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This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper's unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. This review discusses the fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability. [ABSTRACT FROM AUTHOR]

Inflammation caused by viral or bacterial infection is a major threat to human health globally. Blood C-reactive protein (CRP) has been proven to be a sensitive indicator for the occurrence and development of inflammation. Furthermore, a tiny change of blood CRP concentration may portend chronic diseases; therefore, high-sensitivity CRP (hs-CRP) detection in a quantitative, rapid, user-friendly, and low-cost manner is highly demanded. In this paper, we developed a europium-chelate polystyrene microsphere (EuPSM)-based lateral flow immunoassay (LFIA) integrating with a benchtop fluorescence analyzer for hs-CRP detection. The optimization of the EuPSM-based LFIA was implemented through adjusting the antibody density on EuPSM from 100% to 60% of the saturated density. Finally, the limit of detection of 0.76 pg/mL and detection range of 0.025–250 ng/mL were obtained. Moreover, the clinical application capability of the proposed platform was validated through detecting CRP in clinical serum samples, showing high consistency with the results obtained from the clinical standard method. Hence, the proposed EuPSM-based LFIA has been verified to be well suitable for hs-CRP detection, while also showing great applicability for sensitively and rapidly detecting other biomarkers. [ABSTRACT FROM AUTHOR]

Paper is a versatile, flexible, porous, and eco-friendly substrate that is utilized in the fabrication of low-cost devices and biosensors for rapid detection of analytes of interest. Paper-based sensors provide affordable platforms for simple, accurate, and rapid detection of diseases, in addition to monitoring food quality, environmental and sun exposure, and detection of pathogens. Paper-based devices provide an inexpensive technology for fabrication of simple and portable diagnostic systems that can be immensely useful in resource-limited settings, such as in developing countries or austere environments, where fully-equipped facilities and highly trained medical staff are absent. In this work, we present the different types of paper that are currently utilized in fabrication of paper-based sensors, and common fabrication techniques ranging from wax printing to origamiand kirigami-based approaches. In addition, we present different detection techniques that are employed in paper-based sensors such as colorimetric, electrochemical, and fluorescence detection, chemiluminescence, and electrochemiluminescence, as well as their applications including disease diagnostics, cell cultures, monitoring sun exposure, and analysis of environmental reagents including pollutants. Furthermore, main advantages and disadvantages of different types of paper and future trends for paper-based sensors are discussed. [ABSTRACT FROM AUTHOR]

This study describes the use of a smartphone for monitoring acid-base titrations on wax printed paper microzones. An array of twelve microzones of 5 mm diameter each was wax printed on filter paper. The analytical performance of the proposed devices was explored with acid-base titrations examples, where jaboticaba peel extract was used as a natural pH indicator. The color intensity was captured using a smartphone and analyzed through a free App named Photometrix®. Before titrations, color intensity versus pH was calibrated to be used as a reference in titrations as (i) strong acid versus strong base; (ii) strong base versus strong acid; and (iii) weak acid versus strong base. In all examples, images were obtained after the addition of each aliquot of titrant solutions. The obtained titration curves showed the same behavior as the conventional titration curves. After evaluating the feasibility of the proposed methodology, the concentration level of acetic acid was obtained in three vinegar samples. Although the obtained values ranged from 5% to 8% compared to the concentrations on the conventional method, the proposed methodology presented high analytical reliability. The calculated concentrations of acetic acid in three samples ranged from 3.87% to 3.93%, and the proposed methodology did not significantly differ from classic acid-base titration at a confidence level of 95%. The acid-base titration on paper-based devices is outstanding, since any titration can be completed within 5 min using 20 μL volumes. Besides, the use of a smartphone to capture images followed by analysis in a free app offers simplicity to all users. The proposed methodology arises as a new strand to be exploited in the diffusion of the analytical chemistry education field as well as an alternative for quantitative analysis with extremely simplified instrumentation. [ABSTRACT FROM AUTHOR]

This paper describes a paper-based colorimetric biosensor for measuring glucose concentration levels in human tear samples. Colorimetric biosensors were wax printed on paper platforms and modified with chitosan previously prepared in acetic acid. The proposed device was explored to measure the glucose levels in human tear samples using 3,30,5,50-tetramethylbenzydine (TMB) as the chromogenic reagent. The paper-based colorimetric biosensor exhibited a linear behavior for the glucose concentration range between 0.1 and 1.0 mM. The achieved analytical sensitivity and limit of detection (LOD) were 84 AU/mM and 50 M, respectively. Moreover, the device provided analytical reliability and no statistical difference when compared to the data recorded with a commercial glucometer. The proof-of-concept of our device was successfully demonstrated by measuring the glucose levels in six tear samples from nondiabetic subjects. In general, the results showed that the colorimetric biosensor has noticeable potential to be used as a powerful tool for tear glucose monitoring, since this fluid offers lower potential interferences, non-invasive sample collection and is pain-free. Furthermore, the proposed device could facilitate the treatment of diabetic patients who need constant control of glucose levels and cannot tolerate multiple finger sticks per day. [ABSTRACT FROM AUTHOR]

