Nicola Martino

A polymer optoelectronic interface restores light sensitivity in blind rat retinas

Interfacing organic electronics with biological substrates offers new possibilities for biotechnology due to the beneficial properties exhibited by organic conducting polymers. These polymers have been used for cellular interfaces in several fashions, including cellular scaffolds, neural probes, biosensors and actuators for drug release. Recently, an organic photovoltaic blend has been exploited for neuronal stimulation via a photo-excitation process. Here, we document the use of a single-component organic film of poly(3-hexylthiophene) (P3HT) to trigger neuronal firing upon illumination. Moreover, we demonstrate that this bio-organic interface restored light sensitivity in explants of rat retinas with light-induced photoreceptor degeneration. These findings suggest that all-organic devices may play an important future role in sub-retinal prosthetic implants.

Sub-Micrometer Charge Modulation Microscopy of a High Mobility Polymeric n-Channel Field-Effect Transistor

After two decades of fundamental research and steady development, solution processable organic fi eld-effect transistors (OFETs) have recently reached a mature stage that preludes their adoption in a variety of commercial applications from light-weight, stretchable, large-area sensors to low-cost, fl exible electronic circuits. [ 1–5 ] Despite the fact that fi eld-effect mobilities ( μ fe ) exceeding 1 cm 2 V − 1 s − 1 for both pand n-channel OFETs are now achievable with commercial, off-the-shelf conjugated organic small molecules and polymers, [ 4 ] fundamental studies are still strongly needed because of an incomplete understanding of the main mechanisms governing charge injection and transport in such devices. [ 7–9 ] To this extent, probing techniques capable of providing local information regarding mobility, fi eld, and charge distribution along the channel of a working device would be greatly benefi cial. Of particular interest for organic semiconductors is the relationship between microstructure and charge transport properties. This is even more evident in the case of recently developed high-mobility and stable n-channel OFETs, [ 6 ] in which the unusual face-on orientation of molecules has confounded expectations of what is required for effective charge transport. Scanning Kelvin-probe miscroscopy (SKPM) [ 7 ] is a powerful technique that allowed to map the potential profi le along the channels of OFETs with resolution better than 50 nm. [ 8 , 9 ]

Photothermal cellular stimulation in functional bio-polymer interfaces

Hybrid interfaces between organic semiconductors and living tissues represent a new tool for in-vitro and in-vivo applications, bearing a huge potential, from basic researches to clinical applications. In particular, light sensitive conjugated polymers can be exploited as a new approach for optical modulation of cellular activity. In this work we focus on light-induced changes in the membrane potential of Human Embryonic Kidney (HEK-293) cells grown on top of a poly(3-hexylthiophene) (P3HT) thin film. On top of a capacitive charging of the polymer interface, we identify and fully characterize two concomitant mechanisms, leading to membrane depolarization and hyperpolarisation, both mediated by a thermal effect. Our results can be usefully exploited in the creation of a new platform for light-controlled cell manipulation, with possible applications in neuroscience and medicine.

Photostimulation of Whole-Cell Conductance in Primary Rat Neocortical Astrocytes Mediated by Organic Semiconducting Thin Films

Astroglial ion channels are fundamental molecular targets in the study of brain physiology and pathophysiology. Novel tools and devices intended for stimulation and control of astrocytes ion channel activity are therefore highly desirable. The study of the interactions between astrocytes and biomaterials is also essential to control and minimize reactive astrogliosis, in view of the development of implantable functional devices. Here, the growth of rat primary neocortical astrocytes on the top of a light sensitive, organic polymer film is reported; by means of patch-clamp analyses, the effect of the visible light stimulation on membrane conductance is then determined. Photoexcitation of the active material causes a significant depolarization of the astroglial resting membrane potential: the effect is associated to an increase in whole-cell conductance at negative potentials. The magnitude of the evoked inward current density is proportional to the illumination intensity. Biophysical and pharmacological characterization suggests that the ion channel mediating the photo-transduction mechanism is a chloride channel, the ClC-2 channel. These results open interesting perspectives for the selective manipulation of astrocyte bioelectrical activity by non-invasive, label-free, organic-based, photostimulation approaches.

Light-evoked hyperpolarization and silencing of neurons by conjugated polymers.

The ability to control and modulate the action potential firing in neurons represents a powerful tool for neuroscience research and clinical applications. While neuronal excitation has been achieved with many tools, including electrical and optical stimulation, hyperpolarization and neuronal inhibition are typically obtained through patch-clamp or optogenetic manipulations. Here we report the use of conjugated polymer films interfaced with neurons for inducing a light-mediated inhibition of their electrical activity. We show that prolonged illumination of the interface triggers a sustained hyperpolarization of the neuronal membrane that significantly reduces both spontaneous and evoked action potential firing. We demonstrate that the polymeric interface can be activated by either visible or infrared light and is capable of modulating neuronal activity in brain slices and explanted retinas. These findings prove the ability of conjugated polymers to tune neuronal firing and suggest their potential application for the in-vivo modulation of neuronal activity.

