Thought Leaders

An Overview and Future Trends in Biomolecular Electronics

Biomolecular Electronics is a branch of nano-science and technology dealing with the investigation and the technological exploitation of electron transport properties in special classes of biomolecules. Albeit it deals with molecules that can donate to or receive electrons, biomolecular electronics has nothing to do with the molecular bases ruling the generation and propagation of electrical signals in neural cells, i.e. the action potential. This very important example of electrical activity pertaining biological matter, depends in fact on ionic currents and involves a well known interplay between protein channels varying their permeability to ions in response to certain stimuli and the dielectric properties of the axon membrane they are embedded in.

Biomolecular electronics, instead, deals with biomolecules which are able to transfer electrons between molecular partners as a result of redox reactions1. These molecules can be redox metalloproteins, proteins bearing redox moieties (e.g. disulfide bonds) or redox cofactors (e.g quinone-based molecules).

It is believed that about 25-30% of the entire proteome is composed by metalloproteins; therefore understanding their behavior, possibly at the single molecule level, represents an extremely relevant enterprise. Furthermore, the physiological functional activity of redox metalloproteins of shuttling electrons between redox partners has been optimized by more than 4 billions years natural evolution and, as such, it results to be extremely effective and appealing for applications.

The scientific activity on biomolecular electronics dates back to the early nineties and has been triggered by the advent of scanning probe microscopes, especially the scanning tunnelling microscope (STM).

Nowadays, the experimental tool of choice for the investigation of electron transport in redox metalloproteins at the single molecule level is an evolution of STM that can be operated in a four-electrode electrochemical cell: the electrochemical scanning tunnelling microscope (ECSTM)2. It features the possibility of measuring tunnelling currents in physiologic-like, salty aqueous solution through molecular adsorbates on atomically flat, conductive substrates. Therefore, at variance with the well known STM, it makes use of insulated tips and of a bipotentiostat that can drive independently the potential of the metal substrate and the tip, thus preventing faradic currents to take place at both working electrodes (tip and substrate). The result is a microscope which provides spectroscopic-like images of molecular adsorbates. A generic ECSTM setup is depicted in figure 1.

Scheme of an ECSTM. The inset shows an insulated ECSTM probe.
Figure 1. Scheme of an ECSTM. The inset shows an insulated ECSTM probe.

A prototypical redox metalloprotein that has been widely investigated by ECSTM is azurin from Pseudomonas aeruginosa, a molecule belonging to the family of the blue copper proteins, as its intense blue colour reveals. This redox protein shuttles electrons between proteinaceous partners by changing reversibly the oxidation state of a copper atom in its active site (Cu2+⇔Cu1+). Furthermore, its structure is characterized by an exposed disulfide bridge (Cys3-Cys26) which turns out to be extremely useful for anchoring the molecule on an atomically flat gold substrate, figure 2.

The 3d structure of azurin from Pseudomonas aeruginosa. Structural information from PDB file 1E5Y.
Figure 2. The 3d structure of azurin from Pseudomonas aeruginosa. Structural information from PDB file 1E5Y.

ECSTM investigation of azurin reveals firstly a substrate potential dependent contrast in constant current images3; the appearance of molecular features in the images results from the proper alignment of the Fermi levels of substrate and tip, as determined by the bipotentiostatic control, with respect to the molecular redox levels (the "density of oxidized or reduced levels"). Furthermore, ECSTM studies show the possibility of distinguishing between molecules, identical in their structure but bearing different metal ions in their active site (eg. Cu vs Zn)4. This possibility is enabled by the radically different redox potential of the two ions. From an applied standpoint, the reported behavior qualifies azurin as a molecular electronic switch and enables solid state electronic applications5.

Direct access to tunnelling current enables also a detailed analysis of the electron transport mechanisms involved in the phenomenon. Implementing a "change of perspective" one can immobilize azurin on a gold ECSTM tip, achieving the advantages of i) avoiding to track the molecules adsorbed on the substrate; ii) measuring directly the tunnelling current by switching the feedback system off, once the current set point has been established, while sweeping tip voltage. Under these conditions, it is possible to extract data that allow one to elucidate the mechanism underlying electron transport as a two step electron transfer with partial molecular relaxation6. A this point it is worth noting that the realized setup configures a single protein transistor with an electrochemical gate7. Indeed, it is physically equivalent to a single particle transistor typical of nanoelectronics: in the latter the gating is provided by capacitive coupling between a (back) gate and the electronic level of the dot, whereas, in the former, there is a sort of "diffused gating" brought about by the electrochemical control of tip and substrate Fermi levels.

