Lab on a Chip PAPER Cite this: DOI: 10.1039/c3lc51098k Received 26th September 2013, Accepted 2nd December 2013 DOI: 10.1039/c3lc51098k www.rsc.org/loc A paper-based potentiometric cell for decentralized monitoring of Li levels in whole blood† Marta Novell, Tomàs Guinovart, Pascal Blondeau, F. Xavier Rius and Francisco J. Andrade* A novel approach to monitor Li levels in blood in decentralized (out of the lab) settings is presented. The approach uses a potentiometric cell fully made with filter paper as a support. Electrodes were built using carbon nanotubes ink to create a conductive path and a suitable polymeric membrane. Solid-state ion- selective electrodes for Li and a reference electrode were built and optimized. The results obtained on real samples of serum and whole blood are comparable with those obtained by conventional standard approaches. This platform shows an outstanding performance for the direct, fast and low-cost monitoring of Li levels in blood. Introduction Lithium is widely known as a mood stabilizer drug. Today, the administration of Li salts is a standard procedure to treat patients with some types of manic and bipolar disor- ders and recurrent depression. 1 Despite this wide utilization, the use of this drug is not free from risks and troubles. From one side, Li has a very narrow effective therapeutic range. For an effective treatment 2,3 the concentration of Li in blood must be adjusted (depending on the type of disor- der) to levels in the range of 0.5 to 1.5 mM. Levels below this range are not effective, while levels above it can lead to toxic effects. Chronic toxicity – with kidney, liver or brain function damage – is not a negligible problem, since long-term treat- ments (usually for years or decades) are fairly common. Acute toxicity is an even more worrisome problem, since concentrations in blood at around 5 mM may result in per- manent damage or even death. Reaching and sustaining the right therapeutic level while avoiding risks is not a simple task, since there are many fac- tors that affect lithium uptake and retention. It is well known that individual variability, as well as changes in salt intake, caffeine, drug interaction, etc. 4 may have a significant effect on the blood levels of Li. To find the right dosage, doctors must administer the drug and then check the actual Li levels in the blood, adjusting the dose until the right value is reached. 5 Blood samples must be taken at least 12 h after the last administration, and the whole analytical process may have a variable lag time (usually from a few days to weeks). Furthermore, Li levels in blood must then be monitored during the whole treatment. This whole approach is troublesome for both the healthcare professional and the patient. The need to have frequent blood tests is a nuisance for the patient, while the delay between the sample extraction and the evalua- tion of the results limits the possibility of early detection and correction of problems. Alternative approaches to alleviate this issue – such as monitoring the levels in urine or saliva – have been proposed, 6 but the results obtained are not yet reli- able. Thus, blood testing still remains as the gold standard. Evidently, approaches that could provide results in real time with minimal disruption for the patient will be highly desired. Although several methods for the measurement of lithium in blood, such as colorimetry 7 or photometry, 8–10 have been reported, routine analysis is usually performed by flame emis- sion photometry, atomic absorption spectroscopy or ion selec- tive electrodes. 2,11 Evidently, all these determinations must be performed in a laboratory, with suitable expertise and instru- mentation. The need to have quicker and simpler ways to determine the levels of Li in blood has motivated the develop- ment of several decentralized approaches, such as those used in point-of-care testing. 12 Glazer et al. 10 have reported an instant test that allows the quantification of lithium in plasma by means of photometry. The test is composed of a blood–cell separator membrane linked to a micro-cuvette prefilled with a colorimetric reagent. Van den Berg et al. 13–16 have developed a point-of-care hand-held analyser that uses prefilled disposable chips with integrated microfluidics, where the blood components are separated by capillary electrophoresis and lithium is detected by conductimetry. Lab Chip This journal is © The Royal Society of Chemistry 2014 Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, Carrer Marcel.lí Domingo s/n, 43007 Tarragona, Spain. E-mail: franciscojavier.andrade@urv.cat † Electronic supplementary information (ESI) available. See DOI: 10.1039/c3lc51098k Published on 03 December 2013. Downloaded by Universitat Rovira I Virgili on 10/02/2014 15:20:07. View Article Online View Journal