Mapping Orientational Order of Charge-Probed Domains in a Semiconducting Polymer

Structure-property relationships are of fundamental importance to develop quantitative models describing charge transport in organic semiconductor based electronic devices, which are among the best candidates for future portable and lightweight electronic applications. While microstructural investigations, such as those based on X-rays, electron microscopy, or polarized optical probes, provide necessary information for the rationalization of transport in macromolecular solids, a general model predicting how charge accommodates within structural maps is not yet available. Therefore, techniques capable of directly monitoring how charge is distributed when injected into a polymer film and how it correlates to structural domains can help fill this gap. Supported by density functional theory calculations, here we show that polarized charge modulation microscopy (p-CMM) can unambiguously and selectively map the orientational order of the only conjugated segments that are probed by mobile charge in the few nanometer thick accumulation layer of a high-mobility polymer-based field-effect transistor . Depending on the specific solvent-induced microstructure within the accumulation layer, we show that p-CMM can image charge-probed domains that extend from submicrometer to tens of micrometers size, with markedly different degrees of alignment. Wider and more ordered p-CMM domains are associated with improved carrier mobility, as extracted from device characteristics. This observation evidences the unprecedented opportunity to correlate, directly in a working device, electronic properties with structural information on those conjugated segments involved in charge transport at the buried semiconductor-dielectric interface of a field-effect device.

Conjugated polymers for the optical control of the electrical activity of living cells

The possibility to optically excite the electrical activity of living cells by using exogenous absorbers is gaining more and more interest in the neuroscience and biotechnology community. Conjugated polymers, inherently sensitive to visible light, were recently proposed as candidates to this goal. To date, however, only one polymer type, namely regio-regular poly-3-hexylthiophene, has been tested as the active material. In this work four different conjugated polymers, regarded as prototypes of their category, are investigated as photoactive bio-interfaces. The selected materials have different absorption spectra, morphology, light emission efficiency and charge transport properties. We analyze their key-enabling properties, such as electrochemical stability, surface morphology, wettability, sterilization compatibility, interaction with protein adhesion layers and toxicity, throughout all the necessary steps for the realization of an efficient bio-optical interface. We demonstrate that all considered polymers are characterized by good biocompatibility and cell seeding properties, and can optimally sustain thermal sterilization. Conversely, electrochemical stability and cell photostimulation efficacy can vary a lot among different materials, and should be carefully evaluated case by case. Reported results represent the starting point for the implementation of bio-polymer interfaces sensitive to different colors and, in perspective, for the realization of a three-chromatic artificial visual prosthesis.

Shedding Light on Living Cells

An overview of the optical methods available to modulate the cellular activity in cell cultures and biological tissues is presented, with a focus on the use of exogenous functional materials that absorb electromagnetic radiation and transduce it into a secondary stimulus for cell excitation, with high temporal and spatial resolution. Both organic and inorganic materials are critically evaluated, for in vitro and in vivo applications. Finally, as a direct practical application of optical-stimulation techniques, the most recent results in the realization of artificial visual implants are discussed.

Optical Control of Living Cells Electrical Activity by Conjugated Polymers.

Hybrid interfaces between organic semiconductors and living tissues represent a new tool for in-vitro and in-vivo applications. In particular, conjugated polymers display several optimal properties as substrates for biological systems, such as good biocompatibility, excellent mechanical properties, cheap and easy processing technology, and possibility of deposition on light, thin and flexible substrates. These materials have been employed for cellular interfaces like neural probes, transistors for excitation and recording of neural activity, biosensors and actuators for drug release. Recent experiments have also demonstrated the possibility to use conjugated polymers for all-optical modulation of the electrical activity of cells. Several in-vitro study cases have been reported, including primary neuronal networks, astrocytes and secondary line cells. Moreover, signal photo-transduction mediated by organic polymers has been shown to restore light sensitivity in degenerated retinas, suggesting that these devices may be used for artificial retinal prosthesis in the future. All in all, light sensitive conjugated polymers represent a new approach for optical modulation of cellular activity. In this work, all the steps required to fabricate a bio-polymer interface for optical excitation of living cells are described. The function of the active interface is to transduce the light stimulus into a modulation of the cell membrane potential. As a study case, useful for in-vitro studies, a polythiophene thin film is used as the functional, light absorbing layer, and Human Embryonic Kidney (HEK-293) cells are employed as the biological component of the interface. Practical examples of successful control of the cell membrane potential upon stimulation with light pulses of different duration are provided. In particular, it is shown that both depolarizing and hyperpolarizing effects on the cell membrane can be achieved depending on the duration of the light stimulus. The reported protocol is of general validity and can be straightforwardly extended to other biological preparations.

Controlling cell functions by light

The capability to selectively affect vital functions in cell networks and sub-cell compartments in vitro or in vivo is a mission critical tool in neuroscience and medicine. Optical excitation is one of the main strategies used to achieve high spatial and temporal resolution. In the following we describe recent results and future approaches of cell photostimulation mediated by organic semiconducting polymers.