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Aptamers are short oligonucleotides designed to possess high binding affinity towards specific target compounds (ions, molecules, or cells). Due to their function and unique advantages, aptamers are considered viable alternatives to antibodies as biorecognition elements in bioassays and biosensors. On the other hand, paper-based devices (PADs) have emerged as a promising and powerful technology for the fabrication of low-cost analytical tools, mainly intended for on-site and point-of-care applications. The present work aims to provide a comprehensive overview of paper-based aptasensors. The review describes the fabrication methods and working principles of paper-based devices, the properties of aptamers as bioreceptors, the different modes of detection used in conjunction with aptasensing PADs, and representative applications for the detection of ions, small molecules, proteins, and cells. The future challenges and prospects of these devices are also discussed.

A turn-on fluorescent aptasensor based on a paper-based microfluidic chip was developed to detect arsenite via aptamer competition strategy and smartphone imaging. The chip was prepared by wax-printing hydrophilic channels on filter paper. It is portable, low-cost, and environmentally friendly. Double-stranded DNA consisting of aptamer and fluorescence-labeled complementary strands was immobilized on the reaction zone of the paper chip. Due to the specific strong binding between aptamer and arsenite, the fluorescent complementary strand was squeezed out and driven by capillary force to the detection area of the paper chip, so that the fluorescent signal arose in the detection area under the excitation wavelength of 488 nm. Arsenite can be quantified by using smartphone imaging and RGB image analysis. Under the optimal conditions, the paper-based microfluidic aptasensor exhibited excellent linear response over a wide range of 1 to 1000 nM, with a detection limit as low as 0.96 nM (3σ). [ABSTRACT FROM AUTHOR]

Aptamers are short oligonucleotides designed to possess high binding affinity towards specific target compounds (ions, molecules, or cells). Due to their function and unique advantages, aptamers are considered viable alternatives to antibodies as biorecognition elements in bioassays and biosensors. On the other hand, paper-based devices (PADs) have emerged as a promising and powerful technology for the fabrication of low-cost analytical tools, mainly intended for on-site and point-of-care applications. The present work aims to provide a comprehensive overview of paper-based aptasensors. The review describes the fabrication methods and working principles of paper-based devices, the properties of aptamers as bioreceptors, the different modes of detection used in conjunction with aptasensing PADs, and representative applications for the detection of ions, small molecules, proteins, and cells. The future challenges and prospects of these devices are also discussed. [ABSTRACT FROM AUTHOR]

The use of paper as a smart support in the field of electrochemical sensors has been largely improved over the last 15 years, driven by its outstanding features such as foldability and porosity, which enable the design of reagent and equipment-free multi-analysis devices. Furthermore, the easy surface engineering of paper has been used to immobilize different bioreceptors, through physical adsorption, covalent bonding, and electrochemical polymerization, boosting the fine customization of the analytical performances of paper-based biosensors. In this review, we focused on the strategies to engineer the surface of the paper for the immobilization of (bio)recognition elements (eg., enzymes, antibodies, DNA, molecularly imprinted polymers) with the overriding goal to develop accurate and reliable paper-based electrochemical biosensors. Furthermore, we highlighted how to take advantage of paper for designing smart configurations by integrating different analytical processes in an eco-designed analytical tool, starting from the immobilization of the (bio)receptor and the reagents, through a designed sample flow along the device, until the analyte detection. [ABSTRACT FROM AUTHOR]

Schematic diagram of a multi-channel paper-based aptasensor for the electrochemical detection of four target metal ions. [Display omitted] • An electrochemical chip was developed for real-time detection of multi-target. • The chip was prepared on environmental paper. • The chip was able to detect four metal ions, including both anions and cations. • The chip was ultrasensitive and exhibited superior detection limits at pM level. • This work was successfully applied for the detection of crabs. A paper-based electrochemical chip with multiple channels was developed for rapid and ultrasensitive detection of multiple heavy metals by using an aptamer competition strategy. Automatic screen printing was used to create microfluidic patterns on the chip, where liquid is self-driven by capillary force without pump assistance from central to the detection areas. When target ions are present in samples, the methylene blue-modified aptamers dissociate from their complementary sequences immobilized on the chip, resulting in a change in the electrochemical signal. Under optimized experimental conditions, the multi-channel paper-based platform demonstrates a wide linear relationship ranging from 10 pmol/L to 1000 nmol/L. The detection limits for Pb2+, Cd2+, AsO 2 −, and Hg2+ were as low as 1.55 pmol/L, 0.84 pmol/L, 1.18 pmol/L and 1.63 pmol/L (3σ), respectively, indicating excellent selectivity. The sensor was successfully utilized to detect four distinct heavy metal ions in crab meat with a recovery rate between 84.79 % and 101.55 %. [ABSTRACT FROM AUTHOR]

