As stated in the previous chapter, Wolfgang Göpel wrote, “Bioelectronics is aimed at the direct coupling of biomolecular function units of high molecular weight and extremely complicated molecular structure with electronic or optical transducer devices” [1]. The statement emphasizes two key points: the “direct coupling” and the “high molecular weight”. This leads us now to develop bioelectronic circuitries by moving from building blocks, or molecular components, that involve high-molecular-weight biological molecules (typically proteins) by providing electrical contact at the nanoscale, in order to address direct coupling. The first problem to solve is therefore that of a nanoscale electrical contact.

During the last 15 years, several fabrication methods have been proposed to obtain a nanogap [2], based on the original work of Morpurgo et al. [3]. Among the possible solutions, a very effective strategy is to create an extremely tiny disconnection along a conducting wire in order to accommodate a biological molecule in between (Figure 2.1). The idea is to erode the electrical wire laterally in order to reduce its size until one obtains a nanoscale conductor that becomes disconnected at a certain stage of the erosion. Morpurgo et al. [3] demonstrated that the wire’s conductivity becomes quantized in the moments immediately before the electrical connection breaks because the wavelength of the Schrödinger function associated with electrons becomes comparable to the lateral size of the wire. We can therefore control the breaking of the connection by monitoring this quantum current. Now, we can obtain a nanoscale interruption in the wire by stopping the erosion immediately after the appearance of quantum states. If electrochemical etching provides the erosion, then it is easy to control the process by means of a feedback system driven by the wire conductivity. Experimental results show that gaps can be obtained in the interrupted wire with sizes down to 20 nm [3]. Considering now the typical size of metalloproteins, close to 5 nm [4], or of antibodies, up to 15 nm [5], we can see that gaps of 20 nm are too large for quantum tunneling from the Fermi level in the metal to the LUMO (lowest unoccupied molecular orbital) in the protein [6].