Plasmonic Imaging of Electrochemical Reactions ... - ACS Publications

Sep 23, 2016 - Currently he is an associate research professor in the School of Chemistry and Chemical Engineering at Nanjing University (NJU), China...
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Plasmonic Imaging of Electrochemical Reactions of Single Nanoparticles Published as part of the Accounts of Chemical Research special issue “Nanoelectrochemistry”. Yimin Fang,† Hui Wang,† Hui Yu,† Xianwei Liu,‡ Wei Wang,*,† Hong-Yuan Chen,*,† and N. J. Tao*,† †

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China ‡ Department of Chemistry, University of Science & Technology of China, Hefei 230026, China CONSPECTUS: Electrochemical reactions are involved in many natural phenomena, and are responsible for various applications, including energy conversion and storage, material processing and protection, and chemical detection and analysis. An electrochemical reaction is accompanied by electron transfer between a chemical species and an electrode. For this reason, it has been studied by measuring current, charge, or related electrical quantities. This approach has led to the development of various electrochemical methods, which have played an essential role in the understanding and applications of electrochemistry. While powerful, most of the traditional methods lack spatial and temporal resolutions desired for studying heterogeneous electrochemical reactions on electrode surfaces and in nanoscale materials. To overcome the limitations, scanning probe microscopes have been invented to map local electrochemical reactions with nanometer resolution. Examples include the scanning electrochemical microscope and scanning electrochemical cell microscope, which directly image local electrochemical reaction current using a scanning electrode or pipet. The use of a scanning probe in these microscopes provides high spatial resolution, but at the expense of temporal resolution and throughput. This Account discusses an alternative approach to study electrochemical reactions. Instead of measuring electron transfer electrically, it detects the accompanying changes in the reactant and product concentrations on the electrode surface optically via surface plasmon resonance (SPR). SPR is highly surface sensitive, and it provides quantitative information on the surface concentrations of reactants and products vs time and electrode potential, from which local reaction kinetics can be analyzed and quantified. The plasmonic approach allows imaging of local electrochemical reactions with high temporal resolution and sensitivity, making it attractive for studying electrochemical reactions in biological systems and nanoscale materials with high throughput. The plasmonic approach has two imaging modes: electrochemical current imaging and interfacial impedance imaging. The former images local electrochemical current associated with electrochemical reactions (faradic current), and the latter maps local interfacial impedance, including nonfaradic contributions (e.g., double layer charging). The plasmonic imaging technique can perform voltammetry (cyclic or square wave) in an analogous manner to the traditional electrochemical methods. It can also be integrated with bright field, dark field, and fluorescence imaging capabilities in one optical setup to provide additional capabilities. To date the plasmonic imaging technique has found various applications, including mapping of heterogeneous surface reactions, analysis of trace substances, detection of catalytic reactions, and measurement of graphene quantum capacitance. The plasmonic and other emerging optical imaging techniques (e.g., dark field and fluorescence microscopy), together with the scanning probebased electrochemical imaging and single nanoparticle analysis techniques, provide new capabilities for one to study single nanoparticle electrochemistry with unprecedented spatial and temporal resolutions. In this Account, we focus on imaging of electrochemical reactions at single nanoparticles.

1. INTRODUCTION

much of today’s understanding of electrochemistry, it lacks spatial resolution required to probe local electrochemical reactions, which is critical to resolve heterogeneous reactions that usually occur in practical systems.

Electrochemical reactions take place at the interface between an electrode and electrolyte, which involves electron transfer between a chemical species and the electrode. A direct and powerful approach to study the reactions is to measure the current, charge, or other related quantities associated with the electron transfer electrically. While this approach has provided © 2016 American Chemical Society

Received: July 4, 2016 Published: September 23, 2016 2614

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adsorbed on an electrode or oxidation/reduction of the electrode surface itself, and the other involves chemical species in the electrolyte. We next describe plasmonic imaging of double layer charging and related interfacial impedance. We refer to the electrochemical current and impedance imaging modes as plasmonics-based electrochemical current microscopy (PECM) and plasmonics-based electrochemical impedance microcopy (PEIM), respectively. Finally, we conclude by discussing the current limitations and future directions of the plasmonics-based electrochemical imaging techniques.