A simple multipath paper-based device was designed for ultrasensitive detection of kanamycin using quencher-free 2-aminopurine fluorescence probe and exonuclease I. [Display omitted] • A multipath paper-based device was designed for ultrasensitive and rapid detection of kanamycin. • Quencher-free 2-aminopurine fluorescence probe was used as detection signal source. • Employment of high hydrolysis properties of exonuclease I toward single stranded DNA. • A synergistic effect of 2-aminopurine and exonuclease I enhanced the sensitivity. A quencher-free multipath microfluidic paper-based analytical device (µPAD) was constructed for ultrasensitive detection of kanamycin based on exonuclease I (Exo I)-assisted signal enhancement of 2-aminopurine (2-AP). Here, Exo I, a single-stranded DNA-specific nuclease, was introduced to fully liberate 2-AP mononucleotides to greatly enhance biosensing sensitivity. 2-AP, a fluorescent adenine analogue embedded in single-stranded DNA (ssDNA), was employed as the detection signal source. The fluorescence of 2-AP is strong in the mononucleotide state, while it can have low fluorescence and even no fluorescence in ssDNA and dsDNA, respectively. The 2-AP fluorescence probe included 2-AP DNA and kanamycin aptamer. When kanamycin was present, binding occurred between kanamycin and the aptamer, leading to ssDNA, which was further digested by Exo I. In this case, free 2-AP mononucleotides were liberated, indicating strong fluorescence. In addition, the captured kanamycin was released for binding with the new aptamer, which resulted in the formation of a binding-hydrolysis-release cycle with the aid of Exo I. Under optimal conditions, this µPAD exhibited sensitive and multipath detection of kanamycin at concentrations as low as 1.26 × 10−14 M with a wide range of 10−13–10−7 M. Furthermore, satisfactory results were achieved for analysing spiked kanamycin in milk and honey samples. This strategy is a very promising tool for monitoring antibiotics and evaluating the safety of animal-derived foods. [ABSTRACT FROM AUTHOR]

In this work, a paper‐based electrochemical aptamer sensor was developed for the detection of aflatoxin B1 (AFB1) using a combination of MXene–Ti3C2Tx and nucleic acid aptamers. The prepared single‐layer or few‐layer MXene suspension is suction‐filtered onto MXene paper, which is cut to prepare MXene electrodes. To accomplish AFB1 specific detection, an amino‐labeled AFB1 aptamer is mounted on the surface of the carboxy‐functionalized MXene electrode. When AFB1 is present, it particularly binds to the aptamer to form a 3D structure, reducing the efficiency of electron transmission on the sensor surface. The difference in impedance signal change at the electrode/electrolyte interface is used to quantify AFB1. The results indicated that the detection range is 0.05–100 ng/mL, the detection limit is 0.04 ng/mL, and the recovery rate of AFB1 in corn samples is 97.8%–111.52% with the optimal detection conditions. The MXene paper‐based label‐free aptasensor is versatile and can detect different targets by simply swapping out the aptamers of different targets. The sensor also has a wide range of applications in food analysis and environmental testing. Practical applications: A paper‐based electrochemical aptamer sensor was developed to detect aflatoxin B1 using a combination of MXene–Ti3C2Tx and nucleic acid aptamers.The design is based on the preparation of MXene electrodes by pumping and filtering monolayer or multilayer MXene suspensions onto MXene paper and cutting.The MXene paper‐based label‐free aptamer sensor was designed to be versatile, allowing the detection of different targets by simply replacing the aptamer with one from a different targets. [ABSTRACT FROM AUTHOR]

