Nanoscale bioelectrical characterization


Gabriel Gomila Lluch | Group Leader
Ricardo Hidalgo Gonzalez | Postdoctoral Researcher
Lázaro René Izquierdo Fábregas | Postdoctoral Researcher
Adrica Kyndiah | Postdoctoral Researcher
Martí Checa Nualart | PhD Student
Martina Di Muzio | PhD Student
Helena Lozano Caballero | PhD Student
Rubén Millán Solsona | Laboratory Technician

About

The main goal of the Nanoscale Bioelectrical Characterization group is to develop new experimental setups based on atomic force microscopy and theoretical frameworks enabling the access to the electrical properties of biological systems at the nanoscale (including biomembranes, single viruses, single bacteria cells and eukaryotic cells).

Our main objective is to contribute to develop new label-free biological nanoscale characterization methods and new electronic biosensors.

Above right: top row: Topographic images of a single bacterial endospore measured by Atomic Force Microscopy at different environmental relative humidity conditions. Bottom Row: Dielectric images of the same bacterial endospore measured by Electrostatic Force Microscopy under the same relative humidity conditions. While the topography of the bacterial endospore remains almost unaltered when modifying the environmental relative humidity, the dielectric response changes dramatically. From these type of measurements, the internal hydration properties of a single endospore can be obtained.

During 2016 we have determined, for the first time, the electromagnetic properties of single bacteria cells in the high frequency range (> GHz) with the use of the Scanning Microwave Microscope and of specific 3D numerical simulation models. We showed that with this approach one can detect the presence of small-scale nanostructures inside microorganisms, providing endless applications in the label-free imaging of single bacterial cells at high spatial resolution.

On the other side, we have probed the internal hydration properties of single bacterial endospores by means of Electrostatic Force Microscopy. Endospores are recognized as the hardiest form of life on Earth, and one of the reasons for this, is that they handle changes in environmental relative humidity in a very smart way.

Left: Atomic Force Microscopy topographic image of embryonic mouse cortical neurons fixed with paraformaldehyde and imaged in air in intermittent contact mode (sample provided by the group of Prof. J. A. del Rio).

We have shown in a label-free way that the endospores are able to preserve their core, where DNA is located, under low hydration conditions, what is key to understand the endospore’s extraordinary survival abilities. On the methodological aspects, we have continued our efforts towards providing a simple interpretation to Electrostatic Force Microscopy and Scanning Microwave Microscopy images of highly non-planar samples, such as single bacterial or eukaryotic cells, for which we have developed a method to remove topographic cross-talk effects from the images.

Finally, we have also optimized sample preparation and imaging methods to image and study electrically excitable cells with the Atomic Force Microscope, such as neurons.

Right: Electrical potential distribution corresponding to the electric interaction between a voltage biased sharp conducting tip of radius 250 nm and a single bacterial cell. The bacterial cell is represented as a 3D ellipsoid structure with uniform electric polarization. From the calculated electric potential distribution the tip-bacteria capacitance can be calculated and compared to experimental measurements obtained with the Scanning Microwave Microscope, in order to determine the electric permittivity of a single bacteria cell at GHz frequencies.

News/Jobs

Training the next generation of advanced microscopy experts
20/01/17

The Nanoscale Biolectrical Characterization group has been awarded EU funding to coordinate a project that aims to train a new generation of researchers in the science and technology of Scanning Probe Microscopes.


Marie Skłodowska-Curie Early Stage Researcher (PhD student) on Nanoscale Tomography based on Electrostatic Force Microscopy
Application Deadline: 28/02/2017

The Nanoscale Biolectrical Characterization group is looking for a Early Stage Researcher (PhD student) to develop his/her PhD thesis project on the development of a novel Nano-tomographic technique based on electrostatic force microscopy.


Marie Skłodowska-Curie Early Stage Researcher (PhD student) on Nanoscale Composition Mapping with Electrostatic Force Microscopy
Application Deadline: 28/02/2017

The Nanoscale Biolectrical Characterization group is looking for a Early Stage Researcher (PhD student) to develop his/her PhD thesis project on the label-free mapping of biological membranes’ composition with nanoscale spatial resolution.


