Search

Timely and rapid detection of biomarkers is extremely important for the diagnosis and treatment of diseases. However, going to the hospital to test biomarkers is the most common way. People need to spend a lot of money and time on various tests for potential disease detection. To make the detection more convenient and affordable, we propose a paper-based aptasensor platform in this work. This device is based on a cellulose paper, on which a three-electrode system and microfluidic channels are fabricated. Meanwhile, novel nanomaterials consisting of amino redox graphene/thionine/streptavidin-modified gold nanoparticles/chitosan are synthesized and modified on the working electrode of the device. Through the biotin-streptavidin system, the aptamer whose 5'end is modified with biotin can be firmly immobilized on the electrode. The detection principle is that the current generated by the nanomaterials decreases proportionally to the concentration of targets owing to the combination of the biomarker and its aptamer. 17β-Estradiol (17β-E2), as one of the widely used diagnostic biomarkers of various clinical conditions, is adopted for verifying the performance of the platform. The experimental results demonstrated that this device enables the determination of 17β-E2 in a wide linear range of concentrations of 10 pg mL-1 to 100 ng mL-1 and the limit of detection is 10 pg mL-1 (S/N = 3). Moreover, it enables the detection of targets in clinical serum samples, demonstrating its potential to be a disposable and convenient integrated platform for detecting various biomarkers.

In this work, we fabricated a novel origami paper-based analytical device (oPAD) assisted by the nanostructuring effect of in situ Pd decoration of Cu/Co-doped CeO2 (CuCo-CeO2-Pd) nanospheres, functionalized with their strongly enhanced electrocatalytic properties to realize an electrochemical and visual signal readout system in oPAD, for highly sensitive detection of amyloid-β (Aβ). The CuCo-CeO2-Pd nanospheres were introduced as an enhanced "signal transducer layer" on account of the electron transfer acceleration caused by catalyzing glucose to produce H2O2 for differential pulse voltammetry signal readout and further 3,3'5,5'-tetramethylbenzidine (TMB) oxidation for colorimetric analysis. Meanwhile, for achieving superior performance of the proposed oPAD, in situ growth of urchin-like gold nanoparticles (Au NPs) onto cellulose fibers was adopted to improve "the recognition layer" in favor of immobilizing antibodies for targeting Aβ through specific antigen-antibody interactions. Combined with the delicate design of oPAD, exhibiting actuation of the conversion procedure between hydrophobicity and hydrophilicity on paper tabs in the assay process, the oPAD successfully enabled sensitive diagnosis of Aβ in a linear range from 1.0 pM to 100 nM with a limit of detection of 0.05 pM (S/N = 3) for electrochemical detection, providing a reliable strategy for quantifying the Aβ protein in clinical applications. Ministry of Education (MOE) This work was financially supported by the Science and Technology Projects of University of Jinan (XKY2002), the Natural Science Foundation of Shandong Province (ZR2020MB057), the Singapore Ministry of Education (MOE AcRF Tier 1 RG176/16), the Taishan Scholars Program, the Case-by-Case Project for Top Outstanding Talents of Jinan, and the project of "20 Items of University" of Jinan (2018GXRC001).

Novel ways to track and verify items of a high value or security is an ever-present need. Taggants made from deoxyribonucleic acid (DNA) have several advantageous properties, such as high information density and robust synthesis; however, existing methods require laboratory techniques to verify, limiting applications. Here, we leverage DNA nanotechnology to create DNA taggants that can be validated in the field in seconds to minutes with a simple equipment. The system is driven by toehold-mediated strand-displacement reactions where matching oligonucleotide sequences drive the generation of a fluorescent signal through the potential energy of base pairing. By pooling different "input" oligonucleotide sequences in a taggant and spatially separating "reporter" oligonucleotide sequences on a paper ticket, unique, sequence-driven patterns emerge for different taggant formulations. Algorithmically generated oligonucleotide sequences show no crosstalk and ink-embedded taggants maintain activity for at least 99 days at 60 °C (equivalent to nearly 2 years at room temperature). The resulting fluorescent signals can be analyzed by the eye or a smartphone when paired with a UV flashlight and filtered glasses.

On-site detection of multiple small-molecule analytes in complex sample matrixes would be highly valuable for diverse biosensing applications. Paper electrochemical devices (PEDs) offer an especially appealing sensing platform for such applications due to their low cost, portability, and ease of use. Using oligonucleotide-based aptamers as biorecognition elements, we here for the first time have developed a simple, inexpensive procedure for the fabrication of aptamer-modified multiplex PEDs (mPEDs), which can robustly and specifically detect multiple small molecules in complex samples. These devices are prepared via an ambient vacuum filtration technique using carbon and metal nanomaterials that yields precisely patterned sensing architecture featuring a silver pseudo-reference electrode, a gold counter electrode, and three gold working electrodes. The devices are user-friendly, and the fabrication procedure is highly reproducible. Each working electrode can be readily modified with different aptamers for sensitive and accurate detection of multiple small-molecule analytes in a single sample within seconds. We further demonstrate that the addition of a PDMS chamber allows us to achieve detection in microliter volumes of biological samples. We believe this approach should be highly generalizable, and given the rapid development of small-molecule aptamers, we envision that facile on-site multi-analyte detection of diverse targets in a drop of sample should be readily achievable in the near future.