An aptamer is a synthetic oligonucleotide, referring to a single-stranded deoxyribonucleic acid or ribonucleic acid ligand produced by synthesis from outside the body using systematic evolution of ligands by exponential enrichment (SELEX) technology. Owing to their special screening process and adjustable tertiary structures, aptamers can bind to multiple targets (small molecules, proteins, and even whole cells) with high specificity and affinity. Moreover, due to their simple preparation and stable modification, they have been widely used to construct biosensors for target detection. The paper-based sensor is a product with a low price, short detection time, simple operation, and other superior characteristics, and is widely used as a rapid detection method. This review mainly focuses on the screening methods of aptamers, paper-based devices, and applicable sensing strategies. Furthermore, the design of the aptamer-based lateral flow assay (LFA), which underlies the most promising devices for commercialization, is emphasized. In addition, the development prospects and potential applications of paper-based biosensors using aptamers as recognition molecules are also discussed. [ABSTRACT FROM AUTHOR]

Background: The prevalence and death rate arising from malaria infection, and emergence of other diseases showing similar symptoms to malaria require the development of malaria-specific and sensitive devices for its diagnosis. To address this, the design and fabrication of low-cost, rapid, paper-based analytical devices (µPAD) using surface-immobilized aptamers to detect the presence of a recombinant malarial biomarker—Plasmodium falciparum lactate dehydrogenase (rPfLDH)—is reported in this study. Methods: Test zones on paper surfaces were created by covalently immobilizing streptavidin to the paper, subsequently attaching biotinylated aptamers to streptavidin. Aptamers selectively bound rPfLDH. The measurement of captured rPfLDH enzyme activity served as the means of detecting this biomarker. Enzyme activity across three replicate sensors was digitally quantified using the colorimetric Malstat assay. Results: Screening of several different aptamers reported in the literature showed that aptamers rLDH7 and 2008s immobilized in this manner specifically recognised and captured PfLDH. Using rLDH7, the sensitivity of the µPAD sensor was evaluated and the µPAD sensor was applied for preferential detection of rPfLDH, both in buffered solutions of the protein and in spiked serum and red blood cell lysate samples. In buffered solutions, the test zone of the µPAD sensor exhibited a KD of 24 ± 11 nM and an empirical limit of detection of 17 nM, respectively, a limit similar to commercial antibody-based sensors exposed to rPfLDH. The specific recognition of 133 nM rPfLDH in undiluted serum and blood samples was demonstrated by the µPAD. Conclusion: The reported µPAD demonstrates the potential of integrating aptamers into paper-based malarial rapid diagnostic tests. [ABSTRACT FROM AUTHOR]

At present, most reported studies on paper-based sensing devices for food-borne pathogens usually rely on a single signal as the basis for judging the results, accompanied with inaccurate detection results. In this study, we used the lanthanide MOFs being covalently modified with aptamers (Apt-LnMOFs) as the sensing and recognition element of Vibrio parahaemolyticus (VP), and the paper-based needle shape device (paper-needle) as the visual signal output carrier. Finally, an accurate detection strategy for VP was successfully constructed. In terms of signal output, the two signal styles of Apt-LnMOFs diffusion distance on the paper-needle and R value (measured by the RGB analysis software of smartphone) are coupled to jointly improve the accuracy of detection results. The method is simple and fast, and the detection accuracy in real samples is 91%. This strategy is very suitable for on-site rapid detection of pathogens, and does not require large professional instruments. [Display omitted] • This method does not require the aid of instruments and professional operation. • The samples can be automatically diffused on the paper-needle device. • The coupled dual-signal jointly improved the accuracy of detection results. • Hand-held paper-needle pathogen analysis device is easy to use and inexpensive. [ABSTRACT FROM AUTHOR]

A new esterase gene est906 was identified from paper mill wastewater sediments via a function-based metagenomic approach. The gene encoded a protein of 331 amino acids, that shared 86% homology with known esterases. Based on the results of multiple sequence alignment and phylogenetic analysis, it was confirmed that Est906 contained a characteristic hexapeptide motif (G-F-S-M-G-G), which classified it as a lipolytic enzyme family V protein. Est906 displayed the highest hydrolysis activity to ρ-nitrophenyl caproate (C6), and its optimal temperature and pH were 54 °C and 9.5, respectively. Additionally, this enzyme had good stability under strong alkaline conditions (pH 10.0–11.0) in addition to moderate heat resistance and good tolerance against several metal ions and organic solvents. Furthermore, a specific nucleic acid aptamer (Apt1) bound to Est906 was obtained after five rounds of magnetic bead SELEX screening. Apt1 displayed high specific recognition and capture ability to Est906. In conclusion, this study not only identified a new esterase of family V with potential industrial application by metagenomic technology but also provided a new method to purify recombinant esterases via nucleic acid aptamers, which will facilitate the isolation and purification of target proteins in the future. [ABSTRACT FROM AUTHOR]