Using EFM to probe the secrets of bacterial endospore survival strategies
01/12/16

An IBEC group has demonstrated, for the first time, that the hydration properties of a single bacterial endospore in varying environmental relative humidity can be determined with high accuracy and reproducibility, and in a non-destructive way, shedding new light on endospore survival strategies.


Microwave electromagnetic properties of single bacterial cells measured for the first time
17/12/15

Researchers at IBEC and their collaborators from the Johannes Kepler University of Linz, The University of Manchester and the company Keysight Technologies have now achieved an elusive goal: to measure the electromagnetic properties of biological materials at the level of a single bacterial cell and at very high frequencies (gigahertz).


Another big step towards understanding the electric properties of the cell
22/10/15

Having measured the electric polarizability of DNA – a fundamental property that directly influences its biological functions – for the first time ever last year, IBEC´s Nanoscale Bioelectrical Characterization group has made a further breakthrough in the understanding of the dielectric properties of cell constituents by measuring the electric polarizability of the main components of the cell membrane – namely lipids, sterols and proteins – with a spatial resolution down to 50nm.


ICREA Academia Award for IBEC group leader
09/02/15

Gabriel Gomila, IBEC group leader and Associate Professor at the UB, has received an ICREA Academia Prize 2014 for excellence in research and capacity for leadership.


IBEC internal collaboration succeeds in measuring bacterial cell response to electrical fields
17/09/14

Two groups working together at IBEC demonstrate the potential of electrical studies of single bacterial cells in a paper published in ACS Nano. Gabriel Gomila’s Nanoscale Bioelectrical Characterization group and that of Antonio Juárez, Microbial Biotechnology and Host-pathogen Interaction, combined their expertise on microscopic electrical measurements and bacteria respectively to come up with a way to study the response to external electrical fields of just a single bacterial cell.


Researchers measure a property of DNA for the first time
18/08/14

The electric polarizability of DNA is a fundamental property that directly influences its biological functions. Despite the importance of this property, however, its measurement has remained elusive so far. In a study published in PNAS today, researchers at Barcelona’s Institute for Bioengineering of Catalonia (IBEC) led by Laura Fumagalli, senior researcher at IBEC and lecturer at the University of Barcelona, and their collaborators at the Institute for Research in Biomedicine (IRB) and at Barcelona Supercomputing Center (BSC), and at Centro Nacional de Biotecnologia (CNB-CSIC) and IMDEA Nanociencia in Madrid, describe how they have found a way to directly measure DNA electric polarizability – represented by its dielectric constant, which indicates how a material reacts to an applied electric field – for the first time ever.


IBEC research on the cover of Nanotechnology
08/07/14

The latest article published by IBEC’s Nanoscale bioelectrical characterization group has made the cover of the journal Nanotechnology.


“Nanomicrowave” cooking up something new
28/02/2013

A new European Marie Curie Initial Training Network involving IBEC’s Nanoscale Bioelectrical Characterization group will attempt to bring research into microwaves – which are extensively used in a host of applications such as telecommunications, microwave ovens and radar – to a whole new level.


‘Fingerprinting’ nanoscale objects and viruses
08/07/2012

Scientists at IBEC in Barcelona have found a way of effectively identifying nanoscale objects and viruses that could offer a breakthrough for biomedical diagnostics, environmental protection and nano-electronics.


Microscope development project for sub-surface imaging at the nanoscale
12/03/2012

IBEC’s Nanoscale Bioelectrical Characterization group, headed by Gabriel Gomila, is a partner in a new EU-funded collaborative project set to develop a new tool for non-destructive 3D nanoscale structural characterization, the Volumetric Scanning Microwave Microscope (VSMM).


New technique to study the electrical activity of the cellular membrane
13/03/2009

Gabriel Gomila and Laura Fumagalli, from the Nanoscale bioelectrical characterization line at IBEC, are two of the authors of the study.

