Biosensors based on olfactory receptors to decipher the human sense of smell

The human olfactory system discriminates between thousands of odours by interacting specifically with olfactory receptors on sensory neurons. Each receptor can detect several odorants at different intensities, and the same odorant can activate more than one receptor. This complex combination of signals generates our olfactory perception.

The biological importance of olfaction, which enables us to forage, interact socially and detect danger, has driven the development of olfactory sensors with various industrial applications. Although olfactory receptor-based sensors are very sensitive, detecting concentrations down to the femtomolar level - parts per thousand trillion - they have one limitation: they cannot accurately distinguish between the different odours that trigger them.

In this context, a recent study led by the Institute forBioengineering of Catalonia (IBEC) and the Centre for Biomedical Research Network on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), in collaboration with the Centre des Sciences Du Goût et de l'Alimentation and the Institut de Chimie de Nice, has developed an innovative method to distinguish between odours that activate the same receptor. This method is based on the detection of small electrical changes in the receptor, known as the capacitive response. These changes are proportional to the strength with which the odorant binds to the receptor, mimicking the physiological response to an odour.

“We have seen that when the receptor comes into contact with one of the compounds, there is a change in the electrical response that is proportional to the strength with which the compound binds to the receptor. This information helps us to better understand how olfactory recognition works at the molecular level and how this knowledge can be used to design more effective sensors,” explains Anna Lagunas, first author of the study and senior researcher in IBEC's Nanobioengineering group led by Josep Samitier.

This innovation is a step forward in the design of more precise sensors, which could have applications in odour screening or in other technological and industrial fields.

Selective detection of odours

For the experiments, a human olfactory receptor (hOR1A1) was immobilised on a gold surface with an antibody to ensure its orientation and improve the sensitivity of the measurements. The three olfactory substances used (dihydrojasmone and two forms of carvone) are agonists of the receptor, i.e. they are all capable of activating it, giving rise to different odours, which makes it possible to simulate real physiological activations.

The study, which also involved IBEC's Nanoprobes and Nanoswitches group led by Pau Gorostiza, explains that the sensor's increased ability to identify substances is due, among other things, to the specific electrical response of the receptor, linked to an intrinsic property called the dipole moment, which varies in the presence of the odorant. The dipole moment is a measure of the distribution of electrical charges within a molecule. In this case, changes in the dipole moment of the receptor when it binds to an odour molecule are key to detecting it.