Sonia Sheikh

Label-free detection of HIV-2 antibodies in serum with an ultra-high frequency acoustic wave sensor

Herein is described a label-free immunosensor dedicated to the detection of HIV-2. The biosensor platform is constructed as a mixed self-assembled monolayer-coated quartz wafer onto which HIV-2 immunodominant epitopes are immobilized. The biosensing properties, in terms of specific vs. non-specific antigen-antibody interactions, are evaluated with the electromagnetic piezoelectric acoustic sensor (EMPAS) using equimolar serum solutions of HIV-2 or HIV-1 monoclonal antibodies, respectively. This immunosensor constitutes the first real-world application of the EMPAS technology in the bioanalytical field.

Antifouling Polymer Brushes Displaying Antithrombogenic Surface Properties

The contact of blood with artificial materials generally leads to immediate protein adsorption (fouling), which mediates subsequent biological processes such as platelet adhesion and activation leading to thrombosis. Recent progress in the preparation of surfaces able to prevent protein fouling offers a potential avenue to mitigate this undesirable effect. In the present contribution, we have prepared several types of state-of-the-art antifouling polymer brushes on polycarbonate plastic substrate, and investigated their ability to prevent platelet adhesion and thrombus formation under dynamic flow conditions using human blood. Moreover, we compared the ability of such brushes--grafted on quartz via an adlayer analogous to that used on polycarbonate--to prevent protein adsorption from human blood plasma, assessed for the first time by means of an ultrahigh frequency acoustic wave sensor. Results show that the prevention of such a phenomenon constitutes one promising route toward enhanced resistance to thrombus formation, and suggest that antifouling polymer brushes could be of service in biomedical applications requiring extensive blood-material surface contact.

Acoustic Wave-Based Detection in Bioanalytical Chemistry : Competition for Surface Plasmon Resonance?

Abstract A concise overview of selected literature concerning biosensors based on surface plasmon resonance and acoustic wave technologies is presented. A comparison in terms of their performance and potential advances in the bioanalytical field is discussed. This Mini-Review highlights the generally underrecognized potential of acoustic wave technology, in the field of biosensors relative to plasmon resonance, and focuses on stimulating not only the development of acoustic wave biosensors but also a broader and increased use of them. These sensors are anticipated to play a central role in biodetection in the near future.

New oligoethylene glycol linkers for the surface modification of an ultra-high frequency acoustic wave biosensor

This work describes the application of acoustic wave technology for the real-time and label-free detection of biotin–avidin interactions. Biosensing surfaces are constructed onto unelectroded piezoelectric quartz discs as functionalizable mixed self-assembled monolayers (SAM) produced from previously unreported linker and diluent molecules. Biotinthiol can subsequently be immobilized for detection purposes in a straightforward and coupling-free manner. Specific and non-specific adsorptions of avidin are measured at ultra-high frequencies (1.06 and 0.82 GHz) with an electromagnetic piezoelectric acoustic sensor (EMPAS) using micromolar avidin-spiked buffer solutions. These biosensing surfaces, especially the oligoethylene glycol SAM-based variety, display high specificity for avidin, with moderate to excellent reproducibility. This preliminary work constitutes the first application of SAM chemistry and EMPAS technology in the bioanalytical field.

New Functionalizable Alkyltrichlorosilane Surface Modifiers for Biosensor and Biomedical Applications

We report herein three unprecedented alkyltrichlorosilane surface modifiers bearing pentafluorophenyl ester (PFP), benzothiosulfonate (BTS), or novel β-propiolactone (BPL) functionalizable terminal groups. Evidence is provided that these molecules can be prepared in very high purity (as assessed by NMR) through a last synthetic step of Pt-catalyzed alkene hydrosilylation then directly employed, without further purification, for the surface modification of quartz and medical grade stainless steel. Subsequent on-surface functionalizations with amine and thiol model molecules demonstrate the potential of these molecular adlayers to be important platforms for future applications in the bioanalytical and biomedical fields.

Biocompatibility and antifouling: is there really a link?

Predictably endowing materials with biocompatibility still is a challenge at the beginning of the 21st century. Deleterious biological reactions are the result of cellular processes initiated by surface-activated proteins, which upon adsorption restructured to expose cryptic bioactive sites. One can read however that antifouling – the ability of a surface to prevent proteins from adsorbing and accumulating – would constitute a prerequisite to biomaterial inertia. We argue and propose herein that the key to achieving biocompatibility is not to try and minimize the amount of adsorbed proteins, but the degree of unfolding that relevant ones (i.e., those able to trigger a cellular process) may experience upon co-adsorption with other, bystander proteins.