Projects

EU-funded projects
Scanning probe microscopies for nanoscale fast, tomographic and composition imaging (SPM2.0) (2017-2020) Marie Curie Skłodowska European Training Network (MSCA-ITN-ETN) Gabriel Gomila (Project Coordinator)
BIOWIRESENSE Plataforma universal para la detección de biomarcadores basada en nanocables bacterianos conductores (2017-2019) MINECO, Explora Ciencia Gabriel Gomila
National projects
NANOELECTOMOGRAPHY Electrical nanotomography based on scanning probe microscopy for nanomaterials and biological samples (2014-2016) MINECO (TEC2013-48344-C2-1-P) Gabriel Gomila
NANOELECTROPHYS Scanning Electric Force Microscope for Electrophysological Recordings at the Nanoscale
(2016-2019)
MINECO (TEC2016-79156-P) Gabriel Gomila
ICREA Academia Award (2015-2019) Catalan Institution for Research and Advanced Studies (ICREA) / Generalitat de Catalunya Gabriel Gomila
Finished projects
NANOMICROWAVE Microwave Nanotechnology for Semiconductor and Life Sciences (2013-2016) MARIE CURIE – ITN Gabriel Gomila
V-SMMART Nano Volumetric Scanning Microwave Microscopy Analytical and Research Tool for Nanotechnology (2012-2016) NMP – SME Gabriel Gomila
AFM4NanoMed&Bio European network on applications of Atomic Force Microscopy to Nanomedicine and Life Sciences EU COST Action TD1002 Gabriel Gomila (Management Committee Substitute Member)

Publications

Biagi, Maria Chiara, Badino, Giorgio, Fabregas, Rene, Gramse, Georg, Fumagalli, Laura, Gomila, Gabriel, (2017). Direct mapping of the electric permittivity of heterogeneous non-planar thin films at gigahertz frequencies by scanning microwave microscopy Physical Chemistry Chemical Physics 19, 5, 3884-3893

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

Biagi, Maria Chiara, Fabregas, Rene, Gramse, Georg, Van Der Hofstadt, Marc, Juárez, Antonio, Kienberger, Ferry, Fumagalli, Laura, Gomila, Gabriel, (2016). Nanoscale electric permittivity of single bacterial cells at gigahertz frequencies by scanning microwave microscopy ACS Nano 10, 1, 280-288

Van Der Hofstadt, M., Fabregas, R., Biagi, M.C., Fumagalli, L., Gomila, G., (2016). Nanoscale dielectric microscopy of non-planar samples by lift-mode electrostatic force microscopy Nanotechnology 27, 40, 405706

Dols-Perez, Aurora, Gramse, Georg, Calo, Annalisa, Gomila, Gabriel, Fumagalli, Laura, (2015). Nanoscale electric polarizability of ultrathin biolayers on insulator substrates by electrostatic force microscopy Nanoscale 7, 18327-18336

Van Der Hofstadt, M., Hüttener, M., Juárez, A., Gomila, G., (2015). Nanoscale imaging of the growth and division of bacterial cells on planar substrates with the atomic force microscope Ultramicroscopy 154, 29-36

Botaya, Luis, Otero, Jorge, González, Laura, Coromina, Xavier, Gomila, Gabriel, Puig-Vidal, Manel, (2015). Quartz tuning fork-based conductive atomic force microscope with glue-free solid metallic tips Sensors and Actuators A: Physical 232, 259-266

Esteban-Ferrer, Daniel, Edwards, Martin Andrew, Fumagalli, Laura, Juarez, Antonio, Gomila, Gabriel, (2014). Electric polarization properties of single bacteria measured with electrostatic force microscopy ACS Nano 8, 10, 9843–9849

Cuervo, A., Dans, P. D., Carrascosa, J. L., Orozco, M., Gomila, G., Fumagalli, L., (2014). Direct measurement of the dielectric polarization properties of DNA Proceedings of the National Academy of Sciences of the United States of America 111, 35, E3624-E3630

Caló, A., Reguera, D., Oncins, G., Persuy, M. A., Sanz, G., Lobasso, S., Corcelli, A., Pajot-Augy, E., Gomila, G., (2014). Force measurements on natural membrane nanovesicles reveal a composition-independent, high Young's modulus Nanoscale 6, 4, 2275-2285

Dols-Perez, A., Fumagalli, L., Gomila, G., (2014). Structural and nanomechanical effects of cholesterol in binary and ternary spin-coated single lipid bilayers in dry conditions Colloids and Surfaces B: Biointerfaces 116, 295-302

