Highly Efficient Detector of the Neurotransmitter ACh and AChE Inhibitors
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1009-U08-04
Highly Efficient Detector of the Neurotransmitter ACh and AChE Inhibitors Ilya Goykhman1,2, Nina Korbakov1, Carmen Bartic3, Gustaaf Borghs3, Micha E. Spira4, Josef Shappir2, and Shlomo Yitzchaik1 1 Department of Analytical and Inorganic Chemistry, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel 2 School of Engineering, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel 3 IMEC, Kapeldreef 75, Leuven, B-3001, Belgium 4 Department of Neurobiology, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel ABSTRACT Among the variety of applications for biosensors one of the exciting frontiers is to utilize those devices as post-synaptic sensing elements in chemical coupling between neurons and solid-state systems. The first necessary step to attain this challenge is to realize highly efficient detector for neurotransmitter acetylcholine (ACh). Herein, we demonstrate that the combination of floating gate configuration of ion-sensitive field effect transistor (ISFET) together with diluted covalent anchoring of enzyme acetylcholinesterase (AChE) onto device sensing area reveals a remarkable improvement of a four orders of magnitude in dose response to ACh. This high range sensitivity in addition to the benefits of peculiar microelectronic design show, that the presented hybrid provides a competent platform for assembly of artificial chemical synapse junction. Furthermore, our system exhibits clear response to eserine, a competitive inhibitor of AChE, and therefore it can be implemented as an effective sensor of pharmacological reagents, organophosphates, and nerve gases as well. INTRODUCTION Modern biosensor technology introduces high selectivity and sensitivity for biologically active materials, when among the variety of concepts, the integration of ISFETs and bio-compounds is one of the most attractive approaches. The typical configuration of such hybrid devices involves a receptor immobilization onto exposed gate dielectric of ISFET structure, so that the specific bio-recognition processes and particular molecular interactions can be successfully transduced into measurable electrical signals [1-3]. The direct contact between electrolyte solution and solid-state structure involves a risk of fast degradation of the electronic system; therefore our device is designed with a floating gate (FG) electrode, where the bio-electronic coupling area is shifted aside from the active transistor. This approach has been previously applied in realization of neuronFET electrical coupling [4] and it offers several important advantages: isolation and protection of active transistor from the ionic solution, possibility to increase sensing area without harming the response time of active transistor, improving of system sensitivity by increasing FG to channel area ratio and uniform modulation of the transistor channel potential.
Acetylcholinesterase (AChE) grafting onto device sensing area allows integration between biological and electronic systems, when in principle such transducer can be constructed
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