Anna-Maria Pappa

Lactate Detection in Tumor Cell Cultures Using Organic Transistor Circuits

A biosensing platform based on an organic transistor circuit for metabolite detection in highly complex biological media is introduced. The sensor circuit provides inherent background subtraction allowing for highly specific, sensitive lactate detection in tumor cell cultures. The proposed sensing platform paves the way toward rapid, label-free, and cost-effective clinically relevant in vitro diagnostic tools.

A Microfluidic Ion Pump for In Vivo Drug Delivery

Implantable devices offer an alternative to systemic delivery of drugs for the treatment of neurological disorders. A microfluidic ion pump (µFIP), capable of delivering a drug without the solvent through electrophoresis, is developed. The device is characterized in vitro by delivering γ-amino butyric acid to a target solution, and demonstrates low-voltage operation, high drug-delivery capacity, and high ON/OFF ratio. It is also demonstrated that the device is suitable for cortical delivery in vivo by manipulating the local ion concentration in an animal model and altering neural behavior. These results show that µFIPs represent a significant step forward toward the development of implantable drug-delivery systems.

Electrospray-Processed Soluble Acenes toward the Realization of High-Performance Field-Effect Transistors

Functionalized acenes have proven to be promising compounds in the field of molecular electronics because of their unique features in terms of the stability, performance, and ease of processing. The emerging concept of large-area-compatible techniques for flexible electronics has brought about a wide variety of well-established techniques for the deposition of soluble acenes, with spray-coating representing an especially fruitful approach. In the present study, electrostatic spray deposition is proposed as an alternative to the conventional spray-coating processes, toward the realization of high-performance organic field-effect transistors (OFETs), on both rigid and flexible substrates. Particularly, a thorough study on the effect of the solvent and spraying regime on the resulting crystalline films morphology is performed. By optimization of the process conditions in terms of control over the size as well as the crystallization scheme of the droplets, desirable morphological features along with high-quality crystal domains are obtained. The fabricated OFETs exhibit excellent electrical characteristics, with high field-effect mobility up to 0.78 cm(2)/(V s), I(on)/I(off) >10(4), and near-zero threshold voltages. Additionally, the good performance of the OFETs realized on plastic substrates gives great potentiality to the proposed method for applications in the challenging field of large-area electronics.

High mobility transistors based on electrospray-printed small-molecule/polymer semiconducting blends

Spray-coating techniques have recently emerged as especially effective approaches for the deposition of small semiconducting molecules toward the fabrication of organic field-effect transistors (OFETs). Despite the promising mobility values and the industrial implementation capability of such techniques, the resultant devices still face challenges in terms of morphology control and performance variation. In this work, the efficient process control of electrostatic spraying deposition (ESD) and the excellent film forming properties of polymer:small molecule blends were successfully combined to develop reliable and high performance transistors. Specifically, a highly efficient blended system of 2,8-difluoro-5,11-bis(triethylsilylethynyl)-anthradithiophene (diF-TES-ADT) and poly(triarylamine) (PTAA) was employed in order to realize top-gate OFETs under ambient conditions, both on rigid and on flexible substrates. The films revealed extensive crystallization and microstructural organization implying distinct phase separation in the electrosprayed blend. Furthermore, we investigated the effect of processing temperature on film continuity and the presence of grain boundaries. Remarkably, the electrosprayed OFETs exhibited field-effect mobilities as high as 1.7 cm2 V−1 s−1 and enhanced performance consistency when compared to conventional gas-sprayed transistors. Additionally, the transistors showed excellent electrical and environmental stability, indicative of the good interface quality and the self-encapsulation capability of the top-gate structure. These results highlight the great potential of electrohydrodynamic atomization techniques for implementation in large-area processing for OFET fabrication.

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are two-fold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.