• A distance-based paper sensor for the detection of DNase I is developed. • The quantitative detection of DNase I is achieved by measuring the watermark on the indicator paper. • This method exhibits the advantages of the aptamer-mediated enzyme cascade reaction, low-cost, and label-free detection. DNase I is proven to be an early predictive molecule for a variety of diseases, which is important for early diagnosis and clinical detection of diseases. Herein, we demonstrate a distance-based paper sensor to detect DNase I via an enzymatic cascade reaction mediated by the thrombin aptamer. In the presence of DNase I, the thrombin is able to clot the plasma normally because the aptamer chain is hydrolyzed by DNase I and cannot bind thrombin properly to inhibit thrombin activity. The concentration of DNase I is negatively correlated with the volume of mobile phase in sample solution, and it can be quantified by measuring the flow distance of water on the pH indicator strip. The distance-based paper sensor has good specificity, and the detection limit is 2 × 10−2 U/mL. In addition, it can be used for DNase I analysis in human serum samples to show its efficacy in the early diagnosis of diseases associated with DNase I activity. Overall, we developed a simple, fast and low-cost DNase I detection method, which has great commercial potential. [ABSTRACT FROM AUTHOR]

An ultra-sensitive paper-based molecularly imprinted sensor for detection of H5N1 was described. The results can not only be detected quantitatively by fluorescence, but also can be directly read with naked eyes under visible light or ultraviolet light within 10 min. With naked eye detection, its sensitivity is obviously better than that of commercial kits. In particular, the cost of the sensor is cheap (Original size: RMB 1.53 Yuan each; Smaller size: RMB 0.08 Yuan each), which is beneficial to application. [Display omitted] • Paper-based molecularly imprinted sensor; • Ultra-sensitive detection of H5N1 (LOD, 0.58 fM); • Rapid visual detection of influenza H5N1 within 10 min; • More intuitive and sensitive results than commercially available kit; • Low cost (Original size, 1.53 yuan/piece; Smaller size, 0.08 yuan/piece). The rapid detection of pathogens is important to the control of epidemics. Here, a paper-based molecularly imprinted sensor has been developed for the visual detection of influenza H5N1 virus. Firstly, the paper-based molecularly imprinted was prepared by a sol–gel reaction. Then, H5N1 ∼ Apt was covalently bound to the surface of the ZIF-8-NH 2 coated with rhodamine B (RhB) through an amide bond, to produce the fluorescent and colorimetric probe ZIF-8-NH 2 @RhB ∼ Apt. When H5N1 and ZIF-8-NH 2 @RhB ∼ Apt are added to the paper-based MIPs, the H5N1 will be combined with MIPs through the synergistic effects of shape and size compatibility and interaction with the functional groups of the monomers, and ZIF-8-NH 2 @RhB ∼ Apt will bind to H5N1 through its aptamers to form a sandwich structure. The sensor has ultra-high sensitivity and the detection limit is 0.58 fmol/L by using fluorescence spectroscopy. A semi-quantitative signal can also be observed with the naked eye within 10 min. A comparative study showed that direct visual detection was highly reliable, and the sensitivity was better than that achieved with a commercially available kit. Importantly, the paper-based sensor is low in produce cost (Original size: RMB 1.53 Yuan each; Smaller size: RMB 0.08 Yuan each) and is easy to cut, store and carry. This sensor is expected to allow self-service, visual, high-throughput, and real-time virus detection, which is of great significance for epidemic prevention and control. [ABSTRACT FROM AUTHOR]

There is growing interest in developing printable paper sensors to enable rapid testing of analytes for environmental, food safety, and clinical applications. A major challenge is to find suitable bioinks that are amenable to high-speed printing and remain functional after printing. We report on a simple and effective approach wherein an aqueous ink composed of megadalton-sized tandem repeating structure-switching DNA aptamers (concatemeric aptamers) is used to rapidly create patterned paper sensors on filter paper by inkjet printing. These concatemeric aptamer reporters remain immobilized at the point of printing through strong adsorption but retain sufficient segmental mobility to undergo structure switching and fluorescence signaling to provide both qualitative and quantitative detection of small molecules and protein targets. The convenience of inkjet printing allows for the patterning of internally referenced sensors with multiplexed detection, and provides a generic platform for on-demand printing of sensors even in remote locations. [ABSTRACT FROM AUTHOR]