Fluid flow behaviour in paper is of increasing interest due to the advantages and expanding use of microfluidic paper-based analytical devices (known as μPADs). Applications are expanding from those which often have low sample fluid volumes, such as diagnostic testing, to those with an abundance of sample fluid, such as water quality testing. The rapid development of enhanced features in μPADs, along with a need for increased sensitivity and specificity in the embedded chemistry requires understanding the passively-driven fluid motion in paper to enable precise control and consistency of the devices. It is particularly important to understand the influence of parameters associated with larger fluid volumes and to quantify their impact. Here, we experimentally investigate the impacts of several properties during imbibition in paper, including geometry (larger width and length) and the surrounding conditions (humidity and temperature) using abundant fluid reservoirs. Fluid flow velocity in paper was found to vary with temperature and width, but not with length of the paper strip and humidity for the conditions we tested. We observed substantial post-wetting flow for paper strips in contact with a large fluid reservoir. [ABSTRACT FROM AUTHOR]

Lactate is an essential biomarker for determining the health of the muscles and oxidative stress levels in the human body. However, most of the currently available sweat lactate monitoring devices require external power, cannot measure lactate under low sweat rates (such as in humans at rest), and do not provide adequate information about the relationship between sweat and blood lactate levels. Here, we discuss the on-skin operation of our recently developed wearable sweat sampling patch. The patch combines osmosis (using hydrogel discs) and capillary action (using paper microfluidic channel) for long-term sweat withdrawal and management. When subjects are at rest, the hydrogel disc can withdraw fluid from the skin via osmosis and deliver it to the paper. The lactate amount in the fluid is determined using a colorimetric assay. During active sweating (e.g., exercise), the paper can harvest sweat even in the absence of the hydrogel patch. The captured fluid contains lactate, which we quantify using a colorimetric assay. The measurements show the that the total number of moles of lactate in sweat is correlated to sweat rate. Lactate concentrations in sweat and blood correlate well only during high-intensity exercise. Hence, sweat appears to be a suitable biofluid for lactate quantification. Overall, this wearable patch holds the potential of providing a comprehensive analysis of sweat lactate trends in the human body. [ABSTRACT FROM AUTHOR]

A digital microfluidic modular interface (chip-to-chip interface) which possesses an electrode with an orifice to vertically transport core–shell droplets is presented. The electrodes were geometrically designed to promote droplet deformation and suspension. The droplets were then applied with an electrical potential for insertion into and passage through the orifice. The concepts were tested with three types of droplets at the volume of 0.75~1.5 μL, which is usually difficult to transfer through an orifice. The integration of electrowetting on dielectric (EWOD) with paper-based microfluidics was demonstrated: the droplet could be transported within 10 s. More importantly, most of the core droplet (~97%) was extracted and passed through with only minimal shell droplets accompanying it. [ABSTRACT FROM AUTHOR]

The development of diagnostic tools for measuring a wide spectrum of target analytes, from biomarkers to other biochemical parameters in biological fluids, has experienced a significant growth in the last decades, with a good number of such tools entering the market. Recently, a clear focus has been put on miniaturized wearable devices, which offer powerful capabilities for real-time and continuous analysis of biofluids, mainly sweat, and can be used in athletics, consumer wellness, military, and healthcare applications. Sweat is an attractive biofluid in which different biomarkers could be noninvasively measured to provide rapid information about the physical state of an individual. Wearable devices reported so far often provide discrete (single) measurements of the target analytes, most of them in the form of a yes/no qualitative response. However, quantitative biomarker analysis over certain periods of time is highly demanded for many applications such as the practice of sports or the precise control of the patient status in hospital settings. For this, a feasible combination of fluidic elements and sensor architectures has been sought. In this regard, this paper shows a concise overview of analytical tools based on the use of capillary-driven fluidics taking place on paper or fabric devices integrated with solid-state sensors fabricated by thick film technologies. The main advantages and limitations of the current technologies are pointed out together with the progress towards the development of functional devices. Those approaches reported in the last decade are examined in detail. [ABSTRACT FROM AUTHOR]

Antibiotics are classes of antimicrobial substances that are administered widely in the field of veterinary science to promote animal health and feed efficiency. Cattle-administered antibiotics hold a risk of passing active residues to milk, during the milking process. This becomes a public health concern as these residues can cause severe allergic reactions to sensitive groups and considerable economic losses to the farmer. Hence, to ensure that the produced milk is safe to consume and adheres to permissible limits, an on-farm quick and reliable test is essential. This study illustrates the design and development of a microfluidic paper biosensor as a proof-of-concept detection system for gentamicin in milk. Localized surface plasmon resonance (LSPR) properties of gold nanoparticles have been explored to provide the user a visual feedback on the test, which was also corroborated by RGB analysis performed using Image J. The assay involves the use of a short stretch of single stranded DNA, called aptamer, which is very specific to the gentamicin present in the milk sample. The camera-based LOD for the fabricated paper device for milk samples spiked with gentamicin was calculated to be 300 nM, with a reaction time of 2 min. [ABSTRACT FROM AUTHOR]