The plasmonic properties of gold nanoparticles (AuNPs) are a promising tool to develop sensing alternatives to traditional, enzyme-catalyzed reactions. The need for sensing alternatives, especially in underdeveloped areas of the world, has given rise to the application of nonenzymatic sensing approaches paired with cellulosic substrates to biochemical analysis. Herein, we present three individual, low-step, wet-chemistry, colorimetric assays for three target biomarkers, namely, glucose, uric acid, and free cholesterol, relevant in diabetes control and their translation into paper-based assays and microfluidic platforms for multiplexed analysis. For glucose determination, an in situ AuNPs synthesis approach was applied into the developed μPAD, giving semiquantitative measures in the physiologically relevant range. For uric acid and cholesterol determination, modified AuNPs were used to functionalize paper with a gold-on-paper approach with the optical properties changing based on different aggregation degrees and hydrophobic properties of particles dependent on analyte concentration. These paper-based assays show sensitivity ranges and limits of detection compatible for target analyte level determination and detection limits comparable to those of similar enzymatic, colorimetric systems, relying only on plasmonic transduction without the need for enzymatic activity or other chromogenic substrates. The resulting paper-based assays were integrated into a single 3D, multiplex paper-based device using paper microfluidics, showing the capability for performing different colorimetric assays with distinct requirements in terms of sample flow and sample uptake in test zones using a combination of both horizontal and vertical flows inside the same device. The presented device allows for multiparametric, colorimetric measures of different metabolite levels from a single complex sample matrix drop using digital color analysis, showing the potential for development of low-cost, low-complexity tools for diagnostics toward the point-of-care.

Starch and derivatives thereof have proven their usefulness in paper coating processes. Among these derivatives, cationic starch has been widely used in the paper industry as a flocculation, dispersion and ink fixing agent. In another context, nanoscale cellulosic materials have been shown to improve the strength, retention of fillers, the barrier properties of packaging paper products, and printing qualities. This review summarizes the recent studies on the general components used in paper coating, describes the conventional and alternative synthetic processes of cationic starches and nanocellulose, and deals with their current and potential applications in papermaking, focusing primarily on surface treatments. Moreover, environmental applications have been considered to expand the understanding and usefulness of these materials. Further research on modified polysaccharides is encouraged to replace, in a feasible way, petro-based components of coating formulations, and to provide paper surfaces with new properties.

Tuberculosis (TB), one of the deadliest infectious diseases, is caused by Mycobacterium tuberculosis (MTB) and remains a public health problem nowadays. Conventional MTB DNA detection methods require sophisticated infrastructure and well-trained personnel, which leads to increasing complexity and high cost for diagnostics and limits their wide accessibility in low-resource settings. To address these issues, we have developed a low-cost photothermal biosensing method for the quantitative genetic detection of pathogens such as MTB DNA on a paper hybrid device using a thermometer. First, DNA capture probes were simply immobilized on paper through a one-step surface modification process. After DNA sandwich hybridization, oligonucleotide-functionalized gold nanoparticles (AuNPs) were introduced on paper and then catalyzed the oxidation reaction of 3,3',5,5'-tetramethylbenzidine (TMB). The produced oxidized TMB, acting as a strong photothermal agent, was used for the photothermal biosensing of MTB DNA under 808 nm laser irradiation. Under optimal conditions, the on-chip quantitative detection of the target DNA was readily achieved using an inexpensive thermometer as a signal recorder. This method does not require any expensive analytical instrumentation but can achieve higher sensitivity and there are no color interference issues, compared to conventional colorimetric methods. The method was further validated by detecting genomic DNA with high specificity. To the best of our knowledge, this is the first photothermal biosensing strategy for quantitative nucleic acid analysis on microfluidics using a thermometer, which brings fresh inspirations on the development of simple, low-cost, and miniaturized photothermal diagnostic platforms for quantitative detection of a variety of diseases at the point of care.

Paper is emerging as a versatile platform for automated fluid handling with a broad range of applications in medical diagnostics and analytical chemistry. However, selectively controlling analyte transport in paper to achieve concentration or selection has been a challenge for functional analysis. Here, by combining paper-based microfluidics with acoustics, we present a rapid and powerful method to size dependently control movement of microparticles and cells in paper using surface acoustic waves (SAW). We demonstrate the unique capability of the paper-based SAW approach to trap and concentrate microparticles in paper and release them when required, achieving collection efficiency of over 98%. Given the correlation between collection efficiency, size, and applied power, the paper-based SAW approach is applied to isolate a mixture of microparticles (1.1, 3.2, and 5 μm in diameter) into different regions and also to trap and concentrate human prostate cancer PC3 cells at a predetermined site. This paper-based SAW approach provides opportunities to develop powerful and low-cost selection and analysis tools, capable of processing complex multicomponent samples, with potential applications in medical diagnostics.

Paper-based microfluidic device was designed with wax-printing to combine potentiometric, fluorimetric and colorimetric detection zones. This newly developed trimodal paper chip has been used for on-site determination of ketamine hydrochloride (KET) as a date rape drug in beverages. The device employed polyaniline nano-dispersion as conducting polymer in ion sensing paper electrodes designed to fit USB plug connector. Carbon dots-gold nanoparticles and cobalt thiocyanate were used in fluorescence and color detection zones, respectively. Cellular phone's camera facilitated the on-site fluorimetric and color detection. The implemented trimodal detection system exhibited specificity for KET detection in the presence of several other beverage interferences i.e., biogenic amines. This innovative sensor brings together analytical figures of merit for effective KET detection in single aliquot of spiked beverages. The proposed paper-based chip also fulfils WHO criteria for point-of-care devices posing the proposed trimodal paper device as an active part for rapid, on-site drug diagnostics and to be applied further for other similar drugs.

