Abstract

This paper describes a method to estimate the direction from which the signal molecule reaches the sensor by using living cells. In this context, biohybrid sensors that utilize a sophisticated sensing system of cells can potentially offer high levels of chemical-detection sensitivity and selectivity. However, biohybrid-sensor-based chemical-source-direction estimation has not received research attention because the cellular response to chemicals has not been examined in the context of directional information. In our approach, we fabricated a device that can limit the interface between the cell-laden hydrogel and the chemical solution of interest to enhance the time difference over which the chemical solution reaches the cells. Chemical detection by cells that express specific receptors is reflected as the fluorescence of the calcium indicator within the cells. Our device has eight chambers that each house 3D cell-laden collagen hydrogels facing circularly outward. The device also works as a cover to prevent chemicals from permeating the hydrogel from above. In our study, by observing the time course of the fluorescence emission of each chamber, we were able to successfully estimate the chemical-source direction within an error range of 7–13°. Our results suggest that a combination of microstructure devices embedded with living cells can be used to exploit cell functionalities to yield chemical-source directional information.

Highlights

  • The detection and identification of chemicals in the environment are essential in many situations, in the context of medical tests and field monitoring [1,2,3]; in medicine, many chemicals are investigated as markers for diagnostics, and as regards field testing, industrial sites are monitored regularly for chemical leaks

  • We developed a cell-based biohybrid sensor device to estimate the chemical-source direction by observing the reaction of HEK293T cells expressing muscarinic acetylcholine receptors to muscarine

  • By limiting the number of openings to each chamber to the outward-facing side and limiting the chemical-solution-interface of the cell-laden hydrogel, we were able to focus on the difference in arrival time of the chemical solution

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Summary

Introduction

The detection and identification of chemicals in the environment are essential in many situations, in the context of medical tests and field monitoring [1,2,3]; in medicine, many chemicals are investigated as markers for diagnostics, and as regards field testing, industrial sites are monitored regularly for chemical leaks These applications require both the ability to distinguish between different chemicals and the estimation of the direction of origin of the chemical source. The currently used chemical sensors such as surface plasmon resonance (SPR) [4, 5] and quartz crystal microbalance (QCM) sensors [6, 7] offer highly sensitive detection capabilities. There have been significant advances in the fabrication of the sensitive membranes, it is still a challenge to detect chemicals with similar chemical properties with these membranes

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