Staff member

Rubén Millán Solsona

Senior Technician
Nanoscale Bioelectrical Characterization
+34 934 031 184
Staff member publications

Kyndiah, A., Leonardi, F., Tarantino, C., Cramer, T., Millan-Solsona, R., Garreta, E., Montserrat, N., Mas-Torrent, M., Gomila, G., (2020). Bioelectronic recordings of cardiomyocytes with accumulation mode electrolyte gated organic field effect transistors Biosensors and Bioelectronics 150, 111844

Organic electronic materials offer an untapped potential for novel tools for low-invasive electrophysiological recording and stimulation devices. Such materials combine semiconducting properties with tailored surface chemistry, elastic mechanical properties and chemical stability in water. In this work, we investigate solution processed Electrolyte Gated Organic Field Effect Transistors (EGOFETs) based on a small molecule semiconductor. We demonstrate that EGOFETs based on a blend of soluble organic semiconductor 2,8-Difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene (diF-TES-ADT) combined with an insulating polymer show excellent sensitivity and long-term recording under electrophysiological applications. Our devices can stably record the extracellular potential of human pluripotent stem cell derived cardiomyocyte cells (hPSCs-CMs) for several weeks. In addition, cytotoxicity tests of pharmaceutical drugs, such as Norepinephrine and Verapamil was achieved with excellent sensitivity. This work demonstrates that organic transistors based on organic blends are excellent bioelectronics transducer for extracellular electrical recording of excitable cells and tissues thus providing a valid alternative to electrochemical transistors.

Keywords: Bioelectronics, Cardiac cells, Organic electronics, Organic field effect transistors, Organic semiconducting blend

Muzio, Martina Di, Millan-Solsona, Ruben, Borrell, Jordi H., Fumagalli, Laura, Gomila, Gabriel, (2020). Cholesterol effect on the specific capacitance of submicrometric DOPC bilayer patches measured by in-liquid scanning dielectric microscopy Langmuir 36, (43), 12963–12972

The specific capacitance of biological membranes is a key physical parameter in bioelectricity that also provides valuable physicochemical information on composition, phase, or hydration properties. Cholesterol is known to modulate the physicochemical properties of biomembranes, but its effect on the specific capacitance has not been fully established yet. Here we use the high spatial resolution capabilities of in-liquid scanning dielectric microscopy in force detection mode to directly demonstrate that DOPC bilayer patches at 50% cholesterol concentration show a strong reduction of their specific capacitance with respect to pure DOPC bilayer patches. The reduction observed (around 35%) cannot be explained by the small increase in bilayer thickness (around 16%). We suggest that the reduction of the specific capacitance might be due to the dehydration of the polar head groups caused by the insertion of cholesterol molecules in the bilayer. The results reported confirm the potential of in-liquid SDM to study the electrical and physicochemical properties of lipid bilayers at very small scales (down to around 200 nm here), with implications in fields such as biophysics, bioelectricity, biochemistry, and biosensing.

Millán, Rubén, Checa, Marti, Fumagalli, Laura, Gomila, Gabriel, (2020). Mapping the capacitance of self-assembled monolayers at metal/electrolyte interfaces at the nanoscale by In-liquid scanning dielectric microscopy Nanoscale In press

Organic self-assembled monolayers (SAMs) at metal/electrolyte interfaces have been thoroughly investigated both from fundamental and applied points of views. A relevant figure of merit of metal/SAM/electrolyte interfaces is the specific capacitance, which determines the charge that can be accumulated at the metal electrode. Here, we show that the specific capacitance of non-uniform alkanethiol SAMs at gold/electrolyte interfaces can be quantitatively measured and mapped at the nanoscale with in-liquid Scanning Dielectric Microscopy in force detection mode. We show that sub-100 nm spatial resolution in ultrathin (< 1 nm) SAMs can be achieved, largely improving the performance of current sensing characterization techniques. Present results open the access to study the dielectric properties of metal/SAM/electrolyte interfaces at scales that have remained unexplored until now.

Kyndiah, Adrica, Checa, Martí, Leonardi, Francesca, Millan-Solsona, Ruben, Di Muzio, Martina, Tanwar, Shubham, Fumagalli, Laura, Mas-Torrent, Marta, Gomila, Gabriel, (2020). Nanoscale mapping of the conductivity and interfacial capacitance of an electrolyte-gated organic field-effect transistor under operation Advanced Functional Materials , (), 2008032