Cotton is cheap, easily available and widely used as surgical material. Therefore, cotton would be good raw material to design a scaffold for tissue engineering applications. In this work, the gelatin-coated microfibrous paper scaffold was fabricated successfully by a papermaking process. Microfibers-based scaffold could overcome the limitations of nanofibrous material-based scaffold for tissue engineering application. The physicochemical and mechanical properties of the scaffolds were characterized. The results revealed that the gelatin contributed to the enhanced cell attachment and proliferation over the scaffolds, whereas cellulose as a strong backbone in the scaffold to support it for keeping its appearance. Their tensile strength and water absorption capacity were improved, but pore size and porosity were decreased after incorporation of gelatin. Hence, results suggested that fabricated scaffolds have huge prospective as a bioactive, well-designed and economical scaffold stand for tissue engineering application.

Because of numerous inherent and unrivaled features of nanofibers made of chitin, the second most plentiful natural-based polymer (after cellulose), including affordability, abundant nature, biodegradability, biocompatibility, commercial availability, flexibility, transparency, and extraordinary mechanical and physicochemical properties, chitin nanofibers (ChNFs) are being applied as one of the most appealing bionanomaterials in a myriad of fields. Herein, we exploited the beneficial properties offered by the ChNF paper to fabricate transparent, efficient, biocompatible, flexible, and miniaturized optical sensing bioplatforms via embedding/immobilizing various plasmonic nanoparticles (silver and gold nanoparticles), photoluminescent nanoparticles (CdTe quantum dots, carbon dots, and NaYF4:Yb3+@Er3+&SiO2 upconversion nanoparticles) along with colorimetric reagents (curcumin, dithizone, etc.) in the 3D nanonetwork scaffold of the ChNF paper. Several configurations, including 2D multi-wall and 2D cuvette patterns with hydrophobic barriers/walls and hydrophilic test zones/channels, were easily printed using laser printing technology or punched as spot patterns on the dried ChNF paper-based nanocomposites to fabricate the (bio)sensing platforms. A variety of (bio)chemicals as model analytes were used to confirm the efficiency and applicability of the fabricated ChNF paper-based sensing bioplatforms. The developed (bio)sensors were also coupled with smartphone technology to take the advantages of smartphone-based monitoring/sensing devices along with the Internet of Nano Things (IoNT)/the Internet of Medical Things (IoMT) concepts for easy-to-use sensing applications. Building upon the unrivaled and inherent features of ChNF as a very promising bionanomaterial, we foresee that the ChNF paper-based sensing bioplatforms will emerge new opportunities for the development of innovative strategies to fabricate cost-effective, simple, smart, transparent, biodegradable, miniaturized, flexible, portable, and easy-to-use (bio)sensing/monitoring devices., Financial support from the Chemistry & Chemical Engineering Research Centre of Iran (Tehran, Iran), Iran’s National Elites Foundation (INEF), Nano Novin Polymer Co. (Iran), and the Nano Match program of Iran Nanotechnology Initiative Council (INIC) are gratefully acknowledged. The ICN2 is funded by the CERCA Programme/Generalitat de Catalunya. The ICN2 is supported by the Severo Ochoa program of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO; grant nos. SEV-2017-0706 and MAT2017-87202-P). The financial support of “the Czech Science Foundation (No. 19-00676S)” is also greatly appreciated.

Real-time monitoring of neonicotinoid pesticide residues is of great significance for food security and sustainable development of the ecological environment. Herein, a paper-based surface-enhanced Raman scattering (SERS) amplified approach was proposed by virtue of multilayered plasmonic coupling amplification. The unique plasmonic SERS multilayer was constructed using three-dimensional (3D) silver dendrite (SD)/electropolymerized molecular identifier (EMI)/silver nanoparticle (AgNP) sandwich hybrids with multiple hotspots and a strong electromagnetic field in nanogaps. Dendritelike 3D silver materials with remarkably high accessible surface areas and the lightning rod effect constituted the first-order enhancement of paper-based sensors. Molecular identifiers coated upon an SD layer as the interlayer were used for target capture and enrichment. Subsequently, AgNPs featuring rough surface and local plasma resonance decorated as the top layer formed the secondary enhancement of the amplification strategy. As the most brilliant part, dendritelike 3D silver coupled with AgNPs has established double Ag layers to accomplish a multistage enhancement of SERS signals based on the superposition of their electromagnetic fields. Owning to the distinctive design of the multiple coupling amplification strategy, the fabricated SERS paper chips demonstrated impressive specificity and ultrahigh sensitivity in the detection of imidacloprid (IMI), with a detection limit as low as 0.02811 ng mL-1. More importantly, the multiple SERS enhancement paper chip holds great potential for automated screening of a variety of contaminants.

In the present article we report a new hybrid microfluidic device (hyFlow) comprising a disposable paper electrode and a three-dimensional (3D) printed plastic chip for the electrochemical detection of a magnetic bead-silver nanoparticle (MB-AgNP) bioconjugate. This hybrid device evolved due to the difficulty of incorporating micron-scale MBs into paper-only fluidic devices. Specifically, paper fluidic devices can entrap MB-containing conjugates within their cellulose or nitrocellulose fiber matrix. The hyFlow system was designed to minimize such issues and transport MB conjugates more efficiently to the electrochemical detection zone of the device. The hyFlow system retains the benefit of fluid transport by pressure-driven flow, however, no pump is required for its operation. The hyFlow device is capable of detecting either pre-formed MB-AgNP conjugates or conjugates formed in-situ formation. The detection limit of AgNPs using this device is 12 pM, which represents just 22 AgNPs per MB.

