Precision medicine in Alzheimer's disease: An origami paper-based electrochemical device for cholinesterase inhibitors

In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to deliver a costeffective and easy to use sensing tool for customized administration of drugs in Alzheimer's disease. Among several drugs, we designed the device for evaluating the efficacy of compounds (e.g. physostigmine, rivastigmine, donepezil) which are able to inhibit in a reversible way the cholinesterase enzyme. Because cholinesterase activity is peculiar to each patient, the administration of customized amount of the drug can improve the treatment efficacy and the quality of patient life, avoiding side effects due to the overdosage. In detail, we exploited VividTM Plasma Separation membrane to threat the whole blood sample, filter paper to load the reagents needed for the measurement, and office paper to print electrodes able to measure the butyrylcholinesterase activity, delivering a reagent free analytical tool. The calibration curve of butyrylcholinesterase obtained in blood sample provided linearity between 2 and 12 U/mL, with sensitivity of 0.050 +/- 0.004 mu A mL/U. The physostigmine, rivastigmine, and donepezil inhibition activities toward the butyrylcholinesterase enzyme were also measured in blood sample with linearity up to respectively 0.5 mu M, 25 mu M, 30 mu M, and detection limits of 0.009 mu M, 0.4 mu M, 0.3 mu M. These results demonstrate the capability of paper-based origami sensors as point of care devices to customize the drug administration in Alzheimer's disease.