Bare Gold Surface Research Articles

Zwitter-repel: An anti-fouling coating promoting electrochemical biosensing in biological fluids

Most electrochemical biosensors require sample processing to reduce biofouling induced by the complex composition of biological samples that typically causes a decrease in the target-to-blank signal. Herein, we report a zwitterionic copolymer bearing sulfobetaine, carboxylic, aldehyde, and thiol groups as a thin (∼16 nm) anti-fouling coating for electrochemical biosensing platforms. The resulting polymer-coated electrodes reduced protein adsorption by ∼ 67 % compared to the bare-gold surface when incubated with radiolabeled human serum albumin (HSA) protein-spiked human plasma, while cyclic voltammetry yielded a 5 % increase in anodic current signal after incubation in 1 % HSA for 1 h compared to the 83 % decrease in anodic current observed with bare gold electrodes. The polymer-coated electrode facilitated the detection of redox-labeled DNA in buffer, as well as in unprocessed and undiluted plasma with detection limits of 23 nM and 21 nM, respectively; detection of 104 cp mL−1 lentivirus pseudotyped with the Omicron spike protein of SARS-CoV-2 in unfiltered 50 % saliva was also achieved within 5 min with improved target-to-blank ratios and reproducibility relative to the well-established PEG-based biosensing platform for detecting COVID-19. On this basis, the Zwitter-repel coating offers potential to sensitively detect other disease biomarkers/analytes while eliminating or reducing the need for sample pre-processing and/or the use of additional backfilling/blocking agents.

Reliable detection of malachite green by self-assembled SERS substrates based on gold–silicon heterogeneous nano pineapple structures

Morphology regulation of heterodimer nanoparticles and the use of their asymmetric features for further practical applications are crucial because of the rich optical properties and various combinations of heterodimers. This work used silicon to asymmetrically wrap half of a gold sphere and grew gold branches on the bare gold surface to form heterogeneous nano pineapples (NPPs) which can effectively improve Surface-enhanced Raman scattering (SERS) properties through chemical enhancement and lightning-rod effect respectively. The asymmetric structures of NPPs enabled them to self-assemble into the monolayer membrane with consistent branch orientation. The prepared substrate had high homogeneity and better SERS ability than disorganized substrates, and achieved reliable detection of malachite green (MG) in clams with a detection limit of 7.8 × 10−11 M. This work provided a guide to further revise the morphology of heterodimers and a new idea for the use of asymmetric dimers for practically photochemical and biomedical sensing.

Binding energies of ethanol and ethylamine on interstellar water ices: synergy between theory and experiments.

Experimental and computational chemistry are two disciplines used to conduct research in astrochemistry, providing essential reference data for both astronomical observations and modeling. These approaches not only mutually support each other, but also serve as complementary tools to overcome their respective limitations. Leveraging on such synergy, we characterized the binding energies (BEs) of ethanol (CH3CH2OH) and ethylamine (CH3CH2NH2), two interstellar complex organic molecules (iCOMs), on crystalline and amorphous water ices through density functional theory (DFT) calculations and temperature-programmed desorption (TPD) experiments. Experimentally, CH3CH2OH and CH3CH2NH2 behave similarly, in which desorption temperatures are higher on the water ices than on a bare gold surface. Computed cohesive energies of pure ethanol and ethylamine bulk structures allow describing of the BEs of the pure species deposited on the gold surface, as extracted from the TPD curve analyses. The BEs of submonolayer coverages of CH3CH2OH and CH3CH2NH2 on the water ices cannot be directly extracted from TPD due to their co-desorption with water, but they are computed through DFT calculations, and found to be greater than the cohesive energy of water. The behaviour of CH3CH2OH and CH3CH2NH2 is different when depositing adsorbate multilayers on the amorphous ice, in that, according to their computed cohesive energies, ethylamine layers present weaker interactions compared to ethanol and water. Finally, from the computed BEs of ethanol, ethylamine and water, we can infer that the snow-lines of these three species in protoplanetary disks will be situated at different distances from the central star. It appears that a fraction of ethanol and ethylamine is already frozen on the grains in the water snow-lines, causing their incorporation in water-rich planetesimals.