Rising concern about the use of non-permitted colourants, in common food items such as dals and green vegetables sold in Indian markets, have led to a demand for low-cost point-of-use chemical analysis tools. Conventional food-analysis techniques involving tedious sample preparation protocols are not suited for in-field applications. Surface Enhanced Raman Spectroscopy (SERS) is an analytical technique that is well-suited for point-of-use chemical analysis with molecular level detection capability, which can also serve as a quality assurance tool for businesses. Effective and rapid signal collection from a large-area sample within a field-setting using disposable, low-cost SERS substrates is a key challenge in implementing such a solution. Herein, we demonstrate the use of inkjet-printed thin films comprising of robust nanostructured-silver as flexible, paper-based SERS (P-SERS) swabs for the direct detection of Metanil Yellow (MY) from toor dal (yellow split pigeon peas) samples and Malachite Green (MG) from green peas and green chillies. The macroscopic uniformity of these thin-films in combination with a portable Raman spectrometer equipped with orbital raster scanning (ORS™) technology for signal collection results in an unprecedented precision (RSD ∼ 1.6%) upon characterizing samples saturated with Rhodamine-6G (R6G), a standard Raman probe. As several food-cleansing products have appeared in the marketplace, the adulterant removal efficacy of some commercially available ‘washes’ as well as products such as ‘ozoniser’, which was determined by SERS characterization of swabs before and after use, is also reported.

Owing to its critical role in the development of female reproductive tissues and as a clinical biomarker, there is an urgent need to develop a rapid and cost-effective method to sensitively detect 17β-estradiol (E2). In this work, a folding aptasensor platform with microfluidic channels for the label-free electrochemical detection of E2 is described. The platform, designed with a delicate folding structure, integrating filter holes, microfluidic channels, reaction chambers, and a three-electrode system, is extremely easy to use. To increase the detection sensitivity and immobilize the aptamer, we synthesized a novel nanoassembly consisting of amine-functionalized single-walled carbon nanotube/new methylene blue/gold nanoparticles (AuNPs) and modified the working electrode with this nanoassembly. The calibration curve obtained from the experimental results exhibited a linear range between 10 pg mL-1 and 500 ng mL-1 (R2 = 0.993), and a detection limit of 5 pg mL-1 was achieved (S/N = 3). Furthermore, experiments to detect E2 in clinical serum were conducted, and the results were highly similar to those obtained using a large electrochemical luminescence apparatus. By integrating multiple functional components, adopting novel nanoassemblies, and using a folding structure, this paper-based platform not only has great potential as a simple and convenient integrated device for point-of-care testing of E2, but also as a portable, low-cost, and highly sensitive aptasensor platform capable of detecting many diagnostic biomarkers with the appropriate aptamers.

Microfluidic paper-based sensors as a new type of microsample detection technology are widely used in medical diagnosis, environmental monitoring, and food safety testing. Inkjet printing has the advantages of simplicity, speed, flexibility, high resolution, low cost, and efficient mass production and has become one of the most cutting-edge technologies in the manufacture of paper-based sensors. In this work, a fully inkjet printing preparation method was proposed for paper-based sensors, which can achieve high-precision, multichannel, and visual fluorescence detection. Three kinds of fluorescent carbon dots (CDs; r-CDs, b-CDs, and y-CDs) were fabricated into inkjet ink by adding a suitable ratio of solvent, PEG, and surfactant FS3100 to control its viscosity, surface tension, and other influencing factors, obtaining the best-visualized fluorescence response on paper. To optimize the full inkjet printing process of the paper-based sensor, we studied the influence of factors such as the hydrophobic material AKD formula, postprocessing conditions, and the structure of the hydrophilic and hydrophobic channels on the paper-based detection accuracy, and it was found that proper AKD concentration, curing time, and temperature can make AKD fully react with paper-based surface groups and produce more hydrophobic groups on the surface and inside of the filter paper, which can form paper-based microfluidic sensors with clear boundaries and fast transmission speed at low cost and high efficiency. The fabricated sensor is used for the fluorometric determination of vitamin C (AA), NO2-, and sunset yellow (SY) at the same time, and the limits of visual detection by eyes are 6 mmol/L (NO2-), 60 μmol/L (SY), and 40 mmol/L (AA). The mechanism of inkjet printing is investigated in detail, which is simple, reliable, and easy to realize mass production and can realize highly sensitive, on-site, and visual detection for food additives.