In this paper, we report a simple and inexpensive paper-based microfluidic device for detecting nitrate in water. This device incorporates two recent developments in paper-based technology suitable for nitrate detection and has an optimized microfluidic design. The first technical advancement employed is an innovative fibrous composite material made up of cotton fibers and zinc microparticles that can be incorporated in paper-based devices and results in better nitrate reduction. The second is a detection zone with an immobilized reagent that allows the passage of a larger sample volume. Different acids were tested—citric and phosphoric acids gave better results than hydrochloric acid since this acid evaporates completely without leaving any residue behind on paper. Different microfluidic designs that utilize various fluid control technologies were investigated and a design with a folding detection zone was chosen and optimized to improve the uniformity of the signal produced. The optimized design allowed the device to achieve a limit of detection and quantification of 0.53 ppm and 1.18 ppm, respectively, for nitrate in water. This accounted for more than a 40% improvement on what has been previously realized for the detection of nitrate in water using paper-based technology. [ABSTRACT FROM AUTHOR]

The main problem for the expansion of the use of microfluidic paper-based analytical devices and, thus, their mass production is their inherent lack of fluid flow control due to its uncontrolled fabrication protocols. To address this issue, the first step is the generation of uniform and reliable microfluidic channels. The most common paper microfluidic fabrication method is wax printing, which consists of two parts, printing and heating, where heating is a critical step for the fabrication of reproducible device dimensions. In order to bring paper-based devices to success, it is essential to optimize the fabrication process in order to always get a reproducible device. Therefore, the optimization of the heating process and the analysis of the parameters that could affect the final dimensions of the device, such as its shape, the width of the wax barrier and the internal area of the device, were performed. Moreover, we present a method to predict reproducible devices with controlled working areas in a simple manner. [ABSTRACT FROM AUTHOR]

In healthcare, new diagnostic tools that help in the diagnosis, prognosis, and monitoring of diseases rapidly and accurately are in high demand. For in-situ measurement of disease or infection biomarkers, point-of-care devices provide a dramatic speed advantage over conventional techniques, thus aiding clinicians in decision-making. During the last decade, paper-based analytical devices, combining paper substrates and electrochemical detection components, have emerged as important point-of-need diagnostic tools. This review highlights significant works on this topic over the last five years, from 2015 to 2019. The most relevant articles published in 2018 and 2019 are examined in detail, focusing on device fabrication techniques and materials applied to the production of paper fluidic and electrochemical cell architectures as well as on the final device assembly. Two main approaches were identified, that are, on one hand, those ones where the fabrication of the electrochemical cell is done on the paper substrate, where the fluidic structures are also defined, and, on the other hand, the fabrication of those ones where the electrochemical cell and liquid-driving paper component are defined on different substrates and then heterogeneously assembled. The main limitations of the current technologies are outlined and an outlook on the current technology status and future prospects is given. [ABSTRACT FROM AUTHOR]

The main problem for the expansion of the use of microfluidic paper-based analytical devices and, thus, their mass production is their inherent lack of fluid flow control due to its uncontrolled fabrication protocols. To address this issue, the first step is the generation of uniform and reliable microfluidic channels. The most common paper microfluidic fabrication method is wax printing, which consists of two parts, printing and heating, where heating is a critical step for the fabrication of reproducible device dimensions. In order to bring paper-based devices to success, it is essential to optimize the fabrication process in order to always get a reproducible device. Therefore, the optimization of the heating process and the analysis of the parameters that could affect the final dimensions of the device, such as its shape, the width of the wax barrier and the internal area of the device, were performed. Moreover, we present a method to predict reproducible devices with controlled working areas in a simple manner.

In this paper, we report a simple and inexpensive paper-based microfluidic device for detecting nitrate in water. This device incorporates two recent developments in paper-based technology suitable for nitrate detection and has an optimized microfluidic design. The first technical advancement employed is an innovative fibrous composite material made up of cotton fibers and zinc microparticles that can be incorporated in paper-based devices and results in better nitrate reduction. The second is a detection zone with an immobilized reagent that allows the passage of a larger sample volume. Different acids were tested-citric and phosphoric acids gave better results than hydrochloric acid since this acid evaporates completely without leaving any residue behind on paper. Different microfluidic designs that utilize various fluid control technologies were investigated and a design with a folding detection zone was chosen and optimized to improve the uniformity of the signal produced. The optimized design allowed the device to achieve a limit of detection and quantification of 0.53 ppm and 1.18 ppm, respectively, for nitrate in water. This accounted for more than a 40% improvement on what has been previously realized for the detection of nitrate in water using paper-based technology.