Antifouling Properties of Poly(2-Oxazoline)s and Poly(2-Oxazine)s: Direct Comparison of Polymer-Coated Surfaces with the Same Coating Parameters.

This study presents a systematic comparison of the antifouling properties of water-soluble poly(2-oxazoline) (PAOx) and poly(2-oxazine) (PAOzi) brushes grafted to gold surfaces. PAOx and PAOzi are emerging polymer classes in biomedical sciences and are being considered superior alternatives to widely used polyethylene glycol (PEG). Four different polymers, poly(2-methyl-2-oxazoline) (PMeOx), poly(2-ethyl-2-oxazoline) (PEtOx), poly(2-methyl-2-oxazine) (PMeOzi), and poly(2-ethyl-2-oxazine) (PEtOzi), each of them in three different chain lengths, are synthesized and characterized for their antifouling properties. Results show that all polymer-modified surfaces display better antifouling properties than bare gold surfaces as well as analogous PEG coatings. The antifouling properties increase in the following order: PEtOx<PMeOx≈ PMeOzi<PEtOzi. The study suggests that the resistance to protein fouling derives from both surface hydrophilicity and the molecular structural flexibility of the polymer brushes. PEtOzi brushes with moderate hydrophilicity show the best antifouling performance, possibly due to their highest chain flexibility. Overall, the research contributes to the understanding of antifouling properties in PAOx and PAOzi polymers, with potential applications in various biomaterials.

MoS2-Nanoflower and Nanodiamond Co-Engineered Surface Plasmon Resonance for Biosensing

Surface plasmon resonance (SPR) based sensors play an important role in the biological and medical fields, and improving the sensitivity is a goal that has always been pursued. In this paper, a sensitivity enhancement scheme jointly employing MoS2 nanoflower (MNF) and nanodiamond (ND) to co-engineer the plasmonic surface was proposed and demonstrated. The scheme could be easily implemented via physically depositing MNF and ND overlayers on the gold surface of an SPR chip, and the overlayer could be flexibly adjusted by controlling the deposition times, thus approaching the optimal performance. The bulk RI sensitivity was enhanced from 9682 to 12,219 nm/RIU under the optimal condition that successively deposited MNF and ND 1 and 2 times. The proposed scheme was proved in an IgG immunoassay, where the sensitivity was twice enhanced compared to the traditional bare gold surface. Characterization and simulation results revealed that the improvement arose from the enhanced sensing field and increased antibody loading via the deposited MNF and ND overlayer. At the same time, the versatile surface property of NDs allowed a specifically-functionalized sensor using the standard method compatible with a gold surface. Besides, the application for pseudorabies virus detection in serum solution was also demonstrated.

Novel functional monomer for the electrochemical synthesis of highly affine epitope‐imprinted polymers

AbstractTo address the lack of functional monomer diversity for the electrosynthesis of protein‐selective molecularly imprinted polymers (MIPs), we introduce a new concept able to lead to a new class of functional monomers. This is based on conjugating an electropolymerizable monomer unit (umbelliferone) to an amino acid for closer mimicking of protein‐based natural affinity ligands such as antibodies. As the first representative of this class of monomers an aspartate‐umbelliferone (Asp‐UMB) conjugate was synthesized and here we provide the proof for its suitability to generate highly affine MIPs for proteins by epitope imprinting. As model we used a heptapeptide (GFNCYFP) stemming from the receptor binding domain (RBD) of the SARS‐CoV‐2 spike protein to generate epitope‐imprinted polymers able to recognize the parent RBD protein. For rapid optimization and assessment of the binding kinetics we prepared MIP microarrays on surface plasmon resonance imaging (SPRi) chips. First the peptides were microspotted on the bare gold surface of the chips followed by the electropolymerization of Asp‐UMB. This resulted in ca. 2 nm thick, highly uniform, and electrically insulating polymer film, well suited both for hierarchical epitope imprinting and SPRi read‐out. Taking advantage also of the on‐chip optimization enabled by the microarray format the increased functional diversity of the new monomer resulted in highly affine MIPs with equilibrium dissociation constants in the lower picomolar range.

