Harnessing insect olfactory neural circuits for detecting and discriminating human cancers

Alexander Farnum; Michael Parnas; Ehsanul Hoque Apu; Elyssa Cox; Noël Lefevre; Christopher H Contag; Debajit Saha

doi:10.1016/j.bios.2022.114814

Harnessing insect olfactory neural circuits for detecting and discriminating human cancers

Biosens Bioelectron. 2023 Jan 1:219:114814. doi: 10.1016/j.bios.2022.114814. Epub 2022 Oct 15.

Authors

Alexander Farnum¹, Michael Parnas¹, Ehsanul Hoque Apu², Elyssa Cox¹, Noël Lefevre¹, Christopher H Contag³, Debajit Saha⁴

Affiliations

¹ Department of Biomedical Engineering and the Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
² Department of Biomedical Engineering and the Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Division of Hematology and Oncology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, 48108, USA.
³ Department of Biomedical Engineering and the Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA.
⁴ Department of Biomedical Engineering and the Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA. Electronic address: sahadeb3@msu.edu.

PMID: 36327558
DOI: 10.1016/j.bios.2022.114814

Abstract

There is overwhelming evidence that presence of cancer alters cellular metabolic processes, and these changes are manifested in emitted volatile organic compound (VOC) compositions of cancer cells. Here, we take a novel forward engineering approach by developing an insect olfactory neural circuit-based VOC sensor for cancer detection. We obtained oral cancer cell culture VOC-evoked extracellular neural responses from in vivo insect (locust) antennal lobe neurons. We employed biological neural computations of the antennal lobe circuitry for generating spatiotemporal neuronal response templates corresponding to each cell culture VOC mixture, and employed these neuronal templates to distinguish oral cancer cell lines (SAS, Ca9-22, and HSC-3) vs. a non-cancer cell line (HaCaT). Our results demonstrate that three different human oral cancers can be robustly distinguished from each other and from a non-cancer oral cell line. By using high-dimensional population neuronal response analysis and leave-one-trial-out methodology, our approach yielded high classification success for each cell line tested. Our analyses achieved 76-100% success in identifying cell lines by using the population neural response (n = 194) collected for the entire duration of the cell culture study. We also demonstrate this cancer detection technique can distinguish between different types of oral cancers and non-cancer at different time-matched points of growth. This brain-based cancer detection approach is fast as it can differentiate between VOC mixtures within 250 ms of stimulus onset. Our brain-based cancer detection system comprises a novel VOC sensing methodology that incorporates entire biological chemosensory arrays, biological signal transduction, and neuronal computations in a form of a forward-engineered technology for cancer VOC detection.