Microfluidic paper-based analytical device for colorimetric detection of fluoride ion with smartphone readout.

Fluoride water contamination is a critical environmental challenge that poses a considerable threat to our society worldwide. This pollutant is widely dispersed, naturally occurring in groundwater through the solvent action of water on rocks and soil but also contributed by industrial activities such as aluminium and steel production, glass and semiconductor manufacturing, fertilizers, and electroplating. This dual origin highlights the urgent need for comprehensive strategies to address the global problem of fluoride contamination of water sources [1,2].

These problems affect regions worldwide and require effective defluoridation strategies to preserve water quality and public health. High fluoride in water causes dental and skeletal issues, bone damage, muscle weakness, fatigue, and severe health complications in organisms [3]. Because of these detrimental consequences, the World Health Organization (WHO) has established a maximum acceptable limit of 1.5 mg/L (78.9 uM) for drinking water [4]. Nevertheless, fluoride concentrations in diverse water sources worldwide surpass this prescribed standard so much attention has been paid to the development of analytical methods for fluoride ion detection.

There are well-established methods for determining fluoride in wastewater. Among the most commonly used methods are ion chromatography [5], mass spectrometry [6], and potentiometric methods [7]. Although these methods are highly sensitive and selective for fluoride determination, most of them require sample pretreatment, which makes in situ measurement difficult or impossible, which is primarily needed for fluoride determination in water. Additionally, their application typically requires specialized and expensive laboratory equipment, as well as qualified personnel to interpret the results.

Currently, there is a need to develop new analytical methodologies that allow for the rapid and simple detection and quantification of fluoride ions, without the need for sample pretreatment and using small volumes of samples and reagents. Thanks to the advancement of microfluidic paper-based analytical devices (uPAsD), different analytical strategies have been evaluated for fluoride ions determination. Among them, optical methods based mainly on colour and fluorescence changes stand out [[8], [9], [10], [11]].

All of these methods are based on the immobilization of dyes or fluorophores on paper devices developed for on-site fluoride detection without the need for sample pretreatment. These techniques emerge as an attractive alternative to conventional analysis methods. uPADs not only enable on-site measurements but also facilitate result interpretation through easily understandable colour changes for any user. However, a significant challenge in colorimetric determination with paper devices is colour interpretation, which can be subjective, especially at low concentrations of the compound of interest and can lead to false positives or negatives. Thus, digital imaging tools, especially smartphones, have emerged as powerful allies in enhancing both the sensitivity and usability of paper-based analytical devices. Their ability to detect slight colour changes, combined with image-based data processing, allows for more precise and quantitative interpretation of analytical results [12], [13]. To improve the sensitivity of these devices, the use of digital imaging devices, such as smartphones, scanners, or digital cameras, is often proposed to capture an image of the sensor area and interpret the colour through mathematical analysis [14]. This integration of imaging devices enhances the analytical performance of uPADs, enables quantitative analysis, allows for on-site measurements, and facilitates result interpretation through easily visible colour changes [[15], [16], [17]].

Another strategy to improve the sensitivity of these devices is related to recognition chemistry. Within this strategy, a key element in such a system is the use of a molecular sensor that can be prepared with ease and that can yield a significant colour change that can be observed with the naked eye, meaning a simpler colorimetric detection. Focused on such a sensor, we turned our attention to donor-acceptor (D-A) systems with simple yet robust synthetic procedures, and we found it in chemodosimeters derived from the dicyanomethylene-4H-pyran scaffold. To the best of our knowledge, only one of these systems has already been used in the detection of the fluoride anion as a turn-on sensor, although within the context of using fluorescence as the detection method [18] due to its high sensitivity. This chemosensor was investigated for its fluorescence properties in the NIR range, as it would exhibit reduced background emission and light scattering while also preventing tissue photodamage. However, for the present case of a colorimetric uPAD sensor, NIR fluorescence was not required, so a less conjugated structure could be employed; additionally, a more labile TBDMS ether instead of a TBDPS one could improve its sensitivity in a paper system. Therefore, we envisioned DCMSi as a convenient chemosensor for its application in uPAD systems, as it would maintain a similar optical behaviour (strong change in colour upon cleavage of the TBDMS moiety after treatment with fluoride) albeit not in the NIR range, due to the intramolecular charge transfer (ICT) mechanism exhibited by the resulting phenoxide ion.

We report a colorimetric fluoride paper-based sensor on which has been immobilized a styryl dihydropyranylidenmalononitrile with silyl ether group (DCMSi) that reacts selectively with salts containing the fluoride ions. The reaction towards the formation of the corresponding fluorosilane produces a strong colour change because of the donor-acceptor nature of the moieties involved in the organic probe. The results obtained demonstrate the reliability and accuracy of this new device for the determination of fluoride, making it a promising colorimetric sensor that stands out for its low cost, fast results, high selectivity, and very low detection limit.