Electrochemical aptamer‐based (E‐AB) sensors offer a powerful and general means for analyte detection in complex samples for various applications. Paper‐based E‐AB sensors could enable portable, low‐cost, and rapid detection of a broad range of targets, but it has proven challenging to fabricate suitable three‐electrode systems on paper. Here, we demonstrate a simple, economic, and environmentally friendly strategy for fabricating aptamer‐modified paper electrochemical devices (PEDs) via ambient vacuum filtration. The material, shape, size, and thickness of the three‐electrode PED system can be fully customized. We developed aptamer‐modified PEDs that enable sensitive and specific detection of small molecules in minimally processed biosamples. The sensitivity and stability of the PEDs are comparable to E‐AB sensors based on commercial gold electrodes. We believe our strategy can lead to the development of high performance PEDs for the on‐site detection of a variety of analytes. [ABSTRACT FROM AUTHOR]

Enzyme-inorganic hybrid nanoflowers (HNFs) have shown excellent sensing capabilities due to their large specific surface area as well as the simplicity and mildness of the preparation process. However, coupling HNFs to electrodes to fabricate a uniform and controllable enzymatic electrochemical sensing interface remains a challenge. Here, we proposed an aptamer-induced in-situ fabrication strategy for preparing an HNF-based electrochemical sensor with ideal performance. Central to this strategy is the introduction of acetylcholinesterase (AChE)-specific binding aptamer (Apt), which induces the in-situ growth of AChE-copper phosphate (Cu3(PO4)2) HNFs on the surface of carbon paper (CP). In addition, a dense gold nanoparticle (AuNP) layer was electrodeposited on the CP for anchoring Apt and further extending the electroactive surface area. The prepared AChE-Cu3(PO4)2 HNF/Apt/AuNP/CP biosensor exhibited a wide detection range from 1 to 107 pM for the four organophosphorus inhibitors, including isocarbophos, dichlorvos, methamidophos, and parathion, with detection limits down to 0.016, 0.028, 0.071, and 0.113 pM, respectively. With the reactivation of pralidoxime chloride, the electrode can still recover 98.1% of the response after five times of repeated use. In real sample detection, the biosensor achieved high recoveries from 96.45% to 100.13%. The detection target may be extendable to other AChE inhibitors (e.g., drugs for Alzheimer's disease). This study demonstrates for the first time the feasibility of using aptamers as an inducer to fabricate an electrochemical enzyme sensing interface in-situ. This strategy can be used to fabricate other enzyme-based biosensors and therefore has broader applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • WS2 nanotubes (NTs) were successfully prepared to modify the conductive paper electrode. • The modified electrode was implemented in the electrochemical detection of IFN-ɣ. • The modified electrode possessed a picomolar level of detection (LOD) and higher sensitivity with a wider linear range. • The practical feasibility exemplifies a recovery percentage in real samples analysis. Interferon-Gamma (IFN-ɣ), a measurable biomarker is known to be related to Tuberculosis which is one of the major sanitation issues in the world. It is also a crucial indicator of the immune response to many infections and diseases. Measuring the concentration of IFN-γ can assist in disease diagnosis. Therefore, we have developed a cost-efficient, disposable, and highly sensitive paper-based electrochemical biosensor with probing aptamer immobilization that can detect IFN-ɣ with high sensitivity and selectivity. WS 2 nanotubes (NTs) were modified on the nanocomposite conductive paper electrode to provide a large surface area, facilitating the efficient recognition of aptamer with IFN-ɣ, and yielded a high resistance to adsorption of non-targeted molecules. The step-wise modification of the sensing surface was characterized and then the electrode was examined by using differential pulse voltammetry (DPV) in different concentrations of IFN-ɣ samples. The peak current generated by the proposed sensor demonstrated a linear range from 3.125 to 100 pg mL−1, and the detection limit for IFN-ɣ was determined to be 1.13 pg mL−1. Moreover, this novel WS 2 NTs enhanced nanocomposite conductive paper-based electrochemical biosensor was qualified to successfully measure IFN-ɣ in human serum samples, demonstrating its potential application as an efficient tool for Tuberculosis diagnosis. [ABSTRACT FROM AUTHOR]

