Thiol Self-assembled Monolayers Research Articles

(Invited) Challenges with Electronic Biosensors

The detection of chemical and biological species is critical for applications in healthcare, environmental monitoring, food safety and drug screening. Potentiometric biochemical sensors rely on the specific adsorption of charged analytes that changes the potential of the functionalized sensor surface. The change in surface potential can be measured using a field-effect-transistor (FET) enabling low-cost fabrication, and easy integration with portable readout electronics. The FET concept has previously been applied to numerous (nano-) materials including conventional silicon, nanowires and 2D materials such as graphene. Although many biosensing experiments have been reported, many of the results are not well understood and several key challenges are still limiting their widespread application. In this work, the experimental response from a variety of sensor surfaces and transducers and will be presented.The results show that the choice of the active interface in contact with the electrolyte determines the sensor response and selectivity (the signal) is relatively independent of the transducer. Ideally, protein recognition mechanisms are leveraged to allow only target proteins to attach to the surface, imparting signal selectivity. However, unwanted protein interactions with sensor surfaces cause signal instability and increase false-positive rates. Although commonly used to functionalize the sensing surface, carboxyl-terminated thiol self-assembled monolayers (COOH-SAMs) can have large defect densities, which in turn leads to large non-selective adsorption of proteins to hydrophobic surfaces exposed by these defects. A procedure is developed where the surface of COOH-SAMs is treated before functionalization to improve the reliability and quality of receptor attachment to the sensor surface. Beyond SAM-based sensors, there has been significant interest in biomedical applications of two-dimensional materials such as graphene, including potentiometric sensing. There is conflicting literature on to what extent interaction from the substrate are transmitted through a monolayer, and the subsequent effect on biomolecule interactions are unknown. Therefore, the degree to which the substrate influences graphene-protein interactions is explored. Finally, the choice of the readout transducer (e.g. a graphene transistor) is shown to influence the noise limit, and, hence, the signal-to-noise ratio. Models for diffusion, attachment, and electrical response of these sensors will be described that demonstrates good agreement to experimental data. Despite the current challenges facing label-free, portable biosensors, the work presented here provides a step towards reliable biosensing.

Boosting the Brightness of Thiolated Surface-Enhanced Raman Scattering Nanoprobes by Maximal Utilization of the Three-Dimensional Volume of Electromagnetic Fields.

Self-assembled monolayers (SAMs) of thiols on plasmonic nanoparticles constitute one of the most common methods for fabricating surface-enhanced Raman scattering (SERS) nanoprobes with wide applications. However, this method greatly limits the sufficient utilization of electromagnetic fields derived from plasmon excitation of the nanoparticles, because the thickness of SAMs (<1 nm) is usually much smaller than the attenuation length (>10 nm) of the fields. To overcome this, we propose a three-dimensional (3D) volume-active SERS (VASERS) technique to break the SAM limit, which integrates large amounts of thiol reporters into polydopamine shells on silver nanoparticles via Michael addition and allows sufficient utilization of 3D electromagnetic fields, leading to a dramatic increase in the intensity of the signal of the nanoprobes by about one order of magnitude. We demonstrate the universality of this strategy on various thiol reporters and plasmonic substrates. We also show that orthogonal VASERS nanoprobes with alkyne readout allow for high-precision in vivo tumor targeting and margin delineation.

Characterization of the Reductive Desorption of Self-Assembled Monolayers on Platinum Surfaces