Probing nanoscale electrical properties of organic semiconducting materials at the interface with an electrolyte solution under externally applied voltages is key in the field of organic bioelectronics. It is demonstrated that the conductivity and interfacial capacitance of the active channel of an electrolyte-gated organic field‐effect transistor (EGOFET) under operation can be probed at the nanoscale using scanning dielectric microscopy in force detection mode in liquid environment. Local electrostatic force versus gate voltage transfer characteristics are obtained on the device and correlated with the global current–voltage transfer characteristics of the EGOFET. Nanoscale maps of the conductivity of the semiconducting channel show the dependence of the channel conductivity on the gate voltage and its variation along the channel due to the space charge limited conduction. The maps reveal very small electrical heterogeneities, which correspond to local interfacial capacitance variations due to an ultrathin non-uniform insulating layer resulting from a phase separation in the organic semiconducting blend. Present results offer insights into the transduction mechanism at the organic semiconductor/electrolyte interfaces at scales down to ≈100 nm, which can bring substantial optimization of organic electronic devices for bioelectronic applications such as electrical recording on excitable cells or label-free biosensing.

Checa, Marti, Millán, Rubén, Blanco, Núria, Torrents, Eduard, Fabregas, Rene, Gomila, Gabriel, (2019). Mapping the dielectric constant of a single bacterial cell at the nanoscale with scanning dielectric force volume microscopy Nanoscale 11, 20809-20819

Mapping the dielectric constant at the nanoscale of samples showing a complex topography, such as non-planar nanocomposite materials or single cells, poses formidable challenges to existing nanoscale dielectric microscopy techniques. Here we overcome these limitations by introducing Scanning Dielectric Force Volume Microscopy. This scanning probe microscopy technique is based on the acquisition of electrostatic force approach curves at every point of a sample and its post-processing and quantification by using a computational model that incorporates the actual measured sample topography. The technique provides quantitative nanoscale images of the local dielectric constant of the sample with unparalleled accuracy, spatial resolution and statistical significance, irrespectively of the complexity of its topography. We illustrate the potential of the technique by presenting a nanoscale dielectric constant map of a single bacterial cell, including its small-scale appendages. The bacterial cell shows three characteristic equivalent dielectric constant values, namely, εr,bac1=2.6±0.2, εr,bac2=3.6±0.4 and εr,bac3=4.9±0.5, which enable identifying different dielectric properties of the cell wall and of the cytoplasmatic region, as well as, the existence of variations in the dielectric constant along the bacterial cell wall itself. Scanning Dielectric Force Volume Microscopy is expected to have an important impact in Materials and Life Sciences where the mapping of the dielectric properties of samples showing complex nanoscale topographies is often needed.

Lozano, H., Millán-Solsona, R., Fabregas, R., Gomila, G., (2019). Sizing single nanoscale objects from polarization forces Scientific Reports 9, (1), 14142

Sizing natural or engineered single nanoscale objects is fundamental in many areas of science and technology. To achieve it several advanced microscopic techniques have been developed, mostly based on electron and scanning probe microscopies. Still for soft and poorly adhered samples the existing techniques face important challenges. Here, we propose an alternative method to size single nanoscale objects based on the measurement of its electric polarization. The method is based on Electrostatic Force Microscopy measurements combined with a specifically designed multiparameter quantification algorithm, which gives the physical dimensions (height and width) of the nanoscale object. The proposed method is validated with ~50 nm diameter silver nanowires, and successfully applied to ~10 nm diameter bacterial polar flagella, an example of soft and poorly adhered nanoscale object. We show that an accuracy comparable to AFM topographic imaging can be achieved. The main advantage of the proposed method is that, being based on the measurement of long-range polarization forces, it can be applied without contacting the sample, what is key when considering poorly adhered and soft nanoscale objects. Potential applications of the proposed method to a wide range of nanoscale objects relevant in Material, Life Sciences and Nanomedicine is envisaged.

Keywords: Characterization and analytical techniques, Imaging techniques

Torres-Sanchez, A., Millan, D., Arroyo, M., (2019). Modelling fluid deformable surfaces with an emphasis on biological interfaces Journal of Fluid Mechanics 872, 218-271

Fluid deformable surfaces are ubiquitous in cell and tissue biology, including lipid bilayers, the actomyosin cortex or epithelial cell sheets. These interfaces exhibit a complex interplay between elasticity, low Reynolds number interfacial hydrodynamics, chemistry and geometry, and govern important biological processes such as cellular traffic, division, migration or tissue morphogenesis. To address the modelling challenges posed by this class of problems, in which interfacial phenomena tightly interact with the shape and dynamics of the surface, we develop a general continuum mechanics and computational framework for fluid deformable surfaces. The dual solid–fluid nature of fluid deformable surfaces challenges classical Lagrangian or Eulerian descriptions of deforming bodies. Here, we extend the notion of arbitrarily Lagrangian–Eulerian (ALE) formulations, well-established for bulk media, to deforming surfaces. To systematically develop models for fluid deformable surfaces, which consistently treat all couplings between fields and geometry, we follow a nonlinear Onsager formalism according to which the dynamics minimizes a Rayleighian functional where dissipation, power input and energy release rate compete. Finally, we propose new computational methods, which build on Onsager’s formalism and our ALE formulation, to deal with the resulting stiff system of higher-order partial differential equations. We apply our theoretical and computational methodology to classical models for lipid bilayers and the cell cortex. The methods developed here allow us to formulate/simulate these models in their full three-dimensional generality, accounting for finite curvatures and finite shape changes.