Microelectrodes have been invented to probe local electrochemical reactions and found important applications, e.g., recording neurotransmitter release in brain1,2 By scanning the microelectrode, it is possible to create an image of local electrochemical reactions on a surface.3 Since the invention of scanning electrochemical microscopy (SECM),3 several ingenious electrochemical imaging techniques have been developed, each using an electrode or pipet as a probe.4−8 This scanningprobe based approach has led to important discoveries and applications.4,9 The use of a nanoscale probe provides high spatial resolution (from 1 nm to tens of nm) for studying single nanoparticle electrochemistry,7,10,11 but mechanical scanning of the probe and detection of a small current compromise the imaging speed to approximately minutes. Instead of measuring an electrical signal (e.g., current and charge), one could also study electrochemical reactions via optical detection.12 Studies have found that electrochemical reactions are accompanies by changes in optical properties, such as reflectivity of an electrode.13−15 However, the reflectivity changes are often small. To amplify the optical signal, an interferometric method has been used to study electrochemical reactions via detecting changes in the refractive index in the electrolyte.16−19 The interferometric method measures both changes on the electrode surface and in the electrolyte, which cannot be easily deconvoluted. Several surface sensitive optical detection and imaging technologies have been developed. For example, surface plasmon resonance (SPR) can measure electrochemical reactions on or near electrode surfaces with a distance of ∼200 nm.20−28 Dark field29−35 and holography36 are particularly sensitive to electrochemical reactions on metallic nanoparticles via local surface plasmon resonance (LSPR).37−39 Surface enhanced raman spectroscopy (SERS) provides molecular vibration information and chemical specificity of molecules on electrodes.40−42 Local electrochemical current can be probed by depositing colloidal particles on an electrode as the electric current (field) on the electrode changes the particle-surface distance.43 Another optical method is fluorescent microscopy, which provides super-resolution and single molecule detection capabilities for studying electrochemical reactions.29,44,45 This Account discusses a plasmonics-based approach for imaging electrochemical phenomena. Unlike the optical methods described above, it determines electrochemical current and other electrical properties quantitatively from the plasmonic signals. Electrochemical current includes faradic and nonfaradic (double layer charging) components, both are imaged from the plasmonic signals. This approach allows us to apply the traditional electrochemical methods, such as voltammetry and chronoamperometry, to study heterogeneous reactions, analyze the data with established electrochemical theories, and compare the results with the traditional electrical measurements. Using an optical microscope, bright/dark field and SPR images can be obtained simultaneously together with the electrochemical images. The new imaging capabilities have been applied to image heterogeneous surface reactions,46,47 mammalian48−54 and bacterial cells,55,56 subcellular organelles,57 viruses,58 single DNA molecules,59 and protein microarrays.60,61 This Account will focus on nanomaterials using examples primarily from our laboratory. We first set the stage by reviewing SPR phenomenon and imaging.62 We then discuss the basic principle of plasmonic imaging of electrochemical current. Two types of electrochemical reactions are considered: one involves molecules

2. BASIC PRINCIPLE OF SURFACE PLASMON RESONANCE IMAGING Surface plasmons are collective oscillations of free electrons near the surface of a metal film (electrode), typically deposited on a glass slide, which can be excited using light with an appropriate incident angle (resonant angle) (Figure 1a).63,64 At

Figure 1. Principle of SPR imaging. (a) Stratified medium model of SPR imaging. (b) Scattering model of SPR imaging showing that a nanoparticle image contrast arises from the interference of scattered surface plasmon and reflected light. (c) Simulated (top) and experimental (bottom) SPR images of a nanoparticle at different incident angles. Reproduced with permssion from ref 65. Copyright 2014 American Chemical Society.

the resonant angle, light is absorbed by surface plasmons, leading to a decrease in the reflected light intensity that is imaged with an optical system. The resonant angle (θR) is given by sin(θR ) = 2615

ε1εm (ε1 + εm)ε2

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Accounts of Chemical Research where ε1, ε2, and εm are the dielectric constants of the electrolyte, glass slide, and metal film, respectively. An electrochemical reaction at the electrode−electrolyte interface converts a reactant into a product near the electrode surface. Because the optical polarizabilities of the reactant and product are usually different, we expect a change in the electrolyte refractive index (ε1) accompanying the electrochemical reaction, thus leading to a shift in the resonant angle. A simple method to detect the resonant angle shift is to fix the incident angle near the resonant angle, and measure the intensity change in the reflected light. The above theory captures the basic concept of SPR, but it assumes a uniform surface, and thus does not apply to heterogeneous surfaces, such as nanoparticles on an electrode surface. One way to understand the SPR image of individual nanoparticles is to treat each nanoparticle as a source that scatters the plasmonic waves propagating on the electrode surface (Figure 1b).65,66 When light is incident on the metal film, it is partially reflected (Er) at the interface of glass/metal and partially penetrated into the metal film as an evanescent wave, which excites surface plasmons (Esp). The total reflected light intensity recorded by the camera (ISPR) is the superposition of the reflected field and scattered plasmonic field in the direction of reflection67,68 given by ISPR ∼ |Er + βEsp|2

