Cell-Based Sensing

Nose on a Chip

I am collaborating with Pamela Abshire (ECE), Ricardo Araneda (Department of Biology), Abhinav Shrivastava (Computer Science), and David Tomblin (Science, Technology, and Society) to develop an "e-nose" for odorant identification.

In earlier work, we showed that olfactory sensory neurons cultured on integrated circuit chips can detect odorants. We are currently working with an engineered insect cell line, in collaboration with researchers at NARO in Tsukuba, Japan, that gives a fluorescence response to odorant binding.

Biological olfactory sensors have, as yet, no equal in human-made devices.

1. The binding event is amplified in the cell.
   Odorant binding activates a biochemical amplification that results in an action potential (AP). In mammals, OSNs contain an olfactory-specific G-protein (Golf), tens of which are activated upon odorant binding. In turn, this activates adenylate cyclase, which catalyzes the conversion of adenosine triphosphate (ATP) into a neurotransmitter, cyclic AMP (cAMP). A single activated enzyme can convert a large number of ATPs (1000/second). The increase in cAMP opens ion channels that permit Na+ and Ca2+ to enter the cell, depolarizing the neuron and triggering an AP, which can readily be detected extracellularly.
2. Use of OSNs provides a large dynamic range due to adaptation.
   OSNs “adapt” and reduce the rate of action potentials in response to the continued presence of an odorant. Adaptation occurs because of: (1) increased Ca2+ binding by the protein calmodulin, decreasing the sensitivity of the channel to cAMP; and (2) the extrusion of Ca2+ through the activation of Na+/Ca2+ exchange proteins that reduce the amplitude of the receptor potential.
3. The cells provide the “infrastructure” for maintaining the receptors.
   Cells regulate and repair themselves to maintain normal function (homeostasis).
4. OSNs produce an electrical signal (action potential) upon odorant binding.
   These signal can be detected extra-cellularly, and the number of APs is correlated with the odorant concentration.
5. Cells can be engineered to express odorant receptors (ORs) and to give a fluorescence signal upon odorant binding.
   These signal can also be detected extra-cellularly, with the fluorescece intensity correlated with the odorant concentration.