Thiol-based self-assembled monolayers (SAMs) have been widely characterized on gold surfaces, with the desorption potentials of these SAMs being of special interest for nanotechnology and biological applications. However, the study and determination of desorption potentials of thiol SAMs on platinum surfaces has been limited by the hydrogen evolution reaction (HER) catalyzed by the metal, which dominates response signals when studying the system through conventional electrochemical techniques.Through the coupling of electrochemical techniques with fluorescence microscopy, the problem of the HER signal can be avoided in the study of desorption potentials for the platinum-thiol monolayer systems. By using fluorescent thiols, as well as monocrystalline platinum spheres, the desorption potential for different crystallographic orientations and thiol length combinations can be determined. The results obtained show that the desorption of Bodipy C10SH thiols from platinum surfaces occur at more positive potentials in [111] crystallographic orientations, and at more negative potentials at [100] ones. On the other hand, no notable difference was found in the desorption order of Bodipy C16SH from these two orientations.However, the use of fluorescence microscopy for the solution of this problem poses other challenges: the time the thiols need to separate enough from the metallic substrate to not be affected by quenching, as well as the facts that thiols fluoresce less as they dilute and the existing spectral overlap for the molecules, adds difficulties to the establishment of the desorption potentials.Through COMSOL Multiphysics simulations, we try to simulate the systems hereby proposed of platinum with thiol-based SAMs. Using them, the desorption potentials, as well as the monolayer coverage under specific conditions, can be determined. We expect that, with further development of the model, more specific values for these variables can be determined. Figure 1

Comparison between polycrystalline Au and single-crystalline Au(1 1 1) electrodes as the substrate of a cationic organic monolayer based on their anion dependent redox activities

The structures of organic monolayers immobilized on a metal electrode and their functions depend on the substrate surface chemistry and morphology. A better defined crystalline flat electrode usually provides a structurally more ordered organic monolayer, although the use of a single-crystalline electrode costs more for mass production. Because the monolayer structures at both molecular and mesoscopic levels are critical to the functions of the modified electrode, in-depth experimental studies to clarify the relationship between the functions and the surface morphology of the electrode are crucial. In this work, we compared polycrystalline Au (poly-Au) and single-crystalline Au(111) electrodes as the substrates for a redox-active, self-assembled monolayer (SAM) of an alkyl-viologen thiol, 1-(10-mercaptodecyl)-1′-methyl-4,4′-bipyridinium dibromide (MeVC10-SH 2Br−). The voltammetric and electroreflectance measurements were performed at a mirror-polished poly-Au electrode and a flame-annealed single-crystalline Au(111) electrode after their surface modification with a MeVC10-SH monolayer. We found significant differences in the anion effects on the voltammetric behavior between the two substrates, especially in the dependence on anion hydrophobicity. The electroreflectance spectra revealed a tendency that a greater abundance of the viologen radical cation dimers at a Au(111) than that at a poly-Au. A considerable Br− adsorption at the SAM-modified Au(111) electrode was observed because of the loose packing of immobilized MeVC10-SH molecules. We discussed the origins of the contrasting behavior resulting from the difference of the surface.

Non-Destructive Monitoring via Electrochemical NADH Detection in Murine Cells.

Nicotinamide adenine dinucleotide (NADH) is an important cofactor involved in metabolic redox reactions in living cells. The detection of NADH in living animal cells is a challenge. We developed a one-step monitoring method for NADH via an electrocatalytic reaction that uses a surface-modified, screen-printed electrode (SPE) having a redox active monolayer 4′-mercapto-N-phenlyquinone diamine (NPQD) formed by a self-assembled monolayer (SAM) of an aromatic thiol, 4-aminothiophenol (4-ATP). This electrode has a limit of detection (LOD) of 0.49 μM and a sensitivity of 0.0076 ± 0.0006 μM/μA in cell culture media, which indicates that it retains its selectivity. The applicability of this NADH sensor was demonstrated for the first time by cell viability monitoring via NADH-sensing in cell culture supernatants.

Nanoscale Chemical Imaging of Coadsorbed Thiolate Self-Assembled Monolayers on Au(111) by Tip-Enhanced Raman Spectroscopy.

