johnsson B, Lofas S, Lindquist G (1991) Immobilization of proteins to a carboxymethyldextran-modified gold surface for biospecific interaction analysis in surface-plasmon resonance sensors. Anal Biochem 198:268277 33. Holliger P, Prospero T, Winter G (1993) Diabodies small bivalent and bispecific antibody fragments. Proc Nat Acad Sci U S A 90:64446448 34. Griffiths AD, Malmqvist M, Marks JD, Bye JM, Embleton MJ, McCafferty J, Baier M, Holliger KP, Gorick BD, Hughesjones NC, Hoogenboom HR, Winter G (1993) Human anti-self antibodies with high specificity from phage display libraries. Embo J 12:725734 35. Marks JD, Griffiths AD, Malmqvist M, Clackson TP, Bye JM, Winter G (1992): Bypassing immunization building high-affinity human-antibodies by chain shuffling. Bio-Technology 10:779783 36. Wikstrand CJ, Hale LP, Batra SK, Hill ML, Humphrey PA, Kurpad SN, McLendon RE, Moscatello D, Pegram CN, Reist CJ, Traweek ST, Wong AJ, Zalutsky MR, Bigner DD (1995) Monoclonal antibodies against EGFRvlll are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res. 55:31403148

817

818

K. S. Phillips and Q. Cheng 37. Schier R, McCall A, Adams CP, Marshall KW, Merritt H, Yim M, Crawford RS, Weiner LM, Marks C, Marks JD (1996) Isolation of picomolar affinity Antic-erbB-2 single-chain Fv by molecular evolution of the complementarity determining regions in the center of the antibody binding site. J Mol Biol 263:551567 38. Pevsner J, Hsu SC, Braun JEA, Calakos N, Ting AE, Bennett MK, Scheller RH (1994): Specificity and regulation of a synaptic vesicle docking complex. Neuron 13:353361 39. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273:1436314367 40. Calakos N, Bennett MK, Peterson KE, Scheller RH (1994) Protein-protein interactions contributing to the specificity of intracellular vesicular trafficking. Science 263:11461149 41 Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (1998) Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci 18:128137 42. Alam SM, Travers PJ, Wung JL, Nasholds W, Redpath S, Jameson SC, Gascoigne NRJ (1996) T-cell-receptor affinity and thymocyte positive selection. Nature 381:616620 43. Greenlund AC, Morales MO, Viviano BL, Yan H, Krolewski J, Schreiber RD (1995) Stat recruitment by tyrosine-phosphorylated cytokine receptors an ordered reversible affinity-driven process. Immunity 2:677687 44. Schuster SC, Swanson RV, Alex LA, Bourret RB, Simon MI (1993) Assembly and function of a quaternary signal-transduction complex monitored by surfaceplasmon resonance. Nature 365:343347 45. Donaldson DD, Whitters MJ, Fitz IJ, Neben TY, Finnerty H, Henderson SL, OHara RM, Beier DR, Turner KJ, Wood CR, Collins M (1998) The murine IL-13 receptor alpha 2: molecular cloning, characterization, and comparison with marine IL-13 receptor. J Immunol 161:23172324 46. Nishikawa J, Saito K, Goto J, Dakeyama F, Matsuo M, Nishihara T (1999) New screening methods for chemicals with hormonal activities using interaction of nuclear hormone receptor with coactivator. Toxicol Appl Pharmacol 154:7683 47. Lyons DS, Lieberman SA, Hampl J, Boniface JJ, Chien YH, Berg LJ, Davis MM (1996) A TCR binds to antagonist ligands with lower affinities and faster dissociation rates than to agonists. Immunity 5:5361 48. Corr M, Slanetz AE, Boyd LF, Jelonek MT, Khilko S, Alramadi BK, Kim YS, Maher SE, Bothwell ALM, Margulies DH (1994) T-Cell receptor-Mhc class-I peptide interactions - affinity, kinetics, and specificity. Science 265:946949 49. Matsui K, Boniface JJ, Steffner P, Reay PA, Davis MM (1994) Kinetics of T-cell receptor-binding to peptide I-E(K) complexes correlation of the dissociation rate with T-cell responsiveness. Proc Natl Acad Sci USA 91:1286212866 50. Brown MH, Boles K, van der Merwe PA, Kumar V, Mathew PA, Barclay AN (1998) 2B4, the natural killer and T cell immunoglobulin super-family surface protein, is a ligand for CD48. J Exp Med 188:20832090 51. vanderMerwe PA, Bodian DL, Daenke S, Linsley P, Davis SJ (1997) CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics. J Exp Med 185:393403 52. Corr M, Boyd IF, Frankel SR, Kozlowski S, Padlan EA, Margulies DH (1992) Endogenous peptides of a soluble major histocompatibility complex class-I molecule, H-2I(D)(S) sequence motif, quantitative binding, and molecular modeling of the complex. J Exp Med 176:16811692 53. Kersh GJ, Kersh EN, Fremont DH, Allen PM (1998) High- and low-potency ligands with similar affinities for the TCR: The importance of kinetics in TCR signaling. Immunity 9:817826

