Single Osteoblast Chemical Sensor via Non-invasive Bio-Electronic Interface
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Single Osteoblast Chemical Sensor via Non-invasive Bio-Electronic Interface Mo Yang, Xuan Zhang, Bonnie Kohr, Andre Morgan and Cengiz S Ozkan Mechanical Engineering Department, University of California, Riverside, CA 92521 ABSTRACT The broad-spectrum sensitivity of cell based biosensors offers the capability for detecting known and unknown chemical/biological agents. One cellular parameter that is often measured is the extracellular potential of electrically active cells. Membrane excitability in osteoblasts plays a key role in modulating the electrical activity in the presence of chemical agents. However, the complexity of this signal makes interpretation of the cellular response to a chemical agent difficult to interpret. By analyzing shifts in the signal’s power spectrum, it is possible to determine a frequency spectrum also known as Signature Pattern Vectors (SPV) specific to a chemical. We used a 5x5 multiple microelectrode array system to spatially position osteoblast cells, by using a gradient AC field. Fast Fourier Transformation (FFT) analyses were used to extract information pertaining to the frequency of firing from the extracellular potential. INTRODUCTION Techniques to develop highly sensitive biosensors are largely dependant upon the properties of the material and its associated interactions1-3. Current biosensor technologies encompass antibody-antigen interactions4, hormone-receptor interactions5, 6, and nucleic acid based assays7-9. These sensors are useful in narrow band applications requiring high specificity for agent identification10, 11. Mammalian cells have excitable cell membranes that function as novel sensing platforms by producing a variation in the extracellular potential based on the chemical stimulus12. Here we report a method of developing single cell based sensors by integrating the biological tool of dielectrophoresis13 with the micro fabrication technology14, 15. We display its ability to detect a large number of chemical agents, reject false alarms, characterize the chemical agent functionality and determine the associated sensitivity limit, and the physiological response in terms of the calcium transients for each specific chemical agent that produces synergistic effects on humans. We finally demonstrate the capability of a single cell based sensor to identify general chemical agents in cascade. Biosensor technology is the driving force in the development of biochips for the detection of environmental pollutants16, toxins17, biological and chemical pollutants18. A novel challenge is the development of effective bio-sensors which will change the existing axiom of “detect -to-treat” to “detect -to-warn”. Cell based biosensors offer the two fold opportunity of detecting a broad spectrum of known/unknown chemical agents and determining the impact on human performance by monitoring the variations in the physiological activity caused by the exposure to environmental threats19-21. Extracellular potential measurement from the cell membrane is considered a reliable indicator for the
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