Self-assembled monolayers (SAMs) of thiolates on metal surfaces are of key importance for engineering surfaces with tunable properties. However, it remains challenging to understand binary thiolate SAMs on metals at the nanoscale under ambient conditions. Here, we employ tip-enhanced Raman spectroscopy (TERS) and density functional theory (DFT) calculations to investigate the local information of binary SAMs on Au(111) coadsorbed from an equimolar mixture of p-cyanobenzenethiol (pCTP) and p-aminothiophenol (pATP), including chemical composition, coadsorption behavior, phase segregation, plasmon-induced photocatalysis, and solvation effects. We found that upon competitive adsorption of pCTP and pATP on Au(111) from a methanolic solution, the coadsorption initially occurs randomly and homogeneously; eventually, pATP is replaced by pCTP through the gradual growth of pCTP nanodomains. TERS imaging also allows for visualization of the plasmon-induced coupling of pATP to p,p'-dimercaptoazobenzene (DMAB) and the solvation-induced phase segregation of the binary SAMs into nanodomains, with a spatial resolution of ∼9 nm under ambient conditions. According to DFT calculations, these aromatic thiolates differing only in their functional groups, -CN versus -NH2, show different adsorption energies on Au(111) in vacuum and methanol, and thus, the solvation effect on the adsorption energy of these thiolates in methanol can determine the dispersion state and replacement order of the binary thiolates on Au(111).

Engineered Aurotherapy for the Multimodal Treatment of Glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor, characterized by fatal prognosis and high rates of recurrence. Although there are various treatment strategies such as surgical resection, radiotherapy, and chemotherapy, these traditional approaches still have not improved the survival rates and prolongation. Therefore, there is a pressing requirement for developing novel technologies to combat GBM. Nanoparticle-based GBM therapy can be considered a promising approach to precisely treat tumors with minimal side effects. Among various nanoparticles, gold nanoparticle (AuNP) has been demonstrated to be effective in treating GBM because of its advantages such as easy functionalization due to self-assembled monolayers of thiols, surface plasmon resonance effect on its surface, and relatively low toxicity issues. By using nanoscale (5-100 nm) and facile functionalization with a targeting ligand, AuNP can overcome the obstacles caused by blood-brain barrier, which selectively inhibits AuNP penetration into the brain tumor mass. AuNPs delivered into brain tissue and targeted with GBM have been mostly explored for photothermal therapy and photodynamic therapy, but also investigated in the development of complex therapies including radiotherapy, chemotherapy, and immunotherapy using AuNP-based nanoplatforms. Therefore, the aim of this mini review is to summarize recent works on the AuNPs-based nanoplatforms for treating GBM with a multimodal approach.

Anti-counterfeiting SERS security labels derived from silver nanoparticles and aryl diazonium salts.

The development of anti-counterfeiting inks based on surface-enhanced Raman scattering (SERS) labels have attracted great interest in recent years for their use as security labels in anti-counterfeiting applications. Indeed, they are promising alternatives to luminescent inks, which suffer from several limitations including emission peak overlap, toxicity and photobleaching. Most of the reported SERS security labels developed so far rely on the use of thiolate self-assembled monolayers (SAMs) for the immobilization of Raman reporters on metallic nanoparticle surface. However, SAMs are prone to spontaneous desorption and degradation under laser irradiation, thereby compromising the ink long-term stability. To overcome this issue, we develop herein a new generation of SERS security labels based on silver nanoparticles (Ag NPs) functionalized by aryl diazonium salts, carrying various substituents (-NO2, -CN, -CCH) with distinguishable Raman fingerprints. The resulting SERS tags were fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-vis absorption and SERS. Then, they were incorporated into ink formulations to be printed on polyethylene naphthalate (PEN) substrates, using handwriting or inkjet printing. Proof-of-concept Raman imaging experiments confirmed the remarkable potential of diazonium salt chemistry to design Ag NPs-based SERS security labels.

Structure and stability of 7-mercapto-4-methylcoumarin self-assembled monolayers on gold: an experimental and computational analysis.