Chapter 46 Surface Plasmon Resonance 54. Willcox BE, Gao GF, Wyer JR, Ladbury JE, Bell JI, Jakobsen BK, van der Merwe PA (1999) TCR binding to peptide-MHC stabilizes a flexible recognition interface. Immunity 10:357365 55. Muslin AJ, Tanner JW, Allen PM, Shaw AS (1996) Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 84:889897 56. Houseman BT, Huh JH, Kron SJ, Mrksich M (2002) Peptide chips for the quantitative evaluation of protein kinase activity. Nat Biotechnol 20:270274 57. Bartley TD, Hunt RW, Welcher AA, Boyle WJ, Parker VP, Lindberg RA, Lu HS, Colombero AM, Elliott RL, Guthrie BA, Holst PL, Skrine ID, Toso RJ, Zhang M, Fernandez E, Trail G, Varnum B, Yarden Y, Hunter T, Fox GM (1994) B61 Is a Ligand for the Eck receptor protein-tyrosine kinase. Nature 368:558560 58. James SR, Downes CI, Gigg R, Grove SJA, Holmes AB, Alessi DR (1996) Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. Biochem J 315:709713 59. Ladbury JE, Lemmon MA, Zhou M, Green J, Botfield MC, Schlessinger J (1995) Measurement of the binding of tyrosyl phosphopeptides to Sh2 domains a reappraisal. Proc Natl Acad Sci U S A 92:31993203 60. Floresrozas H, Kelman Z, Dean FB, Pan ZQ, Harper PW, Elledge SJ, Odonnell M, Hurwitz J (1994) Cdk-interacting protein-1 directly binds with proliferating cell nuclear antigen and inhibits DNA-replication catalyzed by the DNA-polymerasedelta holoenzyme. Proc Natl Acad Sci U S A 91:86558659 61. Iemura S, Yamamoto TS, Takagi C, Uchiyama H, Natsume T, Shimasaki S, Sugino H, Ueno N (1998) Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo. Proc Natl Acad Sci U S A 95:93379342 62. Rickles RJ, Botfield MC, Weng ZG, Taylor JA, Green OM, Brugge JS, Zoller MJ (1994) Identification of Src, Fyn, Lyn, Pi3k and Abl Sh3 domain ligands using phage display libraries. Embo J 13:55985604 63. Boll W, Ohno H, Zhou SY, Rapoport I, Cantley LC, Bonifacino JS, Kirchhausen T (1996) Sequence requirements for the recognition of tyrosine-based endocytic signals by clathrin AP-2 complexes. Embo J 15:57895795 64. Sapir T, Elbaum M, Reiner O (1997) Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit. Embo J 16:69776984 65. Heiska L, Alfthan K, Gronholm M, Vilja P, Vaheri A, Carpen O (1998) Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2) - Regulation by phosphatidylinositol 4,5-bisphosphate. J Biol Chem 273:2189321900 66. Li Y, Lee HJ, Corn RM (2007) Detection of protein biomarkers using RNA aptamer microarrays and enzymatically amplified surface plasmon resonance imaging. Anal Chem 79:10821088 67. Rothenhausler B, Knoll W (1988) Surface-plasmon microscopy. Nature 332:615617 68. Jordan CE, Corn RM (1997) Surface plasmon resonance imaging measurements of electrostatic biopolymer adsorption onto chemically modified gold surfaces. Anal Chem 69:14491456 69. Kanda V, Kariuki JK, Harrison DJ, McDermott MT (2004) Label-free reading of microarray-based immunoassays with surface plasmon resonance imaging. Anal Chem 76:72577262 70. Shumaker-Parr JS, Zareie MH, Aebersold R, Campbell CT (2004) Microspotting streptavidin and double-stranded DNA Arrays on gold for high-throughput studies of protein-DNA interactions by surface plasmon resonance microscopy. Anal Chem 76:918929 71. Lyon IA, Musick MD, Smith PC, Reiss BD, Pena DJ, Natan MJ (1999) Surface plasmon resonance of colloidal Au-modified gold films. Sensors and Actuators B-Chemical 54:118124

