Review on carbon-derived, solid-state, micro and nano sensors for electrochemical sensing applications

The aim of this review is to summarize the most relevant contributions in the development of electrochemical sensors based on carbon materials in the recent years. There have been increasing numbers of reports on the first application of carbon derived materials for the preparation of an electrochemical sensor. These include carbon nanotubes, diamond like carbon films and diamond film-based sensors demonstrating that the particular structure of these carbon material and their unique properties make them a very attractive material for the design of electrochemical biosensors and gas sensors. Carbon nanotubes (CNT) have become one of the most extensively studied nanostructures because of their unique properties. CNT can enhance the electrochemical reactivity of important biomolecules and can promote the electron-transfer reactions of proteins (including those where the redox center is embedded deep within the glycoprotein shell). In addition to enhanced electrochemical reactivity, CNT-modified electrodes have been shown useful to be coated with biomolecules (e.g., nucleic acids) and to alleviate surface fouling effects (such as those involved in the NADH oxidation process). The remarkable sensitivity of CNT conductivity with the surface adsorbates permits the use of CNT as highly sensitive nanoscale sensors. These properties make CNT extremely attractive for a wide range of electrochemical sensors ranging from amperometric enzyme electrodes to DNA hybridization biosensors. Recently, a CNT sensor based fast diagnosis method using non-treated blood assay has been developed for specific detection of hepatitis B virus (HBV) (human liver diseases, such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma caused by hepatitis B virus). The linear detection limits for HBV plasma is in the range 0.5–3.0 μL−1 and for anti- HBVs 0.035–0.242 mg/mL in a 0.1 M NH4H2PO4 electrolyte solution. These detection limits enables early detection of HBV infection in suspected serum samples. Therefore, non-treated blood serum can be directly applied for real-time sensitive detection in medical diagnosis as well as in direct in vivo monitoring. Synthetic diamond has been recognized as an extremely attractive material for both (bio-) chemical sensing and as an interface to biological systems. Synthetic diamond have outstanding electrochemical properties, superior chemical inertness and biocompatibility. Recent advances in the synthesis of highly conducting nanocrystalline-diamond thin films and nano wires have lead to an entirely new class of electrochemical biosensors and bio-inorganic interfaces. In addition, it also combines with development of new chemical approaches to covalently attach biomolecules on the diamond surface also contributed to the advancement of diamond-based biosensors. The feasibility of a capacitive field-effect EDIS (electrolyte-diamond-insulatorsemiconductor) platform for multi-parameter sensing is demonstrated with an O-terminated nanocrystalline-diamond (NCD) film as transducer material for the detection of pH and penicillin concentration. This has also been extended for the label-free electrical monitoring of adsorption and binding of charged macromolecules. One more recent study demonstrated a novel bio-sensing platform, which is introduced by combination of a) geometrically controlled DNA bonding using vertically aligned diamond nano-wires and b) the superior electrochemical sensing properties of diamond as transducer material. Diamond nanowires can be a new approach towards next generation electrochemical gene sensor platforms. This review highlights the advantages of these carbon materials to promote different electron transfer reactions specially those related to biomolecules. Different strategies have been applied for constructing carbon material-based electrochemical sensors, their analytical performance and future prospects are discussed