(2)

where β is a constant that describes the scattering strength. In the limit of weak scattering (β is small), eq 2 becomes * + Er*Esp) ISPR ∼ |Er|2 + β(ErEsp

(3)

where the first term produces a uniform SPR intensity with resonant angle described by eq 1,55 and the second term describes the image of the nanoparticle, which gives rise to a distinct parabolic pattern in the SPR image. The above theory predicts different image contrasts at different incident angles, which are in excellent agreement with the measured images (Figure 1c). An electrochemical reaction at the nanoparticle changes the surrounding refractive index, thus the scattering strength (β), which leads to a change in the SPR image contrast of the nanoparticle.

3. PLASMONICS-BASED ELECTROCHEMICAL CURRENT IMAGING We show below that the electrochemical current associated with the oxidation or reduction of chemical species on an electrode can be obtained from the plasmonic signals. This allows us to obtain the electrochemical current image without electrically measuring the current, and thus perform local voltammetry and chronoamperometry in a manner similar to the traditional electrochemical measurements. An electrochemical reaction may involve chemical species dissolved in the electrolyte, or adsorbed on the electrode, or oxidation/ reduction of the electrode surface itself. We consider each case below.

Figure 2. (a) Schematic illustration of PECM. (b) CVs measured by the traditional electrochemical method (red line) and by PECM (open circles) of a bare gold electrode. The electrolyte is 0.25 M phosphate buffer containing 10 mM Ru(NH3)63+, and the potential sweep rate is 0.1 V/s. (c) PECM images of a fingerprint at different potentials recorded during continuous cycling of the electrode potential between −0.10 and −0.34 V at a rate of 0.1 V/s. The electrolyte is 0.25 M phosphate buffer containing 10 mM Ru(NH3)63+. Reproduced with permssion from ref 46. Copyright 2010 American Association for Advancement of Science.

diffusion distance is much larger than the penetration distance, then the SPR image intensity (ISPR) can be expressed as69,70

3.1. Electrochemical Reactions of Chemical Species in Electrolytes

ISPR (x , y , t ) ≈ B[αOCO(x , y , t )|s + αR C R (x , y , t )|s ]

Associated with SPR is an evanescent field that penetrates into the electrolyte over a distance of ∼200 nm from the electrode surface, which makes SPR sensitive to the refractive index of the electrolyte within the evanescent field (Figure 2a). If the

(4)

where CO(x, y, t)|s and CR(x, y, t)|s are the concentrations of the oxidized and reduced species on the electrode surface, αO and αR are their local refractive indices per unit concentration, respectively, and B is a constant determined by the plasmonic 2616

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Figure 3. Single Pt nanoparticle’s electrocatalytic reaction. (a−f) PECM current density image of a single Pt nanoparticle at potentials, −0.05, −0.36, −0.40, −0.50, −0.4, and −0.05 V, respectively. Scale bar:, 3 μm. (g) CV of the single Pt nanoparticle obtained by integrating the current density over the scattering pattern, including the tail. Reproduced with permssion from ref 73. Copyright 2012 Nature Publishing Group.

field enhancement and the optics setup, including wavelength of light, and refractive indices of the glass, metal and electrolyte. The diffusion distance is ∼ Dt , where D is diffusion coefficient and t is the time scale of measurement (e.g., time required for one potential cycle in voltammetry). If assuming that D ∼ 10−9 m2/s (for typical ions and molecules in aqueous electrolytes) and t ∼ 1 ms (i.e., 1000 V/s potential scanning rate), then the diffusion distance is >1 μm, much greater than the penetration length of the evanescent field (∼200 nm), so eq 4 holds. However, for extremely large molecules, e.g., human immunoglobulin G (MW = 153 kDa), D = 4 × 10−11 m2/s,71 the diffusion distance over 1 ms is ∼200 nm, comparable to the evanescent field penetration distance. In this case, eq 4 holds when the measurement time is slower than 1 ms. Combining eq 4 with diffusion equation and boundary conditions allows us to relate electrochemical current density (J) to SPR image intensity by46 ̃ (x , y , s)] J(x , y , t ) = bnF 3−1[s1/2ΔISPR