819

820

K. S. Phillips and Q. Cheng 72. Phillips KS, Wilkop T, Wu JJ, Al-Kaysi RO, Cheng Q (2006) Surface plasmon resonance imaging analysis of protein-receptor binding in supported membrane arrays on gold substrates with calcinated silicate films. J Am Chem Soc 128:95909591 73. Liebermann T, Knoll W (2000) Surface-plasmon field-enhanced fluorescence spectroscopy. Colloids Surfaces a-Physicochem Eng Aspects 171:115130 74. Niemeyer CM (2001) Nanoparticles, proteins, and nucleic acids: biotechnology meets materials science. Angewandte Chemie-International Edition 40:41284158 75. Sigal GB, Bamdad C, Barberis A, Strominger J, Whitesides GM (1996) A selfassembled monolayer for the binding and study of histidine tagged proteins by surface plasmon resonance. Anal Chem 68:490497 76. Brockman JM, Frutos AG, Corn RM (1999). A multistep chemical modification procedure to create DNA arrays on gold surfaces for the study of protein-DNA interactions with surface plasmon resonance imaging. J Am Chem Soc 121:8044 8051 77. Lee HJ, Goodrich TT, Corn RM (2001) SPR Imaging measurements of 1-D and 2-D DNA microarrays created from microfluidic channels on gold thin films. Anal Chem 73:55255531 78. Phillips KS, Han JH, Martinez M, Wang ZZ, Carter D, Cheng Q (2006) Nanoscale glassification of gold substrates for surface plasmon resonance analysis of protein toxins with supported lipid membranes. Anal Chem 78:596603 79. Tawa K, Morigaki K (2005) Substrate-supported phospholipid membranes studied by surface plasmon resonance and surface plasmon fluorescence spectroscopy. Biophy J 89:27502758 80. Szunerits S, Coffinier Y, Janel S, Boukherrouh R (2006) Stability of the gold/ silica thin film interface: Electrochemical and surface plasmon resonance studies. Langmuir 22:1071610722 81. Reimhult E, Zach M, Hook F, Kasemo B (2006) A multitechnique study of liposome adsorption on Au and lipid bilayer formation on SiO2. Langmuir 22:33133319 82. Masson JF, Battaglia TM, Davidson MJ, Kim YC, Prakash AMC, Beaudoin S, Booksh KS (2005) Biocompatible polymers for antibody support on gold surfaces. Talanta 67:918925 83. Phillips KS, Han JH, Cheng Q (2007) Development of a membrane cloaking method for amperometric enzyme immunoassay and surface plasmon resonance analysis of proteins in serum samples. Anal Chem 79:899907 84. He L, Musick MD, Nicewarner SR, Salinas FG, Benkovic SJ, Natan MJ, Keating CD (2000) Colloidal Au-enhanced surface plasmon resonance for ultrasensitive detection of DNA hybridization. J Am Chem Soc 122:90719077 85. Goodrich TT, Lee HJ, Corn RM (2004) Enzymatically amplified surface plasmon resonance imaging method using RNase H and RNA microarrays for the ultrasensitive detection of nucleic acids. Anal Chem 76:61736178 86. Lee HJ, Wark AW, Li Y, Corn RM (2005) Fabricating RNA microarrays with RNA-DNA surface ligation chemistry. Anal Chem 77:78327837