Biohybrid Nose-Power of Mosquito’s Olfactory Receptor to detect Cancer!

 With advancements in AI and Computer technology we have been able to replicate our core senses. Developments of smart prosthetic and hearing devices are good examples that can support the statement. Replication of our sense of smell has been a difficult task for researchers. ‘Smell-O-Presence ’ for computers sound strange right? But in a research paper published in Science Advances researchers were able to turn this impossibility into a possibility by creating a Biohybrid Nose that uses olfactory receptors of mosquitoes for sensing VOC.

 

Why Olfactory Receptors of Mosquitoes?

Probably a first question that might have struck your brain…

We humans are not ‘master of smell’ in animal kingdom. Therefore rather than going to humans researchers turned their attention towards yellow fever mosquito (yike). These mosquitoes have great sense of smell due to their highly sensitive odor receptors. Instead they have a separate component that can amplify the electrical signal biologically. It is also easy for the researchers to collect the strains of yike and research on them.

 

What is VOC and VOC sensor?

VOC stands for Volatile Organic Compounds. These compounds are characterized by high vapor pressure i.e. low boiling point. The harmful effects of VOC’s on humans depend upon its time of exposure. High exposure to VOC can even cause cancer as a long term effect.




As the name suggests VOC sensors are used to detect the presence of volatile organic compounds. Current VOC sensors that have been designed using artificial material have sensitivity which is much less as compared to the sensitivity of living organisms.

So what if we use olfactory receptors of living organisms in VOC sensors instead of artificial material so that we can fight against cancer and many other fatal diseases at an earlier stage?

This idea led to the development of biohybrid sensor by using mosquito’s olfactory receptors!

As now you know much of the basic idea we can proceed further with the actual experiment of biohybrid sensor and its power to save many cancer patients.

Olfactory sensors or VOC sensors based on the olfactory receptors:

Basically, in simple words, olfactory receptors are smell receptors; proteins which can bind odour molecules that play essential role in the olfaction process i.e., sense of smell.

Generally, the biohybrid sensors based on the olfactory receptors (here abbreviated as ORs) are of two types:

1)    Cell-based:

The electrical signals or changes in the fluorescence intensity is generated as the intracellular reactions occur and hence the odour signals are detected based on the reactions. There are some problems involved due to complexity of living cells such as variability, dependency on cell conditions and environmental changes.

2)    Cell- free:

Here, the ORs are regenerated in the lipid bilayer, a response of the receptors is analysed and by virtue of electrophysiological recordings and the results are generated at the molecular level. These sensors eliminate the complex interactions and unnecessary biochemical reactions during the sensing process hence have improved reproducibility, quantification, and storage stability in comparison with cell-based sensors.

 

In one experimental study, a VOC sensor of cell-free type was developed which was combined with the gas flow system which helps in achieving high detection probabilities at low VOC concentration. A lipid bilayer forming droplet is placed on the hydrophobic microslits that form the gas flow channels underneath the droplet. Due to continuous gas flow and the shear stresses at the liquid-gas interface assist the transport of VOCs to the ORs by easy convection into the droplet. It was observed that the detection probability can be enhanced by designing the array of lipid bilayers. This sensor involves the Olfactory receptors and OR co-receptor as the sensing element which forms a ligand gated ion channel and carry out the detection of odour using electrophysiological recordings. 

This experiment gives the basic idea of VOC sensor or olfactory sensor having olfactory receptors of living organisms.




 

How do biohybrid sensors with ORs help in the diagnosis of cancer?

It is believed that the analysis of humans’ breath for specific biomarkers gives effective disease diagnosis results as it is easily sampled and cost effective. A possible biomarker for cancer in the human body is OCTENOL. Hence detection of which from human breath is carried out to diagnose cancer.

The basic process is demonstrated in the following figure:


The human breath is collected by a Tedlar bag and transferred to the sensor device through the inhalation tube. This biohybrid olfactory sensor has yellow fever mosquito (Aedes aegypti) Olfactory Receptor. There is a regulator to maintain the constant flow rate (0.2L/min). When the human breath enters the device, 16 current signals are generated. As the human breath constitutes 3000 different metabolites, samples without octenol produced almost flat curves fig B, while breath samples with octenol present, generated clear open signals as in fig C, D. 

This biohybrid ‘nose’ is highly sensitive and selective as it can detect the level of octenol in the range of parts per billion (ppb) and even 0.5 ppb of octenol which is not even possible using normal gas chromatography hence can diagnose the cancer easily and effectively.

Applications of ‘biohybrid nose’ at present and in future:

1.    For detecting early stages of diseases,

2.    In biological odorant sensing,

3.    In breath diagnosis systems,

4.    In environmental monitoring,

5.    To screen toxic chemicals in contaminated wastelands, etc.

Yet the technology is under development stage as more sophisticated AI technology is still under development for this sensor. For now, it can sense only one odour at a time, but it is believed that one day, by mixing and matching various odour receptors this biohybrid nose can outsmart human nose. 

 

Credits: Vanshita Jain (SY Computer, 112003052), 

              Madhura Mahamuni (TY Metallurgy, 111911024 )

               (Team Tech Tuesday)

 References:

1.    https://www.science.org/doi/10.1126/sciadv.abd2013

TETSUYA YAMADA, HIROTAKA SUGIURA, HISATOSHI MIMURA, KOKI KAMIYA, TOSHIHISA OSAKI AND SHOJI TAKEUCHI. 2021. Highly sensitive VOC detectors using insect olfactory receptors reconstituted into lipid bilayers. SCIENCE ADVANCES. Vol 7, Issue 3.

(https://doi.org/10.1126/sciadv.abd2013)

2.    https://singularityhub.com/2021/01/26/scientists-made-a-biohybrid-nose-using-cells-from-mosquitoes/

3.    https://www.britannica.com/science/olfactory-receptor

4.    https://www.pennmedicine.org/news/news-releases/2021/june/electronic-nose-accurately-sniffs-out-hard-to-detect-cancers

5.    http://flickr.com/


  NOTE:-

This blog is meant for Educational Purpose only .We do not own any Copyrights related to images and information , all the rights goes to their respective owners . The sole purpose of this blog is to Educate, Inspire, Empower and to create awareness in the viewers. The usage is non-commercial(Not For Profit) and we do not make any money from it.


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