Eleonora Macchia

Tailoring Functional Interlayers in Organic Field‐Effect Transistor Biosensors

This review aims to provide an update on the development involving dielectric/organic semiconductor (OSC) interfaces for the realization of biofunctional organic field-effect transistors (OFETs). Specific focus is given on biointerfaces and recent technological approaches where biological materials serve as interlayers in back-gated OFETs for biosensing applications. Initially, to better understand the effects produced by the presence of biomolecules deposited at the dielectric/OSC interfacial region, the tuning of the dielectric surface properties by means of self-assembled monolayers is discussed. Afterward, emphasis is given to the modification of solid-state dielectric surfaces, in particular inorganic dielectrics, with biological molecules such as peptides and proteins. Special attention is paid on how the presence of an interlayer of biomolecules and bioreceptors underneath the OSC impacts on the charge transport and sensing performance of the device. Moreover, naturally occurring materials, such as carbohydrates and DNA, used directly as bulk gating materials in OFETs are reviewed. The role of metal contact/OSC interface in the overall performance of OFET-based sensors is also discussed.

Printable and flexible electronics: From TFTs to bioelectronic devices

Printable and flexible thin-film transistors (TFTs) have gained significant attention over the last few years thanks to their implementation in many different sectors. Beside applications in large-area electronics such as flat displays, sensors and radio frequency identification tags, these devices have been widely investigated for life sciences applications too, including label-free biosensors, systems for drug delivery and implantable platforms. This review highlights the recent advances in the field of highly performing low-cost TFT devices realized by printing or printing compatible technologies and suitable for bioelectronics applications. Novel printable materials used as semiconductors, dielectrics and electrodes as well as printing technologies useful for the realization of the elicited devices are discussed as well. Particularly attention is given to printing techniques employed for the deposition of biological materials and to methods for realizing label-free electronic biosensors.

Organic bioelectronics probing conformational changes in surface confined proteins

The study of proteins confined on a surface has attracted a great deal of attention due to its relevance in the development of bio-systems for laboratory and clinical settings. In this respect, organic bio-electronic platforms can be used as tools to achieve a deeper understanding of the processes involving protein interfaces. In this work, biotin-binding proteins have been integrated in two different organic thin-film transistor (TFT) configurations to separately address the changes occurring in the protein-ligand complex morphology and dipole moment. This has been achieved by decoupling the output current change upon binding, taken as the transducing signal, into its component figures of merit. In particular, the threshold voltage is related to the protein dipole moment, while the field-effect mobility is associated with conformational changes occurring in the proteins of the layer when ligand binding occurs. Molecular Dynamics simulations on the whole avidin tetramer in presence and absence of ligands were carried out, to evaluate how the tight interactions with the ligand affect the protein dipole moment and the conformation of the loops surrounding the binding pocket. These simulations allow assembling a rather complete picture of the studied interaction processes and support the interpretation of the experimental results.

An analytical model for bio-electronic organic field-effect transistor sensors

A model for the electrical characteristics of Functional-Bio-Interlayer Organic Field-Effect Transistors (FBI-OFETs) electronic sensors is here proposed. Specifically, the output current-voltage characteristics of a streptavidin (SA) embedding FBI-OFET are modeled by means of the analytical equations of an enhancement mode p-channel OFET modified according to an ad hoc designed equivalent circuit that is also independently simulated with pspice. An excellent agreement between the model and the experimental current-voltage output characteristics has been found upon exposure to 5 nM of biotin. A good agreement is also found with the SA OFET parameters graphically extracted from the device transfer I-V curves.

Characterization of Covalently Bound Anti-Human Immunoglobulins on Self-Assembled Monolayer Modified Gold Electrodes

Bioconjugated gold surfaces constitute interesting platforms for biosensing applications. The immobilization of antibodies such as anti‐immunoglobulin G and M (anti‐IgG and anti‐IgM) on gold electrodes via self‐assembled monolayers (SAMs) is here studied as a model system for further immunoassays development. The biolayer is characterized by means of X‐ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), a dedicated thin‐film transistor (TFT)‐based platform and electrochemical surface plasmon resonance (EC‐SPR). XPS analysis confirms the presence of all the chemical species involved in the fabrication process as well as the covalent attachment of the antibodies with high reproducibility. Visualization of the biolayer topography by AFM shows nanostructures with a thickness consistent with the actual size of the protein, which is also verified by SPR measurements. EC‐SPR allows taking advantage of complementary electrochemical and optical signals during the functionalization steps. Moreover, the functionalization of gold leads to a change in the work function, which is demonstrated in an electrolyte gated thin‐film transistor configuration. Such configuration enables also to evaluate the electrostatic changes occurring on the gate that are connected with the threshold voltage shifts. The data support that functional biomodified gold surfaces can be reproducibly prepared, which is a prerequisite for further biosensor development.