[B(αRDR−1/2

has been used to study heterogeneous electrochemical reactions.46 One example is imaging of electrochemical reactions of Ru(NH3)63+ on Au electrode covered with fingerprint, where the image contrast arises from local variations in the electrochemical current density (Figure 2c). The cyclic voltammograms (CVs) obtained with PECM resemble those obtained with the traditional electrochemical measurement (Figure 2b). However, when comparing the plasmonic CVs with those recorded with the traditional potentiostat, several details must be considered. First, PECM images local CVs, while the traditional electrical method measures CV of the entire electrode surface exposed to the electrolyte. Second, like the traditional CV, the plasmonic CV contains both faradaic and nonfaradaic currents, but the two currents are related to the plasmonic image intensity by different relations (eqs 5−7). We will return to the second point later. Another example is the study of electrocatalytic reactions of single Pt nanoparticles.73 Electrocatalysis represents one of the most useful applications of nanoparticles, but the study to date has been largely limited to measuring the average electrochemical current of many nanoparticles on an electrode. This ensemble approach has its limitations because the electrocatalytic activities depend on the size, shape, structure and chemical composition of the nanoparticles,74 and there is a need to measure electrochemical reactions of single nanoparticles.75,4,76−78

(5)

αODO−1/2)]−1,

where b = − n is the mole number of electrons transferred in the reaction, F is the Faraday ̃ constant, 3 −1 stands for inverse Lapalace transform, and ΔISPR is the Lapalace transform of the local SPR image intensity. By applying different potential waveforms to the electrode, eq 5 allows us to obtain different types of voltammograms, including cyclic and square wave voltammograms,46,72 by recording the SPR image while changing the potential (Figure 2b). PECM 2617

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Figure 4. (a−e) Snapshots of plasmonic images of three Ag nanoparticles during a typical collision-oxidation process. Scale bars (black): 10 μm. (f) Plasmonic image intensity vs nanoparticle size by dynamic light scattering (black dots) and AFM (red dots). (g) Transient plasmonic image intensity curves of the three individual Ag nanoparticles shown in (a)−(e). (h) Transient electrochemical current of the Ag nanoparticles obtained from the plasmonic image intensity. Reproduced with permssion from ref 79. Copyright 2014 American Chemical Society.

3.2. Electrochemical Reactions of Adsorbed Species and Electrode Surfaces

We show here that PECM can image and quantify electrocatalytic reactions of single nanoparticles by cycling the electrode potential.73 At −0.05 V, no electrocatalytic reaction takes place and the current density is zero everywhere (Figure 3a). Decreasing the potential to −0.36 V, the image begins to show contrast near the center of the frame, where a nanoparticle is located. The current image contrast is negative, representing cathodic current for electrocatalytic reduction of hydrogen. The image contrast increases as the potential decreases, and reaches a maximum at −0.5 V (Figure 3b−d). Sweeping the potential positively, the image contrast decreases and eventually diappears as the hydrogen reduction diminishes at positive potentials (Figure 3e,f). The CVs for the single nanoparticle show a current of ∼ −5 nA at −0.5 V (Figure 3g). PECM provides size information from the simultaneously recorded SPR image with high throughput, which allows statistical analysis of nanoparticles with different sizes and electrocatalytic activities.73

The electrochemical reactions discussed above involve chemical species in the electrolyte, where mass transport (diffusion) is important. When a chemical species is adsorbed on the electrode, mass transport is no longer present. In this case, the electrochemical current density (J) is related to local SPR image intensity by J (x , y , t ) = γ

dISPR (x , y , t ) nF αred − αox dt

(6)

where β is a constant. Note that eq 6 also applies to the case where the electrochemical reactions involve the electrode surface itself, such as oxidation of the surface atoms. PECM has imaging capability, which allows study of individual nanorparticles simutaneously. One example is the study of electrochemical oxidation of single Ag nanoparticles (Figure 4).79 The nanoparticle size information is obtained from the conventional SPR images (Figure 4f), and the electrochemical oxidation current is provided from PECM with 2618

