Functionalized Self-Assembled Monolayers: Versatile Strategies to Combat Bacterial Biofilm Formation.

Bacterial infections due to biofilms account for up to 80% of bacterial infections in humans. With the increased use of antibiotic treatments, indwelling medical devices, disinfectants, and longer hospital stays, antibiotic resistant infections are sharply increasing. Annual deaths are predicted to outpace cancer and diabetes combined by 2050. In the past two decades, both chemical and physical strategies have arisen to combat biofilm formation on surfaces. One such promising chemical strategy is the formation of a self-assembled monolayer (SAM), due to its small layer thickness, strong covalent bonds, typically facile synthesis, and versatility. With the goal of combating biofilm formation, the SAM could be used to tether an antibacterial agent such as a small-molecule antibiotic, nanoparticle, peptide, or polymer to the surface, and limit the agent's release into its environment. This review focuses on the use of SAMs to inhibit biofilm formation, both on their own and by covalent grafting of a biocidal agent, with the potential to be used in indwelling medical devices. We conclude with our perspectives on ongoing challenges and future directions for this field.

A Supramolecular Approach to Antimicrobial Surfaces.

In this paper, we report on the preparation of Imidazole-functionalized glass surfaces, demonstrating the ability of a dinuclear Cu(II) complex of a macrocyclic ligand to give a "cascade" interaction with the deprotonated forms of grafted imidazole moieties. In this way, we realized a prototypal example of an antimicrobial surface based on a supramolecular approach, obtaining a neat microbicidal effect using low amounts of the described copper complex.

Towards an Electrochemical Immunosensor for the Detection of Antibodies against SARS-CoV-2 Spike Protein

Herein we report the electrochemical system for the detection of specific antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in blood serum patient samples after coronavirus disease 2019 (COVID-19). For this purpose, the recombinant SARS-CoV-2 spike protein (SCoV2-rS) was covalently immobilised on the surface of the gold electrode pre-modified with mixed self-assembled monolayer (SAMmix) consisting of 11-mercaptoundecanoic acid and 6-mercapto-1-hexanol. The affinity interaction of SCoV2-rS with specific antibodies against this protein (anti-rS) was detected using two electrochemical methods: cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The anti-rS was detected with a detection limit of 2.53 nM and 1.99 nM using CV and EIS methods, respectively. The developed electrochemical immunosensor is suitable for the confirmation of COVID-19 infection or immune response in humans after vaccination.

Morphological and Mechanical Characterization of DNA SAMs Combining Nanolithography with AFM and Optical Methods.

The morphological and mechanical properties of thiolated ssDNA films self-assembled at different ionic strength on flat gold surfaces have been investigated using Atomic Force Microscopy (AFM). AFM nanoshaving experiments, performed in hard tapping mode, allowed selectively removing molecules from micro-sized regions. To image the shaved areas, in addition to the soft contact mode, we explored the use of the Quantitative Imaging (QI) mode. QI is a less perturbative imaging mode that allows obtaining quantitative information on both sample topography and mechanical properties. AFM analysis showed that DNA SAMs assembled at high ionic strength are thicker and less deformable than films prepared at low ionic strength. In the case of thicker films, the difference between film and substrate Young's moduli could be assessed from the analysis of QI data. The AFM finding of thicker and denser films was confirmed by X-Ray Photoelectron Spectroscopy (XPS) and Spectroscopic Ellipsometry (SE) analysis. SE data allowed detecting the DNA UV absorption on dense monomolecular films. Moreover, feeding the SE analysis with the thickness data obtained by AFM, we could estimate the refractive index of dense DNA films.

Ultrasensitive and Label-Free Detection of the Measles Virus Using an N-Heterocyclic Carbene-Based Electrochemical Biosensor.

With the current intense need for rapid and accurate detection of viruses due to COVID-19, we report on a platform technology that is well suited for this purpose, using intact measles virus for a demonstration. Cases of infection due to the measles virus are rapidly increasing, yet current diagnostic tools used to monitor for the virus rely on slow (>1 h) technologies. Here, we demonstrate the first biosensor capable of detecting the measles virus in minutes with no preprocessing steps. The key sensing element is an electrode coated with a self-assembled monolayer containing the measles antibody, immobilized through an N-heterocyclic carbene (NHC). The intact virus is detected by changes in resistance, giving a linear response to 10-100 µg/mL of the intact measles virus without the need to label or process the sample. The limit of detection is 6 µg/mL, which is at the lower limit of concentrations that can cause infections in primates. The NHC-based biosensors are shown to be superior to thiol-based systems, producing an approximately 10× larger response and significantly greater stability toward repeated measurements and long-term storage. This NHC-based biosensor thus represents an important development for both the rapid detection of the measles virus and as a platform technology for the detection of other biological targets of interest.

Design of engineered surfaces for prospective detection of SARS-CoV-2 using quartz crystal microbalance-based techniques.

INTRODUCTION: Rapid transmission of the severe acute respiratory syndrome coronavirus 2 has affected the whole world and forced it to a halt (lockdown). A fast and label-free detection method for the novel coronavirus needs to be developed along with the existing enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR)-based methods. AREAS COVERED: In this report, biophysical aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein are outlined based on its recent reported electron microscopy structure. Protein binding sites are analyzed theoretically, which consisted of hydrophobic and positive charged amino acid residues. Different strategies to form mixed self-assembled monolayers (SAMs) of hydrophobic (CH3) and negatively charged (COOH) groups are discussed to be used for the specific and strong interactions with spike protein. Bio-interfacial interactions between the spike protein and device (sensor) surface and its implications toward designing suitable engineered surfaces are summarized. EXPERT OPINION: Implementation of the engineered surfaces in quartz crystal microbalance (QCM)-based detection techniques for the diagnosis of the novel coronavirus from oral swab samples is highlighted. The proposed strategy can be explored for the label-free and real-time detection with sensitivity up to ng level. These engineered surfaces can be reused after desorption.