Biofuel cell controlled by enzyme logic network — Approaching physiologically regulated devices Tsz Kin Tam, Marcos Pita, Maryna Ornatska, Evgeny Katz ⁎ Department of Chemistry and Biomolecular Science, and NanoBio Laboratory (NABLAB), Clarkson University, Potsdam NY 13699-5810, USA abstract article info Article history: Received 13 December 2008 Received in revised form 6 March 2009 Accepted 6 March 2009 Available online 20 March 2009 Keywords: Biofuel cell Biocomputing Enzyme logic Switchable electrode A “smart” biofuel cell switchable ON and OFF upon application of several chemical signals processed by an enzyme logic network was designed. The biocomputing system performing logic operations on the input signals was composed of four enzymes: alcohol dehydrogenase (ADH), amyloglucosidase (AGS), invertase (INV) and glucose dehydrogenase (GDH). These enzymes were activated by different combinations of chemical input signals: NADH, acetaldehyde, maltose and sucrose. The sequence of biochemical reactions catalyzed by the enzymes models a logic network composed of concatenated AND/OR gates. Upon application of specific “successful” patterns of the chemical input signals, the cascade of biochemical reactions resulted in the formation of gluconic acid, thus producing acidic pH in the solution. This resulted in the activation of a pH-sensitive redox-polymer-modified cathode in the biofuel cell, thus, switching ON the entire cell and dramatically increasing its power output. Application of another chemical signal (urea in the presence of urease) resulted in the return to the initial neutral pH value, when the O 2 -reducing cathode and the entire cell are in the mute state. The reversible activation–inactivation of the biofuel cell was controlled by the enzymatic reactions logically processing a number of chemical input signals applied in different combinations. The studied biofuel cell exemplifies a new kind of bioelectronic device where the bioelectronic function is controlled by a biocomputing system. Such devices will provide a new dimension in bioelectronics and biocomputing benefiting from the integration of both concepts. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Biofuel cells based either on enzyme biocatalyzed reactions or on microbial cells are promising future alternative sources of sustainable electrical energy [1–4]. Miniaturized biofuel cells based on enzyme- catalytic electrodes are considered as implantable sources of energy for various biomedical applications [5–7]. Integration of the miniature biofuel cells with various implantable bioelectronic devices requires their regulated operation controlled by physiological/medical needs. The biofuel cells must be switchable and tunable releasing electrical power on demand. This requires a novel approach to design “smart” biofuel cells accepting information from the biological environment and adjusting the electrical power production to the needs of the body. The system should allow collection of biochemical signals, processing of the obtained information, making decision and switch- ing / tuning the biofuel cell activity. This could be achieved by in- tegration of biocomputing/logic systems [8] with switchable/tunable biocatalytic electrodes [9] in a biofuel cell. Recently emerged research area of the enzyme logic systems has already resulted in the design of various logic gates (AND, OR, XOR, etc.) [10–13] and their networks composed of several concatenated logic gates [14,15] processing biochemical information. On the other side, switchable tunable bio- fuel cells controlled by external electrical [16] or magnetic [17] signals were reported recently. Concerted operation of the information processing units and the biofuel cell producing electrical energy requires interfacing of the biocomputing-enzyme logic systems with biocatalytic electrodes in the cell. Some examples of the interfacing between the enzyme logic gates with biocatalytic electrodes [18,19] and other bioelectronic devices [20] were reported recently. A biofuel cell composed of switchable electrodes controlled by a single AND/OR logic operation performed by an enzyme system was designed upon integration of the enzyme-information processing system and enzyme-power producing electrodes [21]. However, the most impor- tant feature of the enzyme logic systems is the ability to scale up their complexity [22] integrating single logic gates into complex logic networks similarly to the natural biochemical pathways. The very first example of an electrochemical interface functionally controlled by an enzyme logic network composed of many logic gates was reported recently [23]. The present paper is aimed one step forward to integrate an enzyme logic network with a biofuel cell illustrating the concept of “smart” biofuel cells logically responding to their biochemical environment. Bioelectrochemistry 76 (2009) 4–9 ⁎ Corresponding author. Tel.: +1 315 2684421; fax: +1 315 2686610. E-mail address: ekatz@clarkson.edu (E. Katz). 1567-5394/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.bioelechem.2009.03.008 Contents lists available at ScienceDirect Bioelectrochemistry journal homepage: www.elsevier.com/locate/bioelechem