Graphene on Nanoscale-Thick Au Films: Implications for Anticorrosion in Smart Wearable Electronics

Gold is normally considered inert to chemical reaction. Nevertheless, as a common electrode material, it would suffer from corrosion when exposed to certain solutions such as sweat and body fluids. Here, we report low-temperature plasma-enhanced chemical vapor deposition (PECVD) of graphene on gold and demonstrate its feasibility for anticorrosion application. The effects of hydrogen-to-methane ratio and the underlying gold substrate on the graphene growth are investigated, and the growth mechanism of PECVD graphene on gold is proposed. When immersed in an oxygenated saline solution, the PECVD-grown graphene-covered gold surface is found to remain intact after an acceleration soaking test at 90 °C for 24 h, which is in contrast to the degradation of bare gold surface subject to the same test. Our findings suggest that consumer/medical wearables and implantable devices with exposed gold can benefit from the protection of a direct, low-temperature PECVD-grown graphene layer for anticorrosion, thereby prolonging the efficacy and reliability of gold electrode-based biosensors.

Between Two Walls: Modeling the Adsorption Behavior of β-Glucosidase A on Bare and SAM-Functionalized Gold Surfaces.

The efficient immobilization of enzymes on surfaces remains a complex but central issue in the biomaterials field, which requires us to understand this process at the atomic level. Using a multiscale approach combining all-atom molecular dynamics and coarse-grain Brownian dynamics simulations, we investigated the adsorption behavior of β-glucosidase A (βGA) on bare and self-assembled monolayer (SAM)-functionalized gold surfaces. We monitored the enzyme position and orientation during the molecular dynamics (MD) trajectories and measured the contacts it forms with both surfaces. While the adsorption process has little impact on the protein conformation, it can nonetheless perturb its mechanical properties and catalytic activity. Our results show that compared to the SAM-functionalized surface, the adsorption of βGA on bare gold is more stable, but less specific, and more likely to disrupt the enzyme's function. This observation emphasizes the fact that the structural organization of proteins at the solid interface is a key point when designing devices based on enzyme immobilization, as one must find an acceptable stability-activity trade-off.

Ultrasensitive Optical Temperature Transducers Based on Surface Plasmon Resonance Enhanced Composited Goos-Hänchen and Imbert-Fedorov Shifts

The spatial and angular Goos-Hänchen and Imbert-Fedorov shifts occur simultaneously for the light beam reflected from a lossy surface (e.g., metal surface). The mixture of spatial and angular Goos-Hänchen (Imbert-Fedorov) shifts, referred to as composited Goos-Hänchen (Imbert-Fedorov) shift, has been experimentally confirmed in recent years. The temperature-dependent composite Goos-Hänchen and Imbert-Fedorov shifts for a light beam reflected from the prism-gold interface in the Kretschmann-Raether configuration are theoretically investigated. The spatial and angular Goos-Hänchen and Imbert-Fedorov shitfs of p-polarized incident light are significantly enhanced around the resonant angle with the generation of surface plasmon resonance. The ultrahigh temperature sensitivities of 0.79 cm/K and 188 μm/K are obtained with the composite Goos-Hänchen and Imbert-Fedorov shift, respectively, which are about 5 orders higher than those obtained with a bare gold surface. The ultrahigh temperature sensitivity is mostly contributed by the angular shift effect. Our results demonstrated the importance of angular shift effect in achieving an ultrahigh sensitivity. This work can serve as a guidance for the design of temperature sensor, chemical sensor and biosensor based on composite Goos-Hänchen and Imbert-Fedorov shifts.

