# Organic Electrochemical Transistor Microplate for Real-Time Cell Culture Monitoring
## 1 Introduction  
The current trend in toxicology and pharmacology focuses on the substitution of experimental animals with in-vitro cell-based systems. This requires the introduction of approaches for the real-time determination of cell physiology. Electrochemical sensors can serve this purpose. Furthermore, the use of organic semiconductors allows for the production of disposable sensors at a low cost. Poly(3,4-ethylenedioxythio-pheno) mixed with poly(styrene sulfonic acid)--(PEDOT:PSS) has become the most convenient material among organic semiconductors for bioelectronic applications because of its high conductivity and biocompatibility. The theoretical model of an Organic Electrochemical Transistor (OECT) based on PEDOT:PSS, which was published in 2007 [1], has enabled the optimization and further development in bioelectronic applications. The model describes both the steady state andtransient response of the ionic and hole channel current on gate voltage. An amended model taking into account nonlinearities in charge carrier mobility and optical absorption variation was presented in 2015 [2]. The functional improvement consists of geometry optimization in order to maximize the OECT transconductance [3], working point setting to zero gate voltage [4], miniaturizing for one cell monitoring down to a channel length of 6 \(\upmu\)m, and a fast response down to a 100 \(\upmu\)s time constant [5].  
The OECT architecture can be planar, when the PEDOT:PSS channel and gate are deposited by spin coating, inkjet printing [6], and screen printing methods, as well as using the microlithographic technique. The gate electrode can either be situated in the electrolyte bulk above the channel using gold or Ag/AgCl wire as a biocompatible material or be deposited as a part of a planar electrode system on a substrate.  
Several reviews have been dedicated to both the investigation of general properties [7] and biological applications [8; 9; 10]. According to a recent review [11], biological applications can target several specific goals: ion sensors, enzymatic sensors, and immunosensors-nucleotide sensors, coupled with entire cells for electrophysiology, the integration of OECTs with nonelectrogenic cells, OECT for stimulations, and the recording of electrogenic cells. These have already been tested in human biology and experimental medicine either for diagnostics or treatment [12]. Others have combined optical and electrical sensing for the investigation of epithelial cells [13]. The OECT channel coverage by cells was evaluated by the time response of the channel current on the gate rectangular pulse. [PERSON] et al. [14] used OECT in a resorbable bioscaffold from poly(L-lactide-_co_-glycolide) for cardiographic recording.  
[PERSON] et al. (2013) [15] investigated the influence of antiarrhythmic drugs on cardiomyocytes by the simultaneous monitoring of the impedance signal of a cell set in a biosensor plate well containing a gold electrode system. Later, [PERSON] et al. (2015) [16] used a similar well plate equipped with OECTs for signal amplification. [PERSON] et al. (2015) [17] successfully used OECTs in recording the cardiac rhythm, eye movement, and brain activity of a human volunteer. [PERSON] et al. (2015) [18] reported the fabrication of a 3D biocompatible macroporous PEDOT:PSS scaffold supporting the fibroblast culture and the ability to electrically monitor various cell functions. They observed a positive potential influence on cell adherence enhancement, resulting in a higher relative number of adhered cells on an oxidized (+1 V) surface. [PERSON] et al. (2016) [19] developed an electrophysiological biosensor for investigating the electrogenic activity of cardiac cells by means of a multi-electrode array.  
The goal of this study is to investigate the possibility of OECTs based on the application of PEDOT:PSS and fabrication of a planar all-screen-printed 12 \(\times\) 8 microplate array of transistors.