The article is devoted to the consideration of the possibility of using fullerene-containing water as part of humic growth-stimulating preparations for agriculture with the addition of yeast production waste. More recently, the problems of the economy and the environment were perceived as opposite. Currently, there is a need for a mutually dependent and mutually beneficial combination of economic and environmental interests, which was the basis for this study. The analysis of the wastewater of the yeast-producing enterprise shows the presence of a large number of chemical and organic substances that pose a certain danger to the environment, but are useful after processing waste for use in agriculture. The largest number of substances is found in waste, after the stage of production of pure culture. The experiment shows that the use of structured water in combination with biologically active waste from the production of bread yeast obtained on the basis of the Saccharomyces cerevisiae strain increases the yield of grain crops. Based on the established fact of a wide and universal spectrum of biological activity of the water-carbon structure of hydrated fullerenes, according to patent and scientific and technical literature, they have not been widely tested as plant growth regulators. We will investigate the interaction of substances with water structured with fullerenes, the effect of surfactants on the formation and stability of emulsified humates with film-forming agents, the adhesive properties of the components, the effect of concentrated yeast fermentation liquid separated after the stage of growing a pure culture of baking yeast, the effect of both a fullerene-like structure – shungite of natural origin and hydrated fullerenes – highly stable finely dispersed aqueous solutions of native fullerenes (have the properties of lyophobic molecular colloidal systems) on grain yield, protection of vegetative plants. The result of the work will be the substantiation of the principles of the methodology for the application of nanostructured substances for use in biotechnologies of multifunctional highly effective drugs for agriculture with biologically active additives., Стаття присвячена розгляду питання про можливість застосування фуллереновмістної води в складі гуміновмісних ростостимулюючих препаратів для сільського господарства з додаванням відходів дріжджового виробництва. Зовсім недавно проблеми економіки та екології сприймали як протилежні. В даний час виникла необхідність взаємообумовленого і взаємовигідного поєднання економічних і екологічних інтересів, що стало основою для проведення даного дослідження. Аналіз стічних вод підприємства, що виробляє дріжджі показує наявність великої кількості хімічних і органічних речовин, які становлять певну небезпеку для навколишнього середовища, але представляє корисність після переробки відходів для використання в сільському господарстві. Найбільша кількість речовин знаходиться у відходах, після етапу виробництва чистої культури. В експерименті показано, що застосування структурованої води в поєднанні з біологічно активними відходами виробництва хлібних дріжджів, отриманими на основі штаму Saccharomyces cerevisiae збільшують врожайність зернових культур. Виходячи зі встановленого факту широкого і універсального спектра біологічної активності водно-вуглецевої структури гідратованих фулеренів, за даними патентної та науково-технічної літератури, вони широко не випробовувалися як регулятори росту рослин. Нами буде досліджено взаємодію речовин зі структурованою фулеренами водою, досліджено вплив поверхнево-активних речовин на утворення та стабільність емульгованих гуматів з плівко утворювачами, адгезивні властивості компонентів, вплив концентрованої бродильної рідини дріжджів відсепарованої після стадії вирощування чистої культури хлібопекарських дріжджів, випробувано вплив як фулереноподібної структури-шунгіту природного походження так і гідратованих фулеренів - високостабільних дрібнодисперсних водних розчинів нативних фулеренів (мають властивості ліофобних молекулярно-колоїдних систем) на врожайність зернових, захист вегетуючих рослин. Результатом роботи буде обґрунтування принципів методології застосування наноструктурних речовин для використання в біотехнологіях багатофункціональних високоефективних препаратів для сільського господарства з біологічно активними добавками.

With the outbreak and pandemic of COVID-19, point-of-care testing (POCT) systems have been attracted much attention due to their significant advantages of small batches of samples, user-friendliness, easy-to-use and simple detection. Among them, flexible biosensors show practical significance as their outstanding properties in terms of flexibility, portability, and high efficiency, which provide great convenience for users. To construct highly functional flexible biosensors, abundant kinds of polymers substrates have been modified with sufficient properties to address certain needs. Paper-based biosensors gain considerable attention as well, owing to their foldability, lightweight and adaptability. The other important flexible biosensor employs textiles as substrate materials, which has a promising prospect in the area of intelligent wearable devices. In this feature article, we performed a comprehensive review about the applications of flexible biosensors based on the classification of substrate materials (polymers, paper and textiles), and illustrated the strategies to design effective and artificial sensing platforms, including colorimetry, fluorescence, and electrochemistry. It is demonstrated that flexible biosensors play a prominent role in medical diagnosis, prognosis, and healthcare.

We thank the UK Engineering and Physical Sciences Research Council for funding (Grant Nos. EP/P030017/1 and EP/R004854/1). Significance: Optical trapping is a technique capable of applying minute forces that has been applied to studies spanning single molecules up to microorganisms. AIM: The goal of this perspective is to highlight some of the main advances in the last decade in this field that are pertinent for a biomedical audience. Approach: First, the direct determination of forces in optical tweezers and the combination of optical and acoustic traps, which allows studies across different length scales, are discussed. Then, a review of the progress made in the direct trapping of both single-molecules, and even single-viruses, and single cells with optical forces is outlined. Lastly, future directions for this methodology in biophotonics are discussed. Results: In the 21st century, optical manipulation has expanded its unique capabilities, enabling not only a more detailed study of single molecules and single cells but also of more complex living systems, giving us further insights into important biological activities. Conclusions: Optical forces have played a large role in the biomedical landscape leading to exceptional new biological breakthroughs. The continuous advances in the world of optical trapping will certainly lead to further exploitation, including exciting in-vivo experiments. Publisher PDF

We present a facile paper-based microfluidic device fabrication technique leveraging off-the-shelf carbon paper for the deposition of hydrophobic barriers using a novel "stencil scratching" method. This exceedingly frugal approach (0.05$) requires practically no technical training to employ. Hydrophobic barriers fabricated using this approach offer a width of 3 mm and a hydrophilic channel width of 849 μm, with an ability to confine major aqueous solvents without leakage. The utility of the device is demonstrated by porting a cell viability assay showing a limit-of-detection (LOD) of 0.6 × 108 CFU mL-1 and bilirubin assay with human serum showing a detection range of 1.76-6.9 mg dL-1 and a limit-of-detection (LOD) of 1.76 mg dL-1. The intuitiveness and economic viability of the fabrication method afford it great potential in the field of point-of-care diagnostics geared towards providing testing infrastructure in resource-scarce regions globally.