Keywords: Capsule/cell dynamics, Computational methods, Membranes

Checa, M., Millan-Solsona, R., Gomila, G., (2019). Frequency-dependent force between ac-voltage-biased plates in electrolyte solutions Physical Review E 100, (2), 022604

We analyze the frequency dependence of the force between ac-voltage-biased plates in electrolyte solutions. To this end we solve analytically the Poisson-Nernst-Planck transport model in the dilute concentration and low voltage regime for a 1:1 symmetric electrolyte with blocking electrodes under a dc+ac applied voltage. The total force, which is the resultant of the electric and osmotic forces, shows a complex dependence on plate separation, frequency, ion concentration, and compact layer properties, different from that predicted from electrostatic current models or equivalent circuit models, due to the relevance of the osmotic force contribution in almost the whole range of frequencies. For the total dc force, we show that it decays at fixed ion concentration, linearly with plate separation for separations larger than a few times the Debye screening length. This linear dependence is due to the assumption about the conservation of the number of ions in the system. Moreover, the 1ω and 2ω ac harmonics of the total force show a broad peak at intermediate frequencies; it is centered at about the inverse of the charging time of the double layer capacitance, and covers the frequency range between the inverse of the diffusion time and the inverse of the electrolyte dielectric relaxation time. Finally, the 1ω ac harmonic component attains its high frequency asymptotic value at frequencies much higher than the inverse of the electrolyte dielectric relaxation time due to the very slow relaxation of the osmotic 1ω harmonic component at high frequencies. The derived analytical expressions for the total force remain valid up to voltages of the order of the thermal voltage, as has been assessed by means of numerical calculations. The numerical calculations are also used to explore the onset of higher force harmonics for larger applied voltages. Understanding the frequency dependence of the force acting on voltage-biased plates in electrolyte solutions can be of relevance for electrical actuation strategies in microelectromechanical systems and for the interpretation of some emerging electric scanning probe force microscopy techniques operating in electrolyte solutions.

Keywords: Electrochemistry, Statistical physics

Lozano, Helena, Fabregas, Rene, Blanco, Núria, Millán, Rubén, Torrents, Eduard, Fumagalli, Laura, Gomila, Gabriel, (2018). Dielectric constant of flagellin proteins measured by scanning dielectric microscopy Nanoscale 10, 19188-19194

The dielectric constant of flagellin proteins in flagellar bacterial filaments ~10-20 nm in diameter is measured using Scanning Dielectric Microscopy. We obtain for two different bacterial species (Shewanella oneidensis MR-1 and Pseudo-monas aeruginosa PAO1) similar relative dielectric constant values εSo = 4.3 ± 0.6 and εPa = 4.5 ± 0.7, respectively, despite their different structure and aminoacid sequence. Present results show the applicability of Scanning Dielectric Microscopy to nanoscale filamentous protein complexes, and to general 3D macromolecular protein geometries, thus opening new avenues to study the relationship between dielectric response and protein structure and function.

Van Der Hofstadt, Marc, Fabregas, Rene, Millan, Ruben, Juarez, Antonio, Fumagalli, Laura, Gomila, Gabriel, (2016). Internal hydration properties of single bacterial endospores probed by electrostatic force microscopy ACS Nano 10, (12), 11327–11336

We show that the internal hydration properties of single Bacillus cereus endospores in air under different relative humidity (RH) conditions can be determined through the measurement of its electric permittivity by means of quantitative electrostatic force microscopy (EFM). We show that an increase in the RH from 0% to 80% induces a large increase in the equivalent homogeneous relative electric permittivity of the bacterial endospores, from ~4 up to ~17, accompanied only by a small increase in the endospore height, of just a few nanometers. These results correlate the increase of the moisture content of the endospore with the corresponding increase of environmental RH. 3D finite element numerical calculations, which include the internal structure of the endospores, indicate that the moisture is mainly accumulated in the external layers of the endospore, hence preserving the core of the endospore at low hydration levels. This mechanism is different from what we observe for vegetative bacterial cells of the same species, in which the cell wall at high humid atmospheric conditions is not able to preserve the cytoplasmic region at low hydration levels. These results show the potential of quantitative EFM under environmental humidity control to study the hygroscopic properties of small scale biological (and non-biological) entities and to determine its internal hydration state. A better understanding of nano-hygroscopic properties can be of relevance in the study of essential biological processes and in the design of bio-nanotechnological applications.