Inspired by the design of folding greeting cards and tissue drawing covers, a photoelectrochemical (PEC) lab-on-paper device with a controllable fluid separator, producing both reaction zone and detection zone, was explored for ultrasensitive detection of adenosine 5′-triphosphate (ATP) via mimic peroxidase-transfer enhancement of photocurrent response. To realize it, the DNA1, aptamer, and DNA2 as well as the mimic peroxidase of G-quadruplex/hemin modified Au nanocubes were linked on the graphene oxide-functionalized reaction zone via the DNA hybridization. Meanwhile, three-dimensional CuO nanoflowers (CuO NFs) as a photoactive material with outstanding electron transfer ability and absorption of light were grown in situ on the detection zone, providing a PEC active interface. Besides, an innovative fluid separator was elaborately designed by assembling a strip of paper with a hydrophilic channel, providing an effective way to bridge the gap between the two zones with a controllable drawing way, which could successfully avoid the signal interference caused by modifying biomolecules layer by layer on photosensitive materials. In the presence of ATP, the G-quadruplex/hemin modified in the reaction zone was dissociated due to the specific recognition of ATP with aptamer and released into the detection zone with the assistance of controllable fluid separator. The free G-quadruplex/hemin could catalyze hydrogen peroxide to generate oxygen for the consumption of photo-induced electrons from CuO NFs, which could further promote the electron-hole carriers separation efficiency, and eventually resulting in the enhancement of PEC signal. The proposed PEC lab-on-paper device could be employed for specific detection of ATP in the range from 5.0 to 3.0 × 103 nM with a detection limit of 2.1 nM. • The CuO nanoflowers were grown in situ on rGO-modified detection zone. • The lab-on-paper microfluidic systems simplify the analytical processes. • The modification of biomolecules was separated from the PEC transducer. • The fluid separator was designed as a bridge between two functional zones. • The device was applied to detect ATP with high sensitivity, stability and selectivity. [ABSTRACT FROM AUTHOR]

We developed a modified paper spray ionization (PSI) platform, named as paper cone spray ionization (PCSI), for direct mass spectrometric analysis of raw solid samples. The major modification from conventional PSI was the geometry of the paper base: PCSI uses a triangular-pyramidal-shaped paper tip instead of a planar triangular-shaped one. This three-dimensional paper cone serves as a sample container, an in situ solid–liquid extraction chamber, an analyte transport channel, as well as an electrospray tip. Unlike conventional PSI mass spectrometry (MS), a weighing paper with relatively low permeability was found to be more suitable for PCSI MS than other papers. PCSI MS rapidly generated major chemical fingerprints from various solid materials including powdered tablets as well as raw and processed food materials without any sample pre-treatment. [ABSTRACT FROM AUTHOR]

A paper-based SERS test strip combining strengths of paper chip and Raman active substrate was demonstrated to overcome challenges in spectroscopic sensing of complicated samples and realize quantitative detection of disease markers in whole blood. The precisely controlled Au NPs were not only capable of generating condensed hot spots on the fibers, but also enhanced the size exclusion effect of paper, resulting in the novel performance on both SERS detection and sample pretreatment. A biosensor for Mucin-1 is developed by equipping the Au NPs with aptamer. Combining all these merits, this small, cheap and portable test strip might find wide application in clinical diagnosis and health evaluation. [ABSTRACT FROM AUTHOR]

Developing portable and sensitive biosensors for bacteria detection is highly demanded due to their association with environmental and food safety. Paper-based microfluidic chip is the suitable candidate for constructing pump-free biosensor since paper is hydrophilic, low-cost and easy to use. However, the contradiction between sensitivity and small sample volume seriously affects the application of paper-based chip for bacteria detection. Here, a new microfluidic biosensor, combining large PDMS reservoir for sample storage, hydrophilic paper substrate for pump-free water transport, coated microspheres for bacteria capture and super absorbent resin for water absorption, is designed for the detection of bacteria in aqueous samples. Once the sample solution is introduced in the reservoir, water will automatically flow through the gaps between microspheres and the target bacteria will be captured by the aptamer coated on the surface. To facilitate PDMS reservoir bonding and ensure water transport, the upper side of paper substrate is coated with Polyethylenimine modified PDMS and the bottom side is kept unchanged. After all the solution is filtrated, fluorescent dye strained bacteria are enriched on the microspheres. The fluorescent intensity representing the number of bacteria captured is then measured using a portable instrument. Through the designed microfluidic biosensor, the bacteria detection can be achieved with 2 mL sample solution in less than 15 min for water or 20 min for diluted milk. A linear range from 10 CFU/mL to 1000 CFU/mL is obtained. The paper-based 3D biosensor has the merits of low-cost, simple operation, pump-free and high sensitivity and it can be applied to the simultaneous detection of multiple bacteria via integrating different aptamers. [Display omitted] • A microfluidic chip is constructed for detecting bacteria with LOD of 10 CFU/mL. • A funnel-like PDMS reservoir is integrated for large sample solution storage. • Partially permeable paper and super absorbent resin are for self-pumping. • The target bacteria can be captured and enriched by coated microparticles. [ABSTRACT FROM AUTHOR]