Synthesis of bio-functional nanomaterials in reactive plasma discharges

Plasma processing technologies have been extensively used as surface modification platforms in many biomedical applications. Particularly, plasma polymerization (PP) is a versatile deposition technology which has the potential to deliver biocompatible interfaces for a myriad of medical devices. To successfully translate new materials for specific clinical applications, the plasma process needs to be scalable and incorporate appropriate control feedback strategies. However, the plasma medium in PP is exceptionally complex and identifying the main physical quantities that allow a suitable formulation and description of the interface growth mechanisms is challenging. The first part of the thesis reports the design and optimization of a single step ion assisted PP process to create plasma-activated coatings (PAC) that meet the extreme mechanical demands for cardiovascular implants and in particular stents. An ideal working window in the parameter space is identified, and found suitable for the synthesis of PAC interfaces that are mechanically robust, hemocompatibility and allow one step covalent protein immobilization without the need for chemical processes. This window is identified by combining plasma optical emission spectroscopy (OES) with a comprehensive macroscopic process description that isolates key coating growth mechanisms. During process scalability, OES diagnostics revealed the formation of plasma polymer nanoparticles (nanoP3), usually known as plasma dust, in parallel with the deposition of PAC coatings. The second part of the thesis reports the demonstration of carbonaceous plasma nanoparticles for nanomedicine applications. By controlling nanoparticle formation and collection, nanoP3 were engineered with unique immobilization capabilities facilitating multifunctional nanocarriers. The unique surface chemistry of nanoP3, allowing a robust immobilization of the cargo without the need for intermediate functionalization strategies, has great potential to overcome major limitations of currently proposed platforms. As many of the favorable characteristics of nanoP3 are inherent to the fabrication process, this work proposes PP as a nanoparticle synthesis route with valuable potential for broad clinical and commercial applications

Anisotropic surface properties of micro/nanostructured a-C:H:F thin films with self-assembly applications

The singular properties of hydrogenated amorphous carbon (a-C:H) thin filmsdeposited by pulsed DC plasma enhanced chemical vapor deposition (PECVD), such as hardness and wear resistance, make it suitable as protective coating with low surface energy for self-assembly applications. In this paper, we designed fluorine-containing a-C:H (a-C:H:F) nanostructured surfaces and we characterized them for self-assembly applications. Sub-micron patterns were generated on silicon through laser lithography while contact angle measurements, nanotribometer, atomic force microscopy (AFM), and scanning electron microscopy (SEM) were used to characterize the surface. a-C:H:F properties on lithographied surfaces such as hydrophobicity and friction were improved with the proper relative quantity of CH4 and CHF3 during deposition, resulting in ultrahydrophobic samples and low friction coefficients. Furthermore, these properties were enhanced along the direction of the lithographypatterns (in-plane anisotropy). Finally, self-assembly properties were tested with silicananoparticles, which were successfully assembled in linear arrays following the generated patterns. Among the main applications, these surfaces could be suitable as particle filter selector and cell colony substrate

Blood protein and platelet interactions on surface engineered biomaterials

Modification of surfaces to improve the thrombo-resistance of a synthetic biomaterial is a vital aspect in the design of haemocompatible surfaces. Recent work suggests a non-haemocompatible surface may ubiquitously adsorb specific plasma proteins that form a proteinacious layer which mediates the adhesion and activation of platelets and rejection of the material and subsequently, the implanted medical device. Currently, apart from surface chemistry and wetability of the surface, preferential adsorption of specific proteins, their exact interaction and the effect of physical and spatial cues from the nano-environment prevents us from acknowledging a general interplay between biomaterials, proteins and platelets. Thus this study aims to investigate the effect of plasma protein adsorption and subsequent platelet interactions on the smooth and nano-patterned commercially used surface coatings such as hydrogenated amorphous carbon (a-C:H), tetrahedral amorphous carbon (ta-C) and titania (TiO2) surfaces. Results have shown a-C:H and ta-C surfaces exhibited increased affinity to fibrinogen than TiO2, while facilitating similar levels of platelet attachment. A-C:H resulted in decreased cellular spreading when compared with ta-C and TiO2, while same level of platelet activation was detected indicating that platelets could exist in their activated state without spreading. When platelet interactions on nano-patterned surfaces (RMS 5-8nm) were compared against flat surfaces, nano-rough surfaces presented with increased levels of platelet attachment as well as its spreading, while similar levels of platelet activation was detected amongst the smooth and rough substrates. Increased levels of platelet adhesion and spreading were positively correlated with increased fibrinogen adsorption, reinforcing the crucial role of fibrinogen in platelet binding but also its possible role in platelet spreading

Surface analysis of Detonation Nanodiamond thin films fabricated using automated spray coating technique