Self-assembled monolayers (SAM) of 7-mercapto-4-methylcoumarin (MMC) on a flat gold surface were studied by molecular dynamics (MD) simulations, reference-free grazing incidence X-ray fluorescence (GIXRF) and X-ray photoelectron spectroscopy (XPS), to determine the maximum monolayer density and to investigate the nature of the molecule/surface interface. In particular, the protonation state of the sulfur atom upon adsorption was analyzed, since some recent literature presented evidence for physisorbed thiols (preserving the S-H bond), unlike the common picture of chemisorbed thiyls (losing the hydrogen). MD with a specifically tailored force field was used to simulate either thiol or thiyl monolayers with increasing number of molecules, to determine the maximum dynamically stable densities. This result was refined by computing the monolayer chemical potential as a function of the density with the bennet acceptance ratio method, based again on MD simulations. The monolayer density was also measured with GIXRF, which provided the absolute quantification of the number of sulfur atoms in a dense self-assembled monolayer (SAM) on flat gold surfaces. The sulfur core level binding energies in the same monolayers were measured by XPS, fitting the recorded spectra with the binding energies proposed in the literature for free or adsorbed thiols and thiyls, to get insight on the nature of the molecular species present in the layer. The comparison of theoretical and experimental SAM densities, and the XPS analysis strongly support the picture of a monolayer formed by chemisorbed, dissociated thiyls.

Thermal Stability of Alkanethiolate and Aromatic Thiolate Self-Assembled Monolayers on Au(111): An X-ray Photoelectron Spectroscopy Study

Thermal Stability of Alkanethiolate and Aromatic Thiolate Self-Assembled Monolayers on Au(111): An X-ray Photoelectron Spectroscopy Study

A disposable, wearable, flexible, stitched textile electrochemical biosensing platform

Wearable sensors are a fast growing and exciting research area, the success of smart watches are a great example of the utility and demand for wearable sensing systems. The current state of the art routinely uses expensive and bulky equipment designed for long term use. There is a need for cheap and disposable wearable sensors to make single use measurements, primarily in the area of biomarker detection. Herein we report the ability to make cheap (0.22 USD/sensor), disposable, wearable sensors by stitching conductive gold coated threads into fabrics. These threads are easily functionalised with thiolate self-assembled monolayers which can be designed for the detection of a broad range of different biomarkers. This all textile sensing platform is ideally suited to be scaled up and has the added advantage of being stretchable with insignificant effect on the electrochemistry of the devices. As a proof of principle, the devices have been functionalised with a continuous glucose sensing system which was able to detect glucose in human sweat across the clinically relevant range (0.1–0.6 mM). The sensors have a sensitivity of 126 ± 14 nA/mM of glucose and a limit of detection of 301 ± 2 nM. This makes them ideally suited for biomarker detection in point-of-care sensing applications.

Molecular-Scale Chemical Imaging of the Orientation of an On-Surface Coordination Complex by Tip-Enhanced Raman Spectroscopy.

Metal-organic coordination structures at interfaces play an essential role in many biological and chemical systems. Understanding the molecular specificity, orientation, and spatial distribution of the coordination complexes at the nanometer scale is of great importance for effective molecular engineering of nanostructures and fabrication of functional devices with controllable properties. However, fundamental properties of such coordination systems are still rarely studied directly. In this work, we present a spectroscopic approach on the basis of tip-enhanced Raman spectroscopy (TERS) to investigate cobalt(II) tetraphenyl-porphyrine coordination species on the scale of a single molecule under ambient conditions. Coordination species anchored on gold surfaces modified with pyridine thiol self-assembled monolayers can be spectroscopically distinguished and mapped with ca. 2 nm resolution. In addition, in combination with density functional theory simulations, the adsorption configuration and molecular orientation of the coordination complexes are also revealed using TERS imaging.