Chiral Recognition on Bare Gold Surfaces by Quartz Crystal Microbalance.

Quartz crystal microbalance (QCM) is one of the powerful tools for the studies of molecular recognition and chiral discrimination. Its efficiency mainly relies on the design of the functional sensitive layer on the electrode surface. However, the organic sensitive layer may easily cause dissipation of oscillation or detachment and weaken the signal transfer during the molecular recognition processes. In this work, we reveal for the first time that the bare metal surface without the organic selector layer has the capability for chiral recognition in the QCM system. During the adsorption of various chiral amino acids, relatively higher selectivity of D-enantiomers on gold (Au) surface was shown by the QCM detection. Based on analyses of the surface crystalline structure and density functional theory calculations, we demonstrate that the chiral nature of Au surface plays an important role in the selective binding of specific D-amino acids. These results may open new insights on chiral detection by QCM system. It will also promote the construction of novel chiral sensing systems with both efficient detection and separation capability.

Chiral Recognition on Bare Gold Surfaces by Quartz Crystal Microbalance

AbstractQuartz crystal microbalance (QCM) is one of the powerful tools for the studies of molecular recognition and chiral discrimination. Its efficiency mainly relies on the design of the functional sensitive layer on the electrode surface. However, the organic sensitive layer may easily cause dissipation of oscillation or detachment and weaken the signal transfer during the molecular recognition processes. In this work, we reveal for the first time that the bare metal surface without the organic selector layer has the capability for chiral recognition in the QCM system. During the adsorption of various chiral amino acids, relatively higher selectivity of D‐enantiomers on gold (Au) surface was shown by the QCM detection. Based on analyses of the surface crystalline structure and density functional theory calculations, we demonstrate that the chiral nature of Au surface plays an important role in the selective binding of specific D‐amino acids. These results may open new insights on chiral detection by QCM system. It will also promote the construction of novel chiral sensing systems with both efficient detection and separation capability.

Amplification-free Detection of Cytomegalovirus miRNA Using a Modification-free Surface Plasmon Resonance Biosensor.

Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide; congenital CMV may lead to significant mortality, morbidity, or long-term sequelae, such as sensorineural hearing loss. The current study presents a newly designed surface plasmon resonance (SPR) biosensor for CMV-specific microRNAs that does not involve extra care for receptor immobilization or treatment to prevent fouling on bare gold surfaces. The modification-free approach, which utilizes a poly-adenine [poly(A)]-Au interaction, exhibited a high affinity that was comparable to that of the gold-sulfur (Au-S) interaction. In addition, magnetic nanoparticles (MNPs) were used to separate the analyte from complex sample matrixes that significantly reduced nonspecific adsorption. Moreover, the MNPs also played an important role in SPR signal amplification due to the binding-induced change in the refractive index. Our SPR biosensing platform was used successfully for the multi-detection of the microRNAs, UL22A-5p, and UL112-3p, which were associated with CMV. Our SPR biosensor offered the detection limits of 108 fM and 24 fM for UL22A-5p and UL112-3p, respectively, with an R2 of 0.9661 and 0.9985, respectively. The precision of this biosensor has an acceptable CV (coefficient of variation) value of <10%. In addition, our sensor is capable of discriminating between serum samples collected from healthy and CMV-infected newborns. Taken together, we believe that our newly developed SPR biosensing platform is a promising alternative for the diagnosis of CMV-specific microRNA in clinical settings, and its application for the detection of other miRNAs may be extended further.

Detection of amoxicillin residues in egg extract with a molecularly imprinted polymer on gold microchip using surface plasmon resonance and quartz crystal microbalance methods.