Rapid and sensitive detection of enteropathogenic Escherichia coli (EPEC) in fluids with complex background is an important task for safety quality control in the field of medicine, environment, and food. In this study, a gold foil paper–based aptasensor was developed for the detection of enteropathogenic EPEC O26:K60 with surface-enhanced Raman spectroscopy (SERS) and magnetic separation technology mediated by Fe3O4@Au composite. The gold foil paper was firstly modified with thiolated capture probe and SERS tag. The thiolated aptamer probe for EPEC was immobilized onto a Fe3O4@Au composite. In the presence of EPEC, highly specific recognition between the aptamer probe and EPEC made the Fe3O4@Au composite partially dissociated from the gold foil paper. This led to a decreased Raman intensity response, which showed an obvious negative linear correlation with increasing concentration of EPEC over a wide concentration range from 10 to 107 CFU/mL under an excitation wavelength of 633 nm. The detection limit was about 2.86 CFU/mL in a buffer solution and a licorice extractum and the detection time was only 2.5 h. The results demonstrate that the gold foil paper–based aptasensor can be an excellent biosensing platform that offers a reliable, rapid, and sensitive alternative for EPEC detection.

Paper-based biosensor is one of the most commonly used platforms for point-of-care testing (POCT). Among these platforms, microfluidic paper-based analytical devices (μPADs) have the most versatile designs due to the different hydrophobic barrier patterns and layers of the devices. In addition, μPADs can also be used in combination with other biosensor platforms to improve the performance of the device. Simple and convenient methods for fabricating low-cost and design-adjustable hydrophobic barriers on paper are one of the most challenging aspects for creating μPADs. This work demonstrated a simple technique for using the common polylactic acid (PLA) filament and wax filament to create hydrophobic barriers on paper for μPADs using a commercialized 3D printer. As a proof of concept, the papers with 3D printed PLA barrier were used in combination with a fluidic chip in a prototype biosensor, in which the barrier paper housed four cell-free reactions and the fluidic chip achieved sample delivery to the reactions in the device. Our designed prototype was capable of discriminating dengue virus serotypes based on small nucleotide sequence differences. The proposed combination of 3D-printed barrier paper and fluidic chip provides a versatile platform for rapid prototyping of POCT with possible compatibility with various detection systems.

Membrane emulsification is a promising new technique that can be deployed as a scalable modular conduit for the consistent and continuous production of single and complex emulsions. This work reports on the development of a manufacturing platform based on membrane emulsification for the first time for microcapsule-based self-healing cementitious materials. The feasibility of single and double emulsion production with wall formation as a secondary step through UV radical polymerisation was explored using a discrete membrane emulsification dispersion cell. The operational parameters (pressure, dispersed phase flux, temperature, shear rate) were established for the specific phase characteristics (viscosity, density, interfacial tension) to achieve control of emulsion droplets and maintain a high encapsulation of core content (high payload). Microcapsules with sodium silicate core and an average diameter of ∼130 μm were produced. Microcapsules were shown to achieve high payload (∼89%). Moreover their thermal stability was characterised and their release performance in the cementitious matrix established. The results demonstrated the capability of membrane emulsification to produce microcapsules with an aqueous core for use in self-healing of cementitious materials.

Molecularly imprinted polymers are efficient and selective adsorbents which act as artificial receptors for desired compounds with the ability to recognize the size, shape, and functional groups of the compounds simultaneously. A molecularly imprinted polymer is prepared by the polymerization of functional monomers around a template (analyte) molecule. Afterward, the removal of the template from the polymer matrix leaves a selective cavity behind. The fabrication and development of molecularly imprinted polymers grew rapidly, due to their low cost, simple preparation, selectivity, sensitivity, and stable physicochemical properties. Traditionally, molecularly imprinted polymers can be synthesized using two main methods, namely bulk and surface imprinting. For more efficient use of the latter method, researchers have developed molecularly imprinted polymers grafted on the solid-phase matrix (substrate). This grafting technique would be particularly useful for surface imprinting of macromolecules, such as proteins. Cellulose fibers of papers with unique properties such as being abundant, retaining a porous structure, having good adsorption properties, and possessing hydroxyl groups naturally have gained much attention as substrate. The goal of this review is to introduce molecularly imprinted polymer-grafted or molecularly imprinted polymer-coated paper, as an interesting, simple, and efficient method in the detection and separation of small and large molecules. Therefore, in the present paper, several recent preparation techniques and applications of molecularly imprinted polymer-grafted paper are reviewed and discussed in detail. Green, cost-effective, selective, and sensitive paper-based sensor prepared via grafting molecularly imprinted polymer on paper surface with the potential use for online detection trace of analytes in the point-of-care testing.

The development of low cost, portable, and disposable biosensors for equipment-free and naked-eye biosensing is in eager demand for their widespread application in biomedical field, but it is still a challenge. Herein, we propose a novel paper analytical device (PAD) for truly equipment-free and naked-eye biosensing using dopamine as the chromogenic agent based on target-initiated catalyzed oxidation reaction. The dopamine-functionalized PAD (DPAD) possesses a significant three-dimensional net structure, excellent hydrophilicity, and unique response toward G-quadruplex DNAs against other DNAs, benefiting the bio/chemo reaction occurrence to assay target biomolecules. In light of the exceptional properties, the fabricated DPAD was applied in the analysis of Dam MTase through target-triggered exponential isothermal amplification. The recognition and methylation of H1 by Dam MTase contribute to formation of abundant hemin/G-quadruplexes, which catalyze oxidation of dopamine into dopachrome and reduce the dopamine amount on the DPAD surface. In comparison with the case in which Dam MTase is absent, an evident deep pink signal originating from dopachrome is observed directly by the naked eye and relied on Dam MTase concentrations. Therefore, truly equipment-free and naked-eye detection of Dam MTase is achieved with a detection limit of 1.46 U/mL. The fabricated DPAD not only achieves Dam MTase-visualized detection but also permits the accurate determination of other analytes by varying recognizable DNA's sequences, thus offering a universal biosensor and depicting significant potential for widespread applications in biomedical field.