Electrolyte gated TFT biosensors based on the Donnan's capacitance of anchored biomolecules

Biodetection using electrolyte gated field effect transistors has been mainly correlated to charge modulated transduction. Therefore, such platforms are designed and studied for limited applications involving relatively small charged species and much care is taken in the operating conditions particularly pH and salt concentration (ionic strength). However, there are several reports suggesting that the device conductance can also be very sensitive towards variations in the capacitance coupling. Understanding the sensing mechanism is important for further exploitation of these promising sensors in broader range of applications. In this paper, we present a thorough and in depth study of a multilayer protein system coupled to an electrolyte gated transistor. It is demonstrated that detection associated to a binding event taking place at a distance of 30 nm far from the organic semiconductor-electrolyte interface is possible and the device conductance is dominated by Donnan’s capacitance of anchored biomolecules.

Correction: Printable and flexible electronics: from TFTs to bioelectronic devices

Correction for ‘Printable and flexible electronics: from TFTs to bioelectronic devices’ by M. Magliulo et al., J. Mater. Chem. C, 2015, 3, 12347–12363.

Direct electronic probing of biological complexes formation

Functional bio-interlayer organic field - effect transistors (FBI-OFET), embedding streptavidin, avidin and neutravidin as bio-recognition element, have been studied to probe the electronic properties of protein complexes. The threshold voltage control has been achieved modifying the SiO2 gate diaelectric surface by means of the deposition of an interlayer of bio-recognition elements. A threshold voltage shift with respect to the unmodified dielectric surface toward more negative potential values has been found for the three different proteins, in agreement with their isoelectric points. The relative responses in terms of source – drain current, mobility and threshold voltage upon exposure to biotin of the FBI-OFET devices have been compared for the three bio-recognition elements.

Single-molecule detection with a millimetre-sized transistor

Label-free single-molecule detection has been achieved so far by funnelling a large number of ligands into a sequence of single-binding events with few recognition elements host on nanometric transducers. Such approaches are inherently unable to sense a cue in a bulk milieu. Conceptualizing cells’ ability to sense at the physical limit by means of highly-packed recognition elements, a millimetric sized field-effect-transistor is used to detect a single molecule. To this end, the gate is bio-functionalized with a self-assembled-monolayer of 1012 capturing anti-Immunoglobulin-G and is endowed with a hydrogen-bonding network enabling cooperative interactions. The selective and label-free single molecule IgG detection is strikingly demonstrated in diluted saliva while 15 IgGs are assayed in whole serum. The suggested sensing mechanism, triggered by the affinity binding event, involves a work-function change that is assumed to propagate in the gating-field through the electrostatic hydrogen-bonding network. The proposed immunoassay platform is general and can revolutionize the current approach to protein detection.The sensing capability of nanometric transducers designed for label-free single molecule detection has been limited by the small number of recognition elements. Here, the authors demonstrate a millimetre-sized field effect transistor capable of selective single-molecule Immunoglobulin-G detection.

Organic electrochemical transistor immuno-sensor operating at the femto-molar limit of detection

The interfacing of biomaterials to electronic devices is one of the most challenging research fields that has relevance to both fundamental studies and the development of highly performing biosensors. Organic Electrochemical transistors, using an aqueous electrolyte solution, offer a unique set of advantages in the development of biosensor devices. In this paper, we report highly selective organic electrochemical transistor based immune-sensor by modifying the gate electrode with polyclonal anti-human Immunoglobulin G (anti-IgG) antibodies. Extremely low detection of Immunoglobulin G (IgG) at the femto-molar detection limit has been achieved.