The demonstration of a single metalloprotein wet biotransistor, as well as similar findings on other redox molecules8, can in principle pave the way to the exploitation of the switching behaviour of suitable biomolecules for implementing nanoelectronic devices operating in a wet environment.

In spite this configures a suggestive scenario, it is questionable whether such kind of approach will be ever competitive with solid state nanoelectronics. Indeed, we believe its relevance in applications should be sought in a different context. The novelty of the described findings stands in that they establish the concept of "electrically controlled biological reactions". This concept encompasses not only redox reactions and is not limited to redox proteins; rather, it includes also electrically-induced conformational changes in charged biomolecules and extends to other kinds of proteins such as enzymes, antibodies, redox cofactors as they are involved in many diverse biological phenomena. This quite suggestive perspective aims to gather the most advanced technology that Mankind have ever developed (Electronics) with the most sophisticated organization level of the matter that Nature has so far produced: the biological matter.

Exemplifications of the aforementioned concept span from modulation of the binding affinity of antibodies for the corresponding antigens by electrical induced conformational changes, to modulation of gene expression profile via tuning the conformation of redox enzymes involved in the control of gene expression. All of these examples are currently object of intense investigation and represent the most proming future trends in Biomolecular Electronics.


  1. A. Alessandrini, P. Facci "Metalloprotein Electronics" in CRC Handbook in Nano- and Molecular Electronics Ed. S. Lyshevsky, Boca Raton, 14, 1-47, (2007).
  2. Andrea Alessandrini, & Paolo Facci "Electrochemically Assisted Scanning Probe Microscopy: a Powerful Tool in Nano(Bio)Science" in Biophysical Aspects of Nanotechnology, V. Erokhin, M.K. Ram, O. Yavuz Eds., Elsevier, 2007.
  3. P. Facci, D. Alliata, S. Cannistraro "Potential-Induced Resonant Tunneling through a Redox Metalloprotein Probed by Electrochemical Scanning Probe Microscopy", Ultramicroscopy, 89(4), 291-298, (2001).
  4. A. Alessandrini, M. Gerunda, G. Canters, M. Ph. Verbeet, P. Facci "Electron Tunneling through Azurin is Mediated by the Active Site Cu Ion", Chem. Phys. Lett., 376/5-6 pp. 625-630, (2003).
  5. R. Rinaldi, A. Biasco, G. Maruccio, R. Cingolani, D. Alliata, L. Andolfi, P. Facci, F. De Rienzo, R. Di Felice, E. Molinari "Solid-State Molecular Rectifier Based on Self-Organized Metalloproteins", Adv. Mater., 14, 1449-1453, (2002); R. Rinaldi, A Biasco, G. Maruccio, R. Cingolani, D. Alliata, L. Andolfi, P. Facci, F. De Rienzo, R. Di Felice, E. Molinari, M. Verbeet and G. Canters, "Electronic rectification in protein devices", Appl. Phys. Lett., 82, 472 (2003).
  6. A. Alessandrini, S. Corni, P. Facci "Unraveling single metalloprotein electron transfer by scanning probe techniques" Phys. Chem. Chem. Phys., 8, 4383-4397 (2006).
  7. A. Alessandrini, M. Salerno, S. Frabboni, P. Facci "Single-metalloprotein wet biotransistor" Appl. Phys. Lett., 86, 133902, (2005).
  8. P. Petrangolini, A. Alessandrini, L. Berti, P. Facci "An Electrochemical Scanning Tunneling Microscopy study of 2-(6-mercaptoalkyl)hydroquinone molecules on Au (111)", J. Am. Chem. Soc., 2010, 132, 7445–7453.

Disclaimer: The views expressed here are those of the interviewee and do not necessarily represent the views of Limited (T/A) AZoNetwork, the owner and operator of this website. This disclaimer forms part of the Terms and Conditions of use of this website.


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Facci, Paolo. (2019, July 15). An Overview and Future Trends in Biomolecular Electronics. AZoNano. Retrieved on December 02, 2023 from

  • MLA

    Facci, Paolo. "An Overview and Future Trends in Biomolecular Electronics". AZoNano. 02 December 2023. <>.

  • Chicago

    Facci, Paolo. "An Overview and Future Trends in Biomolecular Electronics". AZoNano. (accessed December 02, 2023).

  • Harvard

    Facci, Paolo. 2019. An Overview and Future Trends in Biomolecular Electronics. AZoNano, viewed 02 December 2023,

Tell Us What You Think

Do you have a review, update or anything you would like to add to this article?

Leave your feedback
Your comment type