In this study, surface plasmon resonance (SPR) and quartz crystal microbalance (QCM) sensors were prepared for the detection of amoxicillin from the commercial and local chicken eggs by using molecular imprinting technique. Amoxicillin imprinted poly(hydroxyethyl methacrylate-methacrylic acid) polymeric film was synthesized onto the surface of the SPR and QCM chips by ultra violet polymerization to determine lower concentrations of amoxicillin. Ellipsometry, contact angle analysis, and atomic force microscopy measurements were used for the surface morphology of the polymeric film layer. The ellipsometric thickness of AMOX imprinted and nonimprinted SPR and QCM chip surfaces were measured as 35 ± 0.9nm,32.89 ± 1.9nm,30 ± 0.6nm, and 28 ± 0.22nm,respectively. Contact angles of bare gold surfaces, AMOX imprinted SPR and QCM chip surfaces were measured to be as 82.3° ± 0.15, 79.2° ± 0.14, 75.01° ± 1.07, and 69.11° ± 0.89, respectively. The range of linearity was measured as 0.1 to 10ng/mL for amoxicillin imprinted SPR and QCM sensors. The maximum residue limit of AMOX in eggs is at 10µg/kg in accordance with the "Positive List System for Agricultural Chemical Residues in Foods." The response time for the test, including adsorption, desorption, and regeneration, was approximately 45min. The limit of detections for SPR and QCM sensors were found to be 0.0005 and 0.0023ng/mL, respectively. The reusabilities of amoxicillin imprinted SPR and QCM sensors were observed by the equilibration-binding-regeneration. Validation studies of the AMOX imprinted SPR and QCM sensors were performed by liquid chromatography-tandem mass spectrometry.

Selective Promotion of Adhesion of Shewanella oneidensis on Mannose-Decorated Glycopolymer Surfaces.

Using glycopolymer surfaces, we have stimulated Shewanella oneidensis bacterial colonization and induced where the bacteria attach on a molecular pattern. When adherent bacteria were rinsed with methyl α-d-mannopyranoside, the glycopolymer-functionalized surfaces retained more cells than self-assembled monolayers terminated by a single mannose unit. These results suggest that the three-dimensional multivalency of the glycopolymers both promotes and retains bacterial attachment. When the methyl α-d-mannopyranoside competitor was codeposited with the cell culture, however, the mannose-based polymer was not significantly different from bare gold surfaces. The necessity for equilibration between methyl α-d-mannopyranoside and the cell culture to remove the enhancement suggests that the retention of cells on glycopolymer surfaces is kinetically controlled and is not a thermodynamic result of the cluster glycoside effect. The MshA lectin appears to facilitate the improved adhesion observed. Our findings that the surfaces studied here can induce stable initial attachment and influence the ratio of bacterial strains on the surface may be applied to harness useful microbial communities.

Electrochemical Characterization of Redox Probes at Gold Screen‐Printed Electrodes: Efforts towards Signal Stability

AbstractIn this work, three universally used redox probes in amperometric biosensing devices, [Fe(CN)6]3−/[Fe(CN)6]4−, Ru[(NH3)6]3+, and ferrocenedimethanol (FDM), were selected to evaluate the stability of electrochemical signals provide by the reporting systems. Studies were carried out at disposable gold screen‐printed electrode (AuSPE) biosensing platforms, commonly used for screening chemical and biological relevant biomolecules. Firstly, electrochemical combined‐surface plasmon resonance (eSPR) studies were performed to evaluated adsorption reversibility and/or formation of redox probe complexes at the bare gold surface when routinely used electrochemical techniques, namely cyclic voltammetry (CV) and square‐wave voltammetry (SWV), are recorded. Then, the results obtained were compared with those obtained at the AuSPE under the same electrochemical conditions. Based on our findings, best experimental conditions, including the type of electrochemical technique used, are speculated for each reporting system in order to improve the analytical signal stability. Finally, a methodology based on SWV technique was applied to modified electrodes to provide a simple and easy tool to ensure diffusion controlled permeability of probes thorough the films to electrode surface.