Paper-based microfluidic analytical devices (μPADs) have recently attracted attention as a point-of-care test kit because of their low cost and nonrequirement for external forces. To directly detect biomarkers in whole blood, however, they need to be assembled with a filter such as a plasma separation membrane (PSM) because the color of the blood cells interferes with the colorimetric assay. However, this assembly process is rather complicated and cumbersome, and the fluid does not uniformly move to the detection zone when the adhesion between the paper and PSM is not perfect. In this study, we report a simple three-dimensional (3D) printing method for fabricating PSM-integrated 3D-μPADs made of plastics without the need for additional assembly. In detail, PSM was coated with parylene C to prevent its dissolution from organic solvent during 3D printing. Then, the coated PSM was superimposed on the paper. Detection zones and a reservoir were printed on the paper and PSM via liquid photopolymerization, using a digital light processing printer. The limit of detection of the PSM-integrated 3D-μPADs for glucose in whole blood was 0.3 mM, and these devices demonstrated clinically relevant performance on diabetes patient blood samples. Our 3D-μPADs can also simultaneously detect multiple metabolic disease markers including glucose, cholesterol, and triglycerides in whole blood. Our results suggest that our printing method is useful for fabricating 3D-μPADs integrated with PSM for the direct detection of biomarkers in whole blood.

Despite substantial advances in sensing technologies, the development, preparation, and use of self-testing devices is still confined to specialist laboratories and users. Decentralized analytical devices will enormously impact daily lives, enabling people to analyze diverse clinical, environmental, and food samples, evaluate them and make predictions to improve quality of life, particularly in remote, resource-scarce areas. In recent years, paper-based analytical tools have attracted a great deal of attention; the well-known properties of paper, such as abundance, affordability, lightness, and biodegradability, combined with features of printed electrochemical sensors, have enabled the development of sustainable devices that drive (bio)sensors beyond the state of the art. Their blindness toward colored/turbid matrices (i.e., blood, soil), their portability, and the capacity of paper to autonomously filter/purge/react with target species make such devices powerful in establishing point-of-need tools for use by non-specialists. This protocol describes the preparation of a voltammetric phosphate sensor and an amperometric nerve agent biosensor; both platforms produce quantitative measurements with currents in the range of microamperes. These printed strips comprise three electrodes (graphite for working and counter electrodes and silver/silver chloride (Ag/AgCl) for the reference electrode) and nanomodifiers (carbon black and Prussian blue) to improve their performance and specificity. Depending on analytical need, different types of paper (filter, office) and configurations (1D, 2D, 3D) can be adopted. The protocol, based on the use of cost-effective manufacturing techniques such as drop casting (to chemically modify the substrate surface) and wax/screen printing (for creating the channels and electrodes), can be completed in

Minimally invasive devices to detect molecules in dermal interstitial fluid (ISF) are desirable for point-of-care diagnostic and monitoring applications. In this study, we developed a microneedle (MN) patch that collects ISF for on-patch biomarker analysis by surface-enhanced Raman scattering (SERS). The micrometer-scale MNs create micropores in the skin surface, through which microliter quantities of ISF are collected onto plasmonic paper on the patch backing. The plasmonic paper was prepared by immobilizing poly(styrenesulfonate) (PSS) coated gold nanorods (AuNRs) on a thin strip of filter paper using plasmonic calligraphy. Negatively charged PSS was used to bind positively charged rhodamine 6G (R6G), which served as a model compound, and thereby localize R6G on AuNR surface. R6G bound on the AuNR surface was detected and quantified by acquiring SERS spectra from the plasmonic paper MN patch. This approach was used to measure pharmacokinetic profiles of R6G in ISF and serum from rats in vivo. This proof-of-concept study indicates that a plasmonic paper MN patch has the potential to enable on-patch measurement of molecules in ISF for research and future medical applications.

Paper-based optoelectronic noses (OENs) are being developed based on printing of organic and organometallic reagents on hydrophilic substrates that can visualize the odor of volatiles. In this work, we report for the first time the use of nanoparticles for fabrication of novel paper-based OENs, which represent much higher sensitivity and produce simple but discriminant colorimetric signature of volatile metabolomes. This nano-optoelectronic nose (NOEN) system, which is fabricated by dropping of gold and silver nanoparticles (each synthesized by 8 chemical species) on the paper, gives obvious colorimetric signatures for chemicals having individual or combined functional groups. Owning to their ultrasensitivity, these simple devices need very small amounts of analytes. These devices could detect and discriminate 45 volatile organic compounds in 9 chemical families including phenols, alchohols, ketones, aldehydes, amines, acids, esters, arenes, and hydrocarbons. In addition to excellent discrimination ability, this NOEN sensor shows ultrahigh sensitivity such that could determine volatile compounds with detection limits around or lower than 10 ppb. Moreover, it can be combined with multivariate calibration methods for quantitative analysis of a metabolite in a complex mixture.