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the Dirac point, such that the quantum capacitance is small, and thus, dominates the total interfacial capacitance of graphene.89−92 The small interfacial capacitance is also responsible for the relative small double layer charging current of glassy carbon and other carbon-based electrodes (compared to metal electrodes), which helps reducing the background charging current for analytical applications. Due to the heterogeneous nature of most graphene samples, mapping the local quantum capacitance is necessary for a complete picture of graphene interfacial capacitance. Scanning gate microscopy93,91 and scanning single-electron transistor microscopy94,95 can probe local surface conductance and charge of graphene, but the use of a scanning probe limits their applications, especially for imaging interfacial capacitance in aqueous solutions and electrolytes. To measure the quantum capacitance of graphene, a periodic potential modulation with amplitude, ΔV, and angular frequency, ω, is applied to the electrode, which creates a periodic modulation in the charging current density, Jd(x, y, t), imaged by PEIM (eq 7).83 A capacitance image is obtained by performing Fourier transform on the SPR image intensity for each pixel, and the capacitance image is related to the amplitude of Fourier transform of the local SPR imaging intensity, ΔISPR(x, y, ω), according to c(x, y, ω) = αΔISPR(x, y, ω)/ΔV. Because Fourier transform rejects noise at frequencies other the potential modulation frequency, this method helps improve the signal-to-noise ratio of the capacitance image. Figure 5a shows the SPR (left) and bright-field (right) images of a single layer graphene, and Figure 5b shows the local interfacial capacitance of the graphene sample at the Dirac point.83 The graphene interfacial capacitance measured by PEIM consists of two major contributions: double layer capacitance (CEDL) and quantum capacitance (CG). The two contributions can be modeled as two capacitors in series, and the quantum capacitance of graphene is given by, 1 1 1 = C − C , where C is the measured interfacial capaciC

eq 6 (Figure 4a−e). The collision of individual Ag nanoparticles with the electrode leads to transient electrochemical oxidation current spikes (Figure 4g,h), and voltammetry performed on single nanoparticles immobilized on the electrode provides additional information about the reaction rate vs electrode potential. Statistical analysis of the nanoparticles reveals a large variability in the oxidation kinetics, which is due to the variability in the surface chemistry of the nanoparticles, although the average kinetics still follows the Butler−Volmer equation.

4. PLASMONICS-BASED ELECTROCHEMICAL IMPEDANCE IMAGING We have shown that PECM works by imaging changes in the reactant/product concentrations associated with electrochemical reactions on the electrode, which is thus limited to the detection of faradic current. The traditional electrochemical methods measure both faradaic current and double layer charging (polarization) current. We show below that PEIM is also capable of imaging local double layer charging current. SPR is extremely sensitive to refractive index near a metal surface, which is a key for PECM described above. SPR is also sensitive to surface charge density because surface plasmon frequency depends on electron density in the metal film (electrode), which affects the dielectric constant of the electrode (εm), and thus the resonance angle, according to eq 1. By measuring time dependent SPR imaging intensity, double layer charging current and thus interfacial impedance can be obtained, leading to PEIM. The double layer charging current density is directly related to the SPR image intensity according to80 Jd (x , y , t ) = α

d ISPR (x , y , t ) dt

(7)

This equation shows that like chemical reactions on electrode surfaces (eq 6) local double layer charging current can also be determined from the time derivative of SPR image intensity. Quantitative impedance analysis from PEIM requires α in eq 7, which can be determined with the Drude model (free electron gas model), or other more sophisticated models. Alternatively, it can be obtained by experimental calibration. We note that α nF in eq 7, β α − α in eq 6 and b in eq 5 are all different, and one red

G

EDL

tance. CEDL can be obtained from the interfacial capacitance in the area of bare gold surface, which is about 25 μF/cm2 in 0.2 M NaF. Using this value, local graphene quantum capacitance is obtained from the interfacial capacitance imaged with PEIM. The average quantum capacitance is 3−5 μF/cm2 for the single layer graphene at the Dirac point, which is small compared to the double layer capacitance. This observation verifies the conclusion that the quantum capacitance dominates the total interfacial capacitance of graphene. There is a significant deviation between the measured and calculated quantum capacitance values at the Dirac point, which is attributed to charged impurities in the real graphene samples. From the quantum capacitance images measured with PEIM, local variation in the charged impurities is determined (Figure 5c).83 This level of detailed information is difficult to obtain with other technologies.