Direct electron transfer of fructose dehydrogenase immobilized on thiol-gold electrodes

Direct electrochemical electron transfer (DET) of oxidoreductases has attracted increasing attention in pure and applied bioelectrochemistry (e.g. biosensors and biofuel cells) over the last decades. We report here a systematic study of DET-type bioelectrocatalysis of the membrane-bound redox enzyme fructose dehydrogenase (FDH, Gluconobacter sp.), on variable-length and variably terminated thiol self-assembled monolayers (SAMs) both on Au(111) and nanoporous gold (NPG) electrodes. FDH on Au(111) modified by short-chain moderately hydrophilic 2-mercaptoethanol (BME) SAMs exhibits the highest DET activities and largest DET-capable fraction. Fitting of theoretical polarization curves to the data and homology modeling/docking of FDH offer further mechanistic insight. The dependence of the DET efficiency of FDH on the length and differently terminated carbon chain is systematically presented. The decreased DET rate with increasing chain length is associated with increasingly unfavourable long-range electron tunnelling, and not with lowered enzyme loading. The porous structure of NPG is favorable for FDH bioelectrocatalysis by improving both efficient enzyme orientation and operational stability. Overall, our study maps systematically the controlled local environmental structural flexibility of the Au/SAM/enzyme/solution interface, a paradigm for thiol modified surfaces in biosensors and bioelectronics.

Protein blocking inhibits ambient degradation of self-assembled monolayers for affinity biosensing

The use of a simple protein blocking procedure prior to receptor functionalization is shown to inhibit the oxidation of carboxylic-acid-terminated thiolate self-assembled monolayers (COOH-SAMs) in ambient conditions. This finding has direct implications for the engineering and design of point-of-care and field affinity biosensors. While an abundance of label-free sensor systems utilizing COOH-SAM functional surfaces have been demonstrated, these layers degrade quickly in ambient conditions, severely limiting their shelf life. With gelatin blocking, no surface degradation is observed via X-ray photoelectron spectroscopy nor reductive desorption for 21 days, compared to observable degradation in only one day for an unblocked COOH-SAM. Additionally, unlike a traditional postblocking method that requires the sensor to first be functionalized with active receptor, this blocking procedure occurs directly after COOH-SAM formation and does not prevent the subsequent functionalization of the biosensor. These blocked sensors are shown to maintain surface-plasmon-resonance-based sensing performance for at least one week. Additionally, the blocking technique for degradation prevention is shown to even outperform COOH-SAM storage in N2.

Comparative study of structural order, thermal desorption behavior, and work function change of self-assembled monolayers of pentafluorobenzenethiols and tetrafluorobenzenethiols on Au(1 1 1)

The surface and interface structures, thermal desorption behaviors, and electronic properties of pentafluorobenzenethiol (PFBT) and tetrafluorobenzenethiol (TFBT) self-assembled monolayers (SAMs) on Au(111) formed at different vapor deposition temperatures (298, 323, and 348 K) were examined to understand the effect of dipole directions in fluorinated aromatic thiol SAMs using scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), thermal desorption spectroscopy (TDS), and Kelvin probe (KP) measurements. Molecular-scale STM observations revealed that PFBT SAMs on Au(111) had a well-ordered phase with a c(2 × √3) structure at 348 K, whereas TFBT SAMs showed a well-ordered phase with a (2√3 × 8√2)R30° structure at 323 K.TDS and XPS measurements also demonstrated thatPFBT and TFBT SAMs showed significantly different thermal desorption behaviorsand interface structures due toopposite directions of molecular dipole moments. The KP measurements showed that the extent of the work function change of SAM-modified Au substrates was lowest in most highly-ordered PFBT and TFBT SAMs formed at 348 K and 323 K, respectively, regardless of chemisorbed surface coverage. These findings revealed that the degree of structural order of SAMs is a more significant factor in causing the depolarization effect rather than chemisorbed surface coverage.

Fast Photo-Chrono-Amperometry of Photosynthetic Complexes for Biosensors and Electron Transport Studies.