Gramse, G., Kasper, M., Fumagalli, L., Gomila, G., Hinterdorfer, P., Kienberger, F., (2014). Calibrated complex impedance and permittivity measurements with scanning microwave microscopy Nanotechnology 25, 14, 145703 (8)

Gomila, G., Gramse, G., Fumagalli, L., (2014). Finite-size effects and analytical modeling of electrostatic force microscopy applied to dielectric films Nanotechnology 25, 25, 255702 (11)

Fumagalli, L., Edwards, Martin Andrew, Gomila, G., (2014). Quantitative electrostatic force microscopy with sharp silicon tips Nanotechnology 25, 49, 495701 (9)

Castillo-Fernandez, O., Rodriguez-Trujillo, R., Gomila, G., Samitier, J., (2014). High-speed counting and sizing of cells in an impedance flow microcytometer with compact electronic instrumentation Microfluidics and Nanofluidics 16, 1-2, 91-99

Birhane, Y., Otero, J., Pérez-Murano, F., Fumagalli, L., Gomila, G., Bausells, J., (2014). Batch fabrication of insulated conductive scanning probe microscopy probes with reduced capacitive coupling Microelectronic Engineering 119, 44-47

Caballero, D., Fumagalli, L., Teixidor, F., Samitier, J., Errachid, A., (2013). Directing polypyrrole growth by chemical micropatterns: A study of high-throughput well-ordered arrays of conductive 3D microrings Sensors and Actuators B: Chemical 177, 1003-1009

Gramse, G., Dols-Perez, A., Edwards, M. A., Fumagalli, L., Gomila, G., (2013). Nanoscale measurement of the dielectric constant of supported lipid bilayers in aqueous solutions with electrostatic force microscopy Biophysical Journal 104, 6, 1257-1262

Gomila, G., Esteban-Ferrer, D., Fumagalli, L., (2013). Quantification of the dielectric constant of single non-spherical nanoparticles from polarization forces: Eccentricity effects Nanotechnology 24, 50, 505713

Gramse, G., Edwards, M.A., Fumagalli, L., Gomila, G., (2013). Theory of amplitude modulated electrostatic force microscopy for dielectric measurements in liquids at MHz frequencies Nanotechnology 24, 41, 415709

Dols-Perez, A., Sisquella, X., Fumagalli, L., Gomila, G., (2013). Optical visualization of ultrathin mica flakes on semitransparent gold substrates Nanoscale Research Letters 8, 1, 1-5

Fumagalli, Laura, Esteban-Ferrer, Daniel, Cuervo, Ana, Carrascosa, Jose L., Gomila, Gabriel, (2012). Label-free identification of single dielectric nanoparticles and viruses with ultraweak polarization forces Nature Materials Nature Publishing Group 11, 9, 743-826

Calò, A., Sanmartí-Espinal, M., Iavicoli, P., Persuy, M. A., Pajot-Augy, E., Gomila, G., Samitier, J., (2012). Diffusion-controlled deposition of natural nanovesicles containing G-protein coupled receptors for biosensing platforms Soft Matter 8, 46, 11632-11643

Gramse, G., Gomila, G., Fumagalli, L., (2012). Quantifying the dielectric constant of thick insulators by electrostatic force microscopy: effects of the microscopic parts of the probe Nanotechnology 23, 20, 205703

Gramse, G., Edwards, M. A., Fumagalli, L., Gomila, G., (2012). Dynamic electrostatic force microscopy in liquid media Applied Physics Letters 101, 21, 213108

Dols-Perez, Aurora, Fumagalli, Laura, Cohen Simonsen, Adam, Gomila, Gabriel, (2011). Ultrathin spin-coated dioleoylphosphatidylcholine lipid layers in dry conditions: A combined atomic force microscopy and nanomechanical study Langmuir 27, 21, 13165-13172

Fumagalli, L., Gramse, G., Esteban-Ferrer, D., Edwards, M. A., Gomila, G., (2010). Quantifying the dielectric constant of thick insulators using electrostatic force microscopy Applied Physics Letters 96, 18, 183107