ox

must consider their relative contributions to plasmonic CVs. The principle of PEIM has been validated by comparing the impedance with that simultaneously measured by the traditional electrochemical method.61 PEIM has been applied to imaging cells,51,81 and protein microarrays.60,82 Here we describe two examples related to nanomaterials. One is PEIM mapping of local quantum capacitance and charge impurities of graphene,83 and the second example is PEIM detection of nanoparticle-functionalized electrodes for sensing applications.84,85 4.1. Graphene Local Quantum Capacitance

4.2. Nanoparticle Oscillator-Modified Electrodes for Sensing Applications

Measuring the capacitance of graphene is relevant to developing electronic and energy storage applications, such as supercapacitors.86−88 The energy storage capacity of the supercapacitors is determined by the specific surface area and capacitance of graphene. The former is extremely large for atomically thin graphene, but the latter is nearly zero at the Dirac point (potential of zero charge). This is because, unlike most other materials, the density of states of graphene is zero at

The basic concept of PEIM is to measure the SPR image contrast change in response to an applied potential. In the example discussed above, the SPR image contrast change arises from surface charge density change associated with potential modulation, which is directly related to the double layer charging current density according to eq 7. However, the concept of PEIM is more general because the response in the SPR image contrast to an applied potential may arise from 2619

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Figure 5. Imaging of local quantum capacitance of graphene with PEIM. (a) Plasmonic image (left) and bright field image (right) of a single layer graphene. (b) Quantum capacitance of single layer graphene (outlined with red dashed line). (c) Capacitance distributions of the single layer graphene and the surrounding bare Au area. Reproduced with permssion from ref 83. Copyright 2015. Wiley VCH. Figure 6. Self-assembled nano-oscillators and PEIM detection. (a) Schematic illustration of nano-oscillators self-assembled on a Auelectrode and plasmonic imaging of the oscillation. Each nanooscillator consists of a AuNP and a molecular bridge attached to the electrode. (b) Oscillation of a nano-oscillator (blue) and corresponding driving electric field (red) in time domain. Snapshots of several plasmonic images during the oscillation are shown (top). Scale bar: 5 μm. (c) Average effective charges of different nanoparticles. Applied electric field has amplitude of 22.75 V/m and frequency of 5 Hz. Buffer: 10 mM PBS solution. Molecular bridge: PEG with molecular mass of 3400 g/mol. Scale bar: 5 μm. Reproduced with permssion from ref 84. Copyright 2014 American Chemical Society.

sources other than double layer charging. For example, modification of an electrode with a layer of functionalized polymer that shrinks or expands with the applied potential also leads to a large PEIM contrast change. This effect has been used as a signal amplification mechanism to detect small molecules that bind to the polymer.60,82 Detecting small molecules binding kinetics is an important (e.g., most drugs are small molecules) but difficult task. In addition to polymer layers, one can also functionalize the electrode with a layer of nanoparticles.84 Each nanoparticle is tethered to the electrode with a DNA or other polymers (Figure 6a). When the nanoparticle is charged, it oscillates with the applied potential due to electrostatic force, leading to large signal amplification in the PEIM image (Figure 6b). We have shown that the PEIM image contrast of the nano-oscillators is extremely sensitive to the charge on the nanoparticle, which can detect the effective charge of the nanoparticle with a detection limit of ∼0.18 electrons (Figure 6c). This capability has been used to detect binding of molecules (charged) to the nanoparticles functionalized with molecular receptors.84 A useful application of the nano-oscillator electrode is to detect post-translational modification of proteins, such as

phosphorylation,85 immobilized on the nanoparticles. Phosphorylation is the addition of a phosphate group to a protein at a specific site assisted with enzymes (kinases), which is involved in almost all basic cellular processes, including cell metabolism, growth, division, differentiation, motility, and signaling. It is also closely related to various diseases, such as diabetes, neurodegenerative diseases, and cancers.96 The traditional detection of phosphorylation relies on antibodies, which is limited to only a small number of proteins that have antibodies. Furthermore, the antibody approach cannot provide kinetic 2620

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Accounts of Chemical Research information on phosphorylation. We have studied the kinetics of phosphorylation in real time, from which Michaelis constant and catalytic rate constant are determined without antibodies. Because an array of nano-oscillators can be self-assembled on an electrode with high density and interrogated individually, the method promises potential high throughput detection of molecular binding and biochemical processes (e.g., phosphorylation) that involve charge changes.

chemical imaging capabilities,98 which opens the door to new opportunities for studying electrochemical phenomena.