Photosynthetic reactions in plants, algae, and cyanobacteria are driven by photosystem I and photosystem II complexes, which specifically reduce or oxidize partner redox biomolecules. Photosynthetic complexes can also bind synthetic organic molecules, which inhibit their photoactivity and can be used both to study the electron transport chain and as herbicides and algicides. Thus, their development, characterization, and sensing bears fundamental and applied interest. Substantial efforts have been devoted to developing photosensors based on photosystem II to detect compounds that bind to the plastoquinone sites of this complex. In comparison, photosystem I based sensors have received less attention and could be used to identify novel substances displaying phytotoxic effects, including those obtained from natural product extracts. We have developed a robust procedure to functionalize gold electrodes with photo- and redox-active photosystem I complexes based on transparent gold and a thiolate self-assembled monolayer, and we have obtained reproducible electrochemical photoresponses. Chronoamperometric recordings have allowed us to measure photocurrents in the presence of the viologen derivative paraquat at concentrations below 100 nM under lock-in operation and a sensor dynamic range spanning six orders of magnitude up to 100 mM. We have modeled their time course to identify the main electrochemical processes and limiting steps in the electron transport chain. Our results allow us to isolate the contributions from photosystem I and the redox mediator, and evaluate photocurrent features (spectral and power dependence, fast transient kinetics) that could be used as a sensing signal to detect other inhibitors and modulators of photosystem I activity.

Temperature dependence of resistivity increases induced by thiols adsorption in gold nanosheets

By utilizing stable thiol self-assembled monolayers (SAMs) on gold (Au) nanosheets, we investigated the temperature dependence of the amount of resistivity increases by SAM modification. increased with increasing temperature from 5 to 375 K in all the measured nanosheets for various thicknesses (9–20 nm). We consider from the DFT calculation that the temperature dependence originates from unoccupied states of sulfur atoms above the Fermi level of Au. The available unoccupied states increase at higher temperatures, which enhances scattering rates and thus increases the resistivity. Furthermore, we calculated the temperature dependence of using the Bloch–Grüneisen theory and Fuchs–Sondheimer (FS) model. Based on the results, we conclude that for ultra-thin metal films, the temperature-dependent specularity parameter which represents the fraction of electrons scattered specularly should be introduced into the conventional FS model to predict over a wide temperature range.

Quantitative analysis of weak current rectification in molecular tunnel junctions subject to mechanical deformation reveals two different rectification mechanisms for oligophenylene thiols versus alkane thiols.

Metal-molecule-metal junctions based on alkane thiol (CnT) and oligophenylene thiol (OPTn) self-assembled monolayers (SAMs) and Au electrodes are expected to exhibit similar electrical asymmetry, as both junctions have one chemisorbed Au-S contact and one physisorbed, van der Waals contact. Asymmetry is quantified by the current rectification ratio RR apparent in the current-voltage (I-V) characteristics. Here we show that RR < 1 for CnT and RR > 1 for OPTn junctions, in contrast to expectation, and further, that RR behaves very differently for CnT and OPTn junctions under mechanical extension using the conducting probe atomic force microscopy (CP-AFM) testbed. The analysis presented in this paper, which leverages results from the previously validated single level model and ab initio quantum chemical calculations, allows us to explain the puzzling experimental findings for CnT and OPTn in terms of different current rectification mechanisms. Specifically, in CnT-based junctions the Stark effect creates the HOMO level shifting necessary for rectification, while for OPTn junctions the level shift arises from position-dependent coupling of the HOMO wavefunction with the junction electrostatic potential profile. On the basis of these mechanisms, our quantum chemical calculations allow quantitative description of the impact of mechanical deformation on the measured current rectification. Additionally, our analysis, matched to experiment, facilitates direct estimation of the impact of intramolecular electrostatic screening on the junction potential profile. Overall, our examination of current rectification in benchmark molecular tunnel junctions illuminates key physical mechanisms at play in single step tunneling through molecules, and demonstrates the quantitative agreement that can be obtained between experiment and theory in these systems.

Pronounced Solvent Effect on the Composition of Binary Self-Assembled Monolayers with Embedded Dipole Moments

The formation and properties of binary thiolate self-assembled monolayers (SAMs), comprised of precursors featuring a short heteroaromatic backbone, consisting of a nonpolar phenyl ring and a polar...