Preparing DNA SAM Electrochemical Sensors Using Potential Assisted Deposition Methods. Controlling the Coverage and Local Organization of the DNA in the SAM.

Typically, DNA SAMs used for electrochemical based sensing are prepared without controlling the gold electrode potential[1]. Applying a potential during DNA deposition enables control over the coverage and DNA organization[2-4]. These characteristics are determined by the composition of the immobilization buffer, the immersion time, the DNA concentration, the extent of backfilling with a small alkylthiol and whether deposition occurs on a bare or alkythiol coverage gold surface[3-4]. Few studies have explored the influence of the underlying surface crystallography. Here, we show the possibilities of using electrochemical potential control to manipulate the characteristics of the DNA SAM. Moreover, the use of a single crystal gold bead electrode, coupled with the use of a fluorophore tagged DNA and fluorescence microscopy, enables examination of the influence of the underlying surface crystallography on the DNA SAM prepared. Various constant potentials were used as well as using a square-wave potential perturbation during deposition. There are significant differences in the DNA SAM produced under these conditions. In some cases, the DNA coverage was low on the <111> surfaces, higher on more open or atomically rough regions. In other cases, the coverage was higher on the <100> surfaces as compared to the other regions. The use of constant positive or negative potentials (vs SCE) resulted in significant differences in the relative coverages among regions of different atomic arrangements (Fig 1). In addition, a significant difference was observed between immobilization buffers that contain Cl and those that are Cl free. Also, the use of constant or square-wave potential perturbations resulted in significantly different local organizations of DNA in the SAM. Examples of these types of DNA SAM surfaces will be presented with some conclusions on the implications for use on polycrystalline planar gold surfaces.

Supramolecular Presentation of Hyaluronan onto Model Surfaces for Studying the Behavior of Cancer Stem Cells.

The supramolecular presentation of extracellular matrix components on surfaces provides a platform for the investigation and control of cell behavior. Hyaluronan (HA) is one of the main components of the extracellular environment and has been shown to play an important role in different cancers and their progression. However, current methods of HA immobilization often require its chemical modification. Herein, a peptide-based self-assembled monolayer (SAM) is used as an anchor to immobilize unmodified HA on a bare gold surface, as demonstrated by the quartz crystal microbalance with dissipation monitoring. Peptide-HA surfaces show increased roughness and greater hydrophobicity when compared to poly-D-lysine/HA surfaces, as measured by atomic force microscopy and water contact angle, respectively. Additionally, the peptide SAM can be micro-contact printed and used to restrict the presentation of HA to specific regions, thereby creating HA patterned surfaces to examine cell behavior. When used for cell culture, these surfaces result in altered adhesion and migration of LUC4 head and neck squamous cell carcinoma cells. These biomimetic surfaces can provide insights into the role of HA in cancer and other diseases and be used as a platform for the development of cell sorting devices.

Synthesis of Fe₃C@C from Pyrolysis of Fe₃O₄-Lignin Clusters and Its Application for Quick and Sensitive Detection of PrPSc through a Sandwich SPR Detection Assay.

The prion protein (PrPSc) has drawn widespread attention due to its pathological potential to cause prion diseases. Herein, we successfully synthesized Fe3C@C by carbonizing Fe3O4-lignin clusters, which were prepared through a facile hydrogen bonding interaction between ≡Fe-OH and hydroxyl groups of lignin. Our in-depth investigation confirmed that the composites were Fe3C@C core/shell particles. We constructed a novel sandwich surface plasmon resonance (SPR) detection assay for sensitive PrPSc detection, utilizing bare gold surface and aptamer-modified Fe3C@C (Fe3C@C-aptamer). Due to the highly specific affinity of Fe3C@C-aptamer towards PrPSc, the sandwich type SPR sensor exhibited excellent analytical performance towards the discrimination and quantitation of PrPSc. A good linear relationship was obtained between the SPR responses and the logarithm of PrPSc concentrations over a range of 0.1–200 ng/mL. The detection sensitivity for PrPSc was improved by ~10 fold compared with the SPR direct detection format. The required detection time was only 20 min. The specificity of the present biosensor was also confirmed by PrPC and other reagents as controls. This proposed approach could also be used to isolate and detect other highly pathogenic biomolecules with similar structural characteristics by altering the corresponding aptamer in the Fe3C@C conjugates.