5. CONCLUSIONS The plasmonics-based electrochemical imaging techniques described in this Account provide new capabilities to study local electrochemical phenomena, which are needed for elucidating heterogeneous surface reactions, characterizing single nanoparticle electrocatalytic activities, and providing electrochemical detection for microarrays. Compared to other optical detection and imaging methods, PECM and PEIM provide quantitative electrical current and interfacial impedance information, allowing direct comparison of the data with those obtained by the traditional electrochemical methods, and analysis of the data with the established electrochemical theories. The difference between PECM/PEIM and dark field microscopy is that the former excites SPR on a planar electrode (thin film), and the latter detects light scattering from local surface plasmon resonance (LSPR) in metal nanoparticles. Dark field microscopy is thus particularly suitable for studying metal nanoparticles, while PECM/PEIM image both metallic and dielectric materials on the planar electrode, making it possible to study biological samples, such as cells, bacteria and viruses, in addition to metal nanoparticles. Compared to scanning probe-based electrochemical imaging techniques, PECM and PEIM offer lower spatial resolution, but are less invasive and faster. For a typical electrochemical cell used for PECM and PEIM, subms per image has been achieved. Faster imaging speed is possible by decreasing the size of the electrodes and optimizing the electrolyte resistance drop. High speed imaging capability allows study of fast electrochemical reactions and processes. The plasmonic imaging techniques (PECM and PEIM) described here have limitations and can be further improved in several directions. For example, PECM relies on detecting the polarizability difference between the reactant and product, so its detection limit in terms of current density varies from system to system. For Ru(NH3)63+, the detection limit is on the order ∼0.5 pA/μm2.46 Further improvement of the detection limit requires reduction of noise from different sources. The spatial resolution of PECM/PEIM are limited by optical diffraction, which is on the order of ∼0.2 μm for a high numerical (e.g., 1.49) aperture objective. However, the tail along the propagation direction of the surface plasmonic wave extends over several micrometers, which may be corrected with an imaging correction algorithm. We anticipate that PECM and PEIM help resolve electrochemical properties of nano- and microscaled materials (nanoparticles, nanowires, and nanodroplets97), and image biological samples. This is especially the case when we combine them with other technologies. Currently, building on top of an inverted optical microscope, simultaneous PECM, PEIM, SPR, and bright field optical imaging of the same sample is possible. The optics is also compatible with fluorescence and dark field imaging. Recently, PECM and PEIM have been combined with scanning-probe (micropipet and nanopipet) based electro-

Notes

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. *E-mail: [email protected]. The authors declare no competing financial interest. Biographies Yimin Fang received his B.S. and Ph.D in Chemistry from Fuzhou University, China. Currently he is an associate research professor in the School of Chemistry and Chemical Engineering at Nanjing University (NJU), China. His research focuses on plasmonic imaging of single nanoparticles. Hui Wang received her B.S. in Chemistry, Chemical Engineering and Materials Science from Soochow University, China. Currently she is a Ph.D. student in the School of Chemistry and Chemical Engineering at NJU. Hui Yu received his B.S. and Ph.D in Biomedical Engineering from Zhejiang University, China. Currently he is an assistant research scientist in the Biodesign Center for Bioelectronics and Biosensors at Arizona State University. His research interests include enineering solutions for biomedical applications. Xianwei Liu received his PhD in Chemistry from the University of Science & Technology of China (USTC) in 2011. He became professor at USTC in 2016. His research interests include plasmonic imaging for environment applications. Wei Wang He received his B.S. and Ph.D in Chemistry from USTC. He became professor in Nanjing University in 2013. His research interests mainly focus on single cell, single nanoparticle and single molecule analysis. Hong-Yuan Chen is a professor at NJU. His research interests include electrochemical biosensing, bioelectrochemistry, ultramicroelectrodes, biomolecular-electronic devices, and micrototal analysis systems. Nongjian (NJ) Tao is a professor at NJU and ASU. His current research interests focus on charge transport in single molecules, chemical sensors for mobile health applications, and detection technologies for drug discovery.

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ACKNOWLEDGMENTS

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REFERENCES

Works from the authors’ laboratories were supported by National Natural Science Foundation of China (NSFC, Grant No. 21327008, 21327902, and 21522503), and Natural Science Foundation of Jiangsu Province (BK20150013 and BK20150570).

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