Conducting Polymer Scaffolds for Hosting and Monitoring 3D Cell Culture

This work reports the design of a live‐cell monitoring platform based on a macroporous scaffold of a conducting polymer, poly(3,4‐ethylene dioxythiophene):poly(styrenesulfonate). The conducting polymer scaffolds support 3D cell cultures due to their biocompatibility and tissue‐like elasticity, which can be manipulated by inclusion of biopolymers such as collagen. Integration of a media perfusion tube inside the scaffold enables homogenous cell spreading and fluid transport throughout the scaffold, ensuring long term cell viability. This also allows for co‐culture of multiple cell types inside the scaffold. The inclusion of cells within the porous architecture affects the impedance of the electrically conducting polymer network and, thus, is utilized as an in situ tool to monitor cell growth. Therefore, while being an integral part of the 3D tissue, the conducting polymer is an active component, enhancing the tissue function, and forming the basis for a bioelectronic device with integrated sensing capability.

Polyelectrolyte Layer-by-Layer Assembly on Organic Electrochemical Transistors

Oppositely charged polyelectrolyte multilayers (PEMs) were built up in a layer-by-layer (LbL) assembly on top of the conducting polymer channel of an organic electrochemical transistor (OECT), aiming to combine the advantages of well-established PEMs with a high performance electronic transducer. The multilayered film is a model system to investigate the impact of biofunctionalization on the operation of OECTs comprising a poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) film as the electrically active layer. Understanding the mechanism of ion injection into the channel that is in direct contact with charged polymer films provides useful insights for novel biosensing applications such as nucleic acid sensing. Moreover, LbL is demonstrated to be a versatile electrode modification tool enabling tailored surface features in terms of thickness, softness, roughness, and charge. LbL assemblies built up on top of conducting polymers will aid the design of new bioelectronic platforms for drug delivery, tissue engineering, and medical diagnostics.

Organic Electronics for Point-of-Care Metabolite Monitoring

In this review we focus on demonstrating how organic electronic materials can solve key problems in biosensing thanks to their unique material properties and implementation in innovative device configurations. We highlight specific examples where these materials solve multiple issues related to complex sensing environments, and we benchmark these examples by comparing them to state-of-the-art commercially available sensing using alternative technologies. We have categorized our examples by sample type, focusing on sensing from body fluids in vitro and on wearable sensors, which have attracted significant interest owing to their integration with everyday life activities. We finish by describing a future trend for in vivo, implantable sensors, which aims to build on current progress from sensing in biological fluids ex vivo.

Electrophoretic drug delivery for seizure control

An implantable microfluidic ion pump prevents seizures in a mice by delivery of inhibitory neurotransmitters to the seizure source. The persistence of intractable neurological disorders necessitates novel therapeutic solutions. We demonstrate the utility of direct in situ electrophoretic drug delivery to treat neurological disorders. We present a neural probe incorporating a microfluidic ion pump (μFIP) for on-demand drug delivery and electrodes for recording local neural activity. The μFIP works by electrophoretically pumping ions across an ion exchange membrane and thereby delivers only the drug of interest and not the solvent. This “dry” delivery enables precise drug release into the brain region with negligible local pressure increase. The therapeutic potential of the μFIP probe is tested in a rodent model of epilepsy. The μFIP probe can detect pathological activity and then intervene to stop seizures by delivering inhibitory neurotransmitters directly to the seizure source. We anticipate that further tailored engineering of the μFIP platform will enable additional applications in neural interfacing and the treatment of neurological disorders.

Biomimetic Electronic Devices for Measuring Bacterial Membrane Disruption

Antibiotic discovery has experienced a severe slowdown in terms of discovery of new candidates. In vitro screening methods using phospholipids to model the bacterial membrane provide a route to identify molecules that specifically disrupt bacterial membranes causing cell death. Thanks to the electrically insulating properties of the major component of the cell membrane, phospholipids, electronic devices are highly suitable transducers of membrane disruption. The organic electrochemical transistor (OECT) is a highly sensitive ion-to-electron converter. Here, the OECT is used as a transducer of the permeability of a lipid monolayer (ML) at a liquid:liquid interface, designed to read out changes in ion flux caused by compounds that interact with, and disrupt, lipid assembly. This concept is illustrated using the well-documented antibiotic Polymixin B and the highly sensitive quantitation of permeability of the lipid ML induced by two novel recently described antibacterial amine-based oligothioetheramides is shown, highlighting molecular scale differences in their disruption capabilities. It is anticipated that this platform has the potential to play a role in front-line antimicrobial compound design and characterization thanks to the compatibility of semiconductor microfabrication technology with high-throughput readouts.