Due to the combined advantages of cellulose and nanoscale (diameter 20–60 nm), bacterial cellulose possesses a series of attractive features including its natural origin, moderate biosynthesis process, good biocompatibility, and cost-effectiveness. Moreover, bacterial cellulose nanofibers can be conveniently processed into three-dimensional (3D) intertwined structures and form stable paper devices after simple drying. These advantages make it suitable as the material for construction of organ-on-a-chip devices using matrix-assisted sacrificial 3D printing. We successfully fabricated various microchannel structures embedded in the bulk bacterial cellulose hydrogels and retained their integrity after the drying process. Interestingly, these paper-based devices containing hollow microchannels could be rehydrated and populated with relevant cells to form vascularized tissue models. As a proof-of-concept demonstration, we seeded human umbilical vein endothelial cells (HUVECs) into the microchannels to obtain the vasculature and inoculated the MCF-7 cells onto the surrounding matrix of the paper device to build a 3D paper-based vascularized breast tumor model. The results showed that the microchannels were perfusable, and both HUVECs and MCF-7 cells exhibited favorable proliferation behaviors. This study may provide a new strategy for constructing simple and low-cost in vitro tissue models, which may find potential applications in drug screening and personalized medicine.

Recently, resistance random access memories (RRAMs) have been studied extensively, because the demand for information storage is increasing. However, it remains challenging to obtain a flexible device because the active materials involved need to be nontoxic, nonpolluting, distortion-tolerable, and biodegradable as well adhesive to diverse flexible substrates. In this paper, tannic acid (TA) and an iron ion (FeIII ) coordination complex were employed as the active layer in a sandwich-like (Al/active layer/substrate) device to achieve memory performance. A nontoxic, biocompatible TA-FeIII coordination complex was synthesized by a one-step self-assembly solution method. The retention time of the TA-FeIII memory performance was up to 15 000 s, the yield up to 53 %. Furthermore, the TA-FeIII coordination complex can form a high-quality film and shows stable ternary memory behavior on various flexible substrates, such as polyethylene terephthalate (PET), polyimide (PI), printer paper, and leaf. The device can be degraded by immersing it in vinegar solution. Our work will broaden the application of organic coordination complexes in flexible memory devices with diverse substrates.

The synthesis and employment of volatile toxic compounds as chemical weapons with a large-scale destructive power has introduced a new insidious threat over the last century. In this framework, the development of wearable sensing tools represents a critical point within the security field, in order to provide early alarm systems. Herein, a novel wearable electrochemical biosensor was developed for the rapid and on-site detection of mustard agents. Since a chemical attack is typically carried out by spraying these volatile agents into air, the sensor was designed in order to be able to measure mustard agents directly in the aerosol phase, further than in the liquid phase. The electrodes were screen-printed onto a filter paper support, which allowed to harness the porosity of paper to pre-load all the needed reagents into the cellulose network, and hence to realise an origami-like and reagent-free device. Mustard agent detection was carried out by monitoring their inhibitory effects toward the choline oxidase enzyme, through the amperometric measurement of the enzymatic by-product hydrogen peroxide. A carbon black/Prussian blue nanocomposite was used as a bulk-modifier of the conductive graphite ink constituting the working electrode, allowing for the electrocatalysis of the hydrogen peroxide reduction. After having verified the detecting capability toward a mustard agent simulant, the applicability of the resulting origami-like biosensor was demonstrated for the rapid and real-time detection of real sulfur mustard, obtaining limits of detection equal to 1 mM and 0.019 g·min/m3 for liquid and aerosol phase, respectively.

Microfluidic paper-based analytical devices (μPADs) have recently emerged as a simple, portable, user-friendly, and affordable alternative to more instrument-intensive analytical approaches for point-of-care testing (POCT), food safety analysis, and environmental monitoring. However, most of the existing methods for the fabrication of μPADs still face a great challenge because of different trade-offs among cost, convenience, and the pattern resolution. In this work, we report a facile one-step approach to prepare a μPAD using an affordable, easy-to-build 3D printer to generate patterns of solid wax on laboratory filter paper. The presented wax printing method did not require the use of predesigned masks and an external heat source to form complete hydrophobic wax barrier through the use of a custom-made extruder. The results revealed a strong linear relationship (R2 = 0.985) between the nominal and the printed widths of the wax barriers. The achievable resolution of the wax barrier printed on filter paper was 468 ± 72 µm, which was lower than previously reported minimum barrier feature sizes achieved by wax printing and other wax patterning techniques, such as stamping and screen-printing. The analytical utility of the fabricated μPADs was evaluated for colorimetric nitrite and glucose detection in artificial solutions. It was found that the fabricated μPADs provided adequate accuracy and reproducibility for quantitative determination of nitrite and glucose within concentration ranges relevant to the disease detection in human saliva and urine. The wax printing approach reported here provides a simple, rapid, and cost-effective fabrication method for paper-based microfluidics and may bring benefits to medical diagnostics in the developing world.

In this study, a novel photoluminescence material for the detection of tributyltin (TBT) was developed by using a paper-based nanocomposite system. For this purpose, molecularly imprinted polymeric nanoparticles (MIN) were synthesized with mini-emulsion polymerization technique. Graphene quantum dots obtained by the hydrothermal pyrolysis were immobilized to the nanoparticle surface via EDC-NHS coupling. The fabrication of sensing platform for TBT can be divided into two steps that are the preparation of nanocomposite and the applying the nanocomposite onto nitrocellulose membrane. The selectivity constant and association kinetics were calculated to analyze the interaction of TBT with immobilized MINs. The results proved that the developed nanosensor is promising for the determination of TBT with high selectivity and sensitivity reaching a detection limit of 0.23 ppt in seawater. This novel photoluminescent nanosensor has the potential to pave the way for further studies and applications., Recep Üzek thanks to TUBITAK for the given scholarship. We acknowledge the support from European Commission through the Graphene Flagship Core 2 project and from Ministerio de Economıa, Industria y Competitividad (MINECO), Agencia Estatal de Investigacion (AEI) for the project MAT2017-87202-P. The ICN2 is funded by the CERCA Programme/Generalitat de Catalunya. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV2017-0706).