Toset, J., Gomila, G., (2010). Three-dimensional manipulation of gold nanoparticles with electro-enhanced capillary forces Applied Physics Letters 96, 4, 043117

Sanmarti, M., Iavicoli, P., Pajot-Augy, E., Gomila, G., Samitier, J., (2010). Human olfactory receptors immobilization on a mixed self assembled monolayer for the development of a bioelectronic nose Procedia Engineering (EUROSENSOR XXIV CONFERENCE) Elsevier Science 5, 786-789

Fumagalli, L., Ferrari, G., Sampietro, M., Gomila, G., (2009). Quantitative nanoscale dielectric microscopy of single-layer supported biomembranes Nano Letters 9, 4, 1604-1608

Gramse, G., Casuso, I., Toset, J., Fumagalli, L., Gomila, G., (2009). Quantitative dielectric constant measurement of thin films by DC electrostatic force microscopy Nanotechnology 20, 39, 395702

Rodriguez-Trujillo, R., Castillo-Fernandez, O., Garrido, M., Arundell, M., Valencia, A., Gomila, G., (2008). High-speed particle detection in a micro-Coulter counter with two-dimensional adjustable aperture Biosensors and Bioelectronics 24, 2, 290-296

Gomila, G., Toset, J., Fumagalli, L., (2008). Nanoscale capacitance microscopy of thin dielectric films Journal of Applied Physics 104, 2, 8

Rodriguez-Trujillo, R., Castillo-Fernandez, O., Arundell, M., Samitier, J., Gomila, G., (2008). Yeast cells detection in a very fast and highly versatile microfabricated cytometer MicroTAS 2008 Chemical and Biological Microsystems Society , 1888-1890

Casuso, I., Pla, M., Gomila, G., Samitier, J., Minic, J., Persuy, M. A., Salesse, R., Pajot-Augy, E., (2008). Immobilization of olfactory receptors onto gold electrodes for electrical biosensor Materials Science & Engineering C Elsevier Science 28, 5-6, 686-691

Equipment

  • Cypher Atomic Force Microscope (Asylum Research)
  • Nanowizard 4 Bio-Atomic Force Microscope (JPK)
  • Cervantes Atomic Force Microscope (Nanotec Electronica)
  • Easy Scan 2 Atomic Force Microscope (Nanosurf)
  • AxioImager A1m Reflection Optical Microscope (Zeiss) equipped with a AxioCam ERc5s (Zeiss)
  • CompactStat portable electrochemical interface and impedance analyzer (Ivium Technologies)
  • 2 eLockIn204 4-phase Lock-In amplifiers (Anfatec)
  • Keithley 6430 sub-femtoAmp remote sourcemeter (Keithley)

Collaborations

  • Dra. Laura Fumagalli
    University of Manchester, United Kingdom
  • Dr. Ferry Kienberger
    Agilent Technologies Austria, Linz, Austria
  • Prof. Marco Sampietro
    Politecnico di Milano, Italy
  • Dr. Jordi Borrell
    University of Barcelona, Spain
  • Prof. Antonio Juárez
    University of Barcelona, Spain
  • Dr. Manel Puig
    University of Barcelona, Spain

Former members

  • Dr. Laura Fumagalli | Senior Researcher
    Now: Lecturer, School of Physics and Astronomy – Condensed Matter Physics, University of Manchester (UK)

  • Dr. Annalisa Calò | Postdoc
    Now: Postdoc, CUNY Advance Science Research Center (USA)
  • Dr. Aurora Dols-Pérez | Postdoc
    Now: Postdoc at the Technical University of Delft (Nederlands)
  • Dr. Martin Edwards | Postdoc
    Now: Research Assistant Professor, University of Utah (USA)
  • Daniel Esteban Ferrer | PhD Student
  • Georg Gramse | PhD Student
    Now: Senior Researcher, Johannes Kepler University of Linz (Austria)
  • Dr. Jordi Otero | Postdoc
    Now: Postdoc, Institute For Bioengineering of Catalonia (IBEC)
  • Marc van der Hofstadt | PhD Student
  • Maria Chiara Biagi | PhD Student

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