In recent years, Detonation Nanodiamond (DND) has gained importance as a biomaterial. DND can be made into thin film coating on substrates, which is a requirement for many bioanalytical sensing devices. In this work, the distribution and thickness of DND coated as thin film on silicon substrate were studied. The coating was performed using an automated spray coating device designed for thin film deposition. The spray coated samples were compared with samples fabricated by spin coating. Scanning Electron Microscopy (SEM) was used as the analysis tool to analyse the distribution and thickness of the thin film samples. DNDs were observed as densely packed agglomerates on the surface of the thin film coatings. Agglomeration causes the DND particles to form clusters resulting in unevenness of coating surface. To prevent agglomeration and improve evenness of coating, deagglomeration is carried out using ultrasonication. The core aggregates were left intact, and the smallest observable aggregates were no less than 10nm. The thickness of DND coated thin films was measured using SEM. Thickness measurements show the coating to be uneven, which is expected to occur due to agglomeration. The average thickness of spray coating samples lies between 450 – 550 nm and that of spin coated samples lie between 200-300 nm for the same amount of solution consumption per unit area. Delamination of DND coating from Silicon substrate occurred due to the intense grinding and polishing processes during sample preparation for SEM analysis, which decreases the evenness of coating and accuracy of measurements. Improved sample preparation methods are required to obtain accurate thickness measurement using SEM. Further improvements on deagglomeration techniques might improve the distribution of DND particles, and consistency of coating thickness in DND thin film coatings. SEM has resolution power in the nanometre scale making it a good analysis tool to measure the distribution of the thin film coatings. Nevertheless, it was not possible to observe primary DND particles with good resolution below 100 nm scale using SEM. SEM along with improved sample preparation methods could possibly be a good analysis tool for thickness measurements, as it is required to fabricate measurable and repeatable thin film coatings in industrial scale

Nanomedicine for the reduction of the thrombogenicity of stent coatings

The treatment of patients with drug-eluting stents (DES) continues to evolve with the current emergence of DES technology that offers a combination of pharmacological and mechanical approaches to prevent arterial restenosis. However, despite the promising short-term and mid-term outcomes of DES, there are valid concerns about adverse clinical effects of late stent thrombosis. In this study, we present an example of how nanomedicine can offer solutions for improving stent coating manufacturing, by producing nanomaterials with tailored and controllable properties. The study is based on the exploitation of human platelets response towards carbon-based nanocoatings via atomic force microscope (AFM). AFM can facilitate the comprehensive analysis of platelets behavior onto stent nanocoatings and enable the study of thrombogenicity. Platelet-rich plasma from healthy donors was used for the real-time study of biointerfacial interactions. The carbon nanomaterials were developed by rf magnetron sputtering technique under controllable deposition conditions to provide favorable surface nanotopography. It was shown that by altering the surface topography of nanocoatings, the activation of platelets can be affected, while the carbon nanocoatings having higher surface roughness were found to be less thrombogenic in terms of platelets adhesion. This is an actual solution for improving the stent coating fabrication

Carbon Nanomaterials and their application to Electrochemical Sensors: A review

Carbon has long been applied as an electrochemical sensing interface owing to its unique electrochemical properties. Moreover, recent advances in material design and synthesis, particularly nanomaterials, has produced robust electrochemical sensing systems that display superior analytical performance. Carbon nanotubes (CNTs) are one of the most extensively studied nanostructures because of their unique properties. In terms of electroanalysis, the ability of CNTs to augment the electrochemical reactivity of important biomolecules and promote electron transfer reactions of proteins is of particular interest. The remarkable sensitivity of CNTs to changes in surface conductivity due to the presence of adsorbates permits their application as highly sensitive nanoscale sensors. CNT-modified electrodes have also demonstrated their utility as anchors for biomolecules such as nucleic acids, and their ability to diminish surface fouling effects. Consequently, CNTs are highly attractive to researchers as a basis for many electrochemical sensors. Similarly, synthetic diamonds electrochemical properties, such as superior chemical inertness and biocompatibility, make it desirable both for (bio) chemical sensing and as the electrochemical interface for biological systems. This is highlighted by the recent development of multiple electrochemical diamond-based biosensors and bio interfaces