Chip level agitation effects on the electrochemical sensing of alkaline-phosphatase expressed from integrated liver tissue

Integrated “tissue on a chip” system with chip-level agitation apparatus has been tested for alkaline phosphatase (ALP) sensing from integrated live tissues on chip. The system was tested and the results are compared to the solutions of a simple 1D models. The models assume electrochemical monitoring of ALP activity with 1-naphtyl phosphate (1-NP) substrate in freshly recovered small tissue samples placed in a micro-electrochemical cell with and without agitation in the 0–12 Hz frequency range. The results indicated on more than an order of magnitude increase in the alpha-naphthol (α-NAP) product oxidation current for samples with agitation compared to non-agitated measurements. The models assume that ALP expressed in the cells (mainly localized in the microvilli of the hepatocytes canalicular membrane) and that part of it is secreted outside of the tissue. The product percolates through the extracellular matrix or leaks out via truncated blood vessels. Once out of the tissue, the product is rapidly distributed throughout the electrolyte and can be oxidized at the working electrode. The measured current and effective charge at long time periods increased as t1/2 and t3/2 respectively. This pointed toward diffusion-limited condition; however, convection should not be excluded. The agitation probably affects the rate of excretion of the product from the tissue and the transfer from the tissue to the electrolyte. Finally, we discuss the applicability of such method for point-of-care application. We present a short discussion and an approach to make such “tissue on a chip” useful for an automated point of care application. To improve accuracy, stability and reproducibility we discuss our approach for a post measurement digital signal processing of the output variable (e.g. current, charge, etc.), providing the best signal to noise ratio.