Interfacial Structure and Function of Nano-Structured Membranes of Newly Synthesized Phosphorylcholine Derivatives on Single Crystal Electrodes

Properties of modified surface for biosensing interface are recognized as important subjects to develop methodologies in bio-related analysis and techniques. Therefore, various surface modification materials to fabricate biosensing interface have been synthesized and studied on properties of modified surface of gold,1-4 carbon,5 silicon6 and some polymer7,8 substrates for application to biosensor and micro flow analytical system. The non-specific adsorption of proteins that occurs during analysis of biomolecules often has a serious detrimental effect on selectivity and detection limit, and research on surface modification materials has attracted great interest with a view to avoiding the interference caused by the non-specific adsorption of proteins. The properties of polyethylene glycol (PEG) such as flexibility, chemical stability, water solubility, and low cytotoxicity make it a versatile surface modification material. The most attractive property of PEG is its suppressive effect on the non-specific adsorption of proteins. While polymers consisting of the ethylene glycol moiety have been studied extensively, it has also been reported that self-assembled monolayers (SAMs) of oligoethylene glycol-alkane thiols suppress the non-specific adsorption of proteins in a similar way to surfaces modified with PEG. Our previous work showed that SAMs of oligoethylene glycol–alkane thiols effectively suppressed the non-specific adsorption of proteins allowing us to realize the high performance detection of proteins.1 On the other hand, phosphorylcholine derivatives are other promising candidates for suppressing the non-specific adsorption of proteins because the phosphorylcholine group is one of the primary lipid components of plasma membranes. Although SAMs of phosphorylcholine-alkane thiols were also reported to suppress the non-specific adsorption of proteins, there have been relatively few studies related to SAMs of phosphorylcholine-alkane thiols compared with those on SAMs of oligoethylene glycol–alkane thiols. Therefore, we are interested in the properties of phosphorylcholine SAMs. It was found that newly synthesized phosphorylcholine-alkane thiols bearing the oligoethylene glycol moiety, namely phosphorylcholine–oligoethylene glycol–alkane thiols, formed SAMs on gold surfaces and suppressed fibrinogen adsorption more effectively than the corresponding oligoethylene glycol–alkane thiols.2 The incorporation of oligoethylene glycol moieties in phosphorylcholine-alkane thiols enhanced the suppressive effect on concanavalin A adsorption but not on fibrinogen adsorption. Furthermore, we studied the newly synthesized zwitterion–alkane thiol SAMs which have phosphorylcholine, inverse phosphorylcholine and sulfobetaine terminal groups as shown in Figure 1, and repot here mainly the results on the interfacial structure and function of the phosphorylcholine-alkane thiol SAMs on a single crystal Au(111) electrode in solution. An electrochemical scanning tunneling microscope (EC-STM) was used to observe surface feature of phosphorylcholine-dodecanethiol (C12PC) SAMs on Au(111) in 0.1M HClO4, and mostly flat terrace surface with the surface roughness less than 0.3 nm was observed in a wide scan area, indicating that the molecules were closely packed. A typical high-resolution EC-STM images of C12PC SAM on Au(111) was presented in Figure 2. Bright spots aligned toward √3 directions were clearly observed with spacing of 0.5 nm, corresponding to individual C12PC molecules. The molecular arrangement was assigned to (√3 x 3√3)R30° structure with two C12PC molecules in the lattice. The surface coverage of the monolayer was 2/9, which is consistent with that from the charge of electrochemical reductive desorption process with an assumption of one-electron reaction. In the case of the phosphorylcholine–diethylene glycol–alkane thiols (C12O2PC) SAMs, the monolayer exhibited the double-striped (√3 x 3√3)R30° structure with a molecular coverage of 2/9, where every three C12O2PC molecular rows was missing. In comparison with C12PC and C12O2PC SAMs, the molecular arrangement of C12PC would be (√3 x 3√3)R30°-2C12PC missing row structure, which is the same as that of the C12O2PC SAM, because of bulkiness of phosphorylcholine head group. A detailed analysis of the surface structure will be discussed with the function suppressing the non-specific adsorption of proteins.References(1) Y. Sato, K. Yoshioka, M. Tanaka, T. Murakami, M. N.Ishida, N. Niwa, Chem. 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