Rapid and on-site electrochemical detection of bisphenol A and arsenic indrinking water using a novel electrode array

The paper describes a novel dip-and-gauge hand-held sensor device for the rapid, cost-effective, and on-site detection of bisphenol A and arsenic in drinking water samples. Different working electrode diameters ranging from 1.5 mm to 4 mm were designed and fabricated to construct a new electrochemical biosensor. The sensor was employed for the chronoamperometric detection of bisphenol A and voltammetric determination of arsenic in drinking water samples. Bisphenol A measurements resulted in a detection limit of 10 ng mL$^{-1}$ with a linear range of 0-4000 ng mL$^{-1}$. Baby products and bottles have to be completely free of bisphenol and hence a liquid-phase microextraction method has been developed to reduce the detection limit further to 0.6 ng mL$^{-1}$. Arsenic detection was investigated in the concentration range of 0.4-250 ng mL$^{-1}$ with a detection limit of 1.9 ng mL$^{-1}$. The current study showed that the designed electrode array allows low detection limits (below threshold levels), although a bare gold surface is used for the study. Hence, together with a hand-held sensor device that works by simply dipping the sensor chip into a water container, this cost effective system has the potential to be used either by household consumers or for on-site inspection purposes.

Analysis of Nucleobase Adsorption Onto Bare Gold Surfaces Using Electrochemical Sensing

Affinity interactions between strands of oligonucleotides to bare gold surfaces has been previously established using infrared-based analysis techniques (Kimura-suda et al., 2003). The gradient of affinity interactions has been the basis of detecting methylation in a nucleotide sequence. For example, eMethylsorb detects the percent of DNA methylation using differential pulse voltammetry to determine amount of adsorbed methylated DNA on gold surfaces compared to nonmethylated sequences (Koo et al., 2014). Sensing DNA methylation electrochemically can lead to the development of a point-of-care sensor to diagnose diseases (e.g. cancer, psychiatric disorders) linked to DNA methylation. A sensor that could evaluate global methylation levels without the need of a more expensive genetic sequencing method could be very useful for initial detection. While differential pulse voltammetry is a useful technique, we hypothesize that electrochemical impedance spectroscopy can provide greater sensitivity. In addition, we are interested in the effect of chain-length on the ability to look at affinity of DNA via electrochemical methods. While electrochemical studies have previously analyzed longer methylated sequences (Koo et al., 2015), we will report on individual nucleic acid bases and smaller repetitive oligonucleotide sequences. Although there is value at looking in longer sequence adsorption, it requires the isolation of a specific sequence, leading to a larger required sample size, higher cost, and more time. A budding technique in the epigenetic field is examining global levels of methylation which looks at the overall DNA instead of a certain section (Kurdyukov and Bullock, 2016). Individual nucleobases have been characterized through modeling to predict gold interactions, but the affinity interactions between individual nucleobases and gold surfaces have never been characterized electrochemically (Piana and Bilic, 2006). We first propose to investigate the measurement of individual nucleic acid bases before investigating the global DNA makeup. The fundamental aspect of this approach is to understand the resolution and reproducibility of electrochemical characterization of nucleobases. We will discuss the effect of the solvent used to dissolve nucleobases, oligonucleotide length, and detection technique (e.g. electrochemical impedance spectroscopy, cyclic voltammetry) on the ability to electrochemically distinguish nucleobases. We will conclude with a set of electrochemical conditions to optimally deduce nucleobase absorption on gold surfaces.