Prevention of thrombogenesis from whole human blood on plastic polymer by ultrathin monoethylene glycol silane adlayer.

In contemporary society, a large percentage of medical equipment coming in contact with blood is manufactured from plastic polymers. Unfortunately, exposure may result in undesirable protein-material interactions that can potentially trigger deleterious biological processes such as thrombosis. To address this problem, we have developed an ultrathin antithrombogenic coating based on monoethylene glycol silane surface chemistry. The strategy is exemplified with polycarbonate--a plastic polymer increasingly employed in the biomedical industry. The various straightforward steps of surface modification were characterized with X-ray photoelectron spectroscopy supplemented by contact angle goniometry. Antithrombogenicity was assessed after 5 min exposure to whole human blood dispensed at a shear rate of 1000 s(-1). Remarkably, platelet adhesion, aggregation, and thrombus formation on the coated surface was greatly inhibited (>97% decrease in surface coverage) compared to the bare substrate and, most importantly, nearly nonexistent.

On the hydration of subnanometric antifouling organosilane adlayers: a molecular dynamics simulation.

The connection between antifouling and surface hydration is a fascinating but daunting question to answer. Herein, we use molecular dynamics (MD) computer simulations to gain further insight into the role of surface functionalities in the molecular-level structuration of water (surface kosmotropicity)--within and atop subnanometric organosilane adlayers that were shown in previous experimental work to display varied antifouling behavior. Our simulations support the hypothesized intimate link between surface hydration and antifouling, in particular the importance of both internal and interfacial hydrophilicity and kosmotropicity. The antifouling mechanism is also discussed in terms of surface dehydration energy and water dynamicity (lability and mobility), notably the crucial requirement for clustered water molecules to remain tightly bound for extensive periods of time--i.e. exhibit slow exchange dynamics. A substrate effect on surface hydration, which would also participate in endowing antifouling adlayers with hydrogel-like characteristics, is also proposed. In contrast, the role of adlayer flexibility, if any, is assigned a secondary role in these ultrathin structures made of short building blocks. The conclusions from this work are well in line with those previously drawn in the literature.

Probing the hydration of ultrathin antifouling organosilane adlayers using neutron reflectometry.

Neutron reflectometry data and modeling support the existence of a relatively thick, continuous phase of water stemming from within an antifouling monoethylene glycol silane adlayer prepared on oxidized silicon wafers. In contrast, this physically distinct (from bulk) interphase is much thinner and only interfacial in nature for the less effective adlayer lacking internal ether oxygen atoms. These results provide further insight into the link between antifouling and surface hydration.

Low-fouling SPR detection of lysozyme and its aggregates

Protein aggregates adsorb to material surfaces in a different manner than protein monomers and pose additional challenges for biosensor development with regard to non-specific adsorption (NSA). In this context, we describe herein the performance of a new antifouling thiol in a sensor coating resistant to NSA from lysozyme monomers and aggregates. Coatings were prepared as mixed self-assembling monolayers (SAMs) using a long polyethylene glycol carboxyl-terminated thiol (“PEG-COOH”) for the first time in conjunction with a shorter monoethylene glycol hydroxyl-terminated diluent thiol (“MEG-OH”). SAMs and their antifouling properties were characterized by a variety of surface analysis techniques. A key result was that the cleaning procedure drastically affects the antifouling properties of resulting MEG-OH based SAMs. Mixed PEG-COOH/MEG-OH SAMs formed on borohydride cleaned interfaces are able to reduce lysozyme NSA by >90% compared to bare gold; a remarkable performance also displayed for oligomers regardless of their stage of aggregation. Gratifyingly, subsequent SAM functionalisation with an anchoring layer of neutravidin for the preparation of a lysozyme sensor did not significantly alter the antifouling properties of the resulting assembly. The limit of detection for monomeric lysozyme by surface plasmon resonance was 0.3 μg mL−1 with a dynamic range of 3–50 μg mL−1 (R2 = 0.9993). The sensitivity of the technique for the aggregated lysozyme was almost two times higher than that for the protein monomer.