In this article, we describe a facile method named as Rubik's Cube stamping (RCS) for equipment-free fabrication of microfluidic paper-based analytical devices (μPADs). RCS is inspired by the worldwide ubiquitous RC toy and requires no specialized electric equipment other than a classical six-faced RC that is assembled with home-made small iron components. It can pattern various rosin microstructures in paper simply by either using different functional faces of the modified RC or applying its internal pivot mechanism to adjust the components’ patterning forms on one functional face. Such a versatile stamping method is quite simple and inexpensive, and thus holds potential for producing rosin-patterned μPADs by untrained users in resource-limited environments such as small laboratories and private clinics, or even at home and in the field. Moreover, a set of one-channel devices are fabricated to design a point-of-care aptamer-based assay with near sample-in–answer-out capability that integrates enzymatic reactions for robust yet efficient signal amplification and a personal glucometer for portable, user-friendly, rapid and quantitative readout. Its utility is well demonstrated with the sensitive and specific detection of adenosine as a model target in buffer samples and undiluted human urine within several minutes. With the advantages of low cost, simplicity, portability, rapidity, and aptamer variety, this general point-of-care assay system reported here may find broad applications including home healthcare, field-based environmental monitoring or food analysis and emergency situations. [ABSTRACT FROM AUTHOR]

In this work, we report a rapid, facile, portable, disposable and low-cost fluorescence and visual method for multiplexed monitoring of cancer cells using graphene oxide (GO)-based aptameric nanosensor in microfluidic paper-based analytical devices. This method has combined the exceptional quenching capability of GO and an aptamer with high specificity and affinity employed as the molecular recognition element. The quantum dots coated mesoporous silica nanoparticles labeled aptamers in a flexible single stranded state could be adsorbed on the surface of GO, and the fluorescence was quenched via Förster resonance energy transfer, with subsequent recovery of the fluorescence upon addition of target cells. Furthermore, the design of sensors for other cancer cells only requires change in the recognition element for the target cell and different colored quantum dots. More importantly, three different cancer cells can be simultaneously determined with a single excitation light. The sensitivity and selectivity of this method for GO-based sensing were extremely high. The color changes could be clearly monitored with the naked eye. And their linear range were from 180 to 8 × 10 7 , 210 to 7 × 10 7 , 200 to 7 × 10 7 cells mL −1 and detection limit were 6270 and 65 cells mL −1 for MCF-7, HL-60, and K562 cells, respectively. It could be applied in clinical sample analysis with a satisfactory result. Therefore, GO-based aptameric nanosensor is highly promising for potential applications in the sensitive monitoring of multiple cancer cells for biomedical research and medical diagnostics. [ABSTRACT FROM AUTHOR]

A selective thin-film microextraction based on aptamer immobilized on cellulose paper was used as a paper spray ionization source for ion mobility spectrometry (PSI-IMS), for the first time. In this method, the paper is not only used as an ionization source but also it is utilized for the selective extraction of analyte, based on immobilized aptamer. This combination integrates both sample preparation and analyte ionization in a Whatman paper. To that end, an appropriate sample introduction system with a novel design was constructed for the paper spray ionization source. Using this system, a continuous solvent flow works as an elution and spray solvent simultaneously. In this method, analyte is adsorbed on a triangular paper with immobilized aptamer and then it is desorbed and ionized by elution solvent and applied high voltage on paper, respectively. The effects of different experimental parameters such as applied voltage, angle of paper tip, distance between paper tip and counter electrode, elution solvent type, and solvent flow rate were optimized. The proposed method was exhaustively validated in terms of sensitivity and reproducibility by analyzing the standard solutions of codeine and acetamiprid. The analytical results obtained are promising enough to ensure the use of immobilized aptamer paper-spray as both the extraction and ionization techniques in IMS for direct analysis of biomedicine. [ABSTRACT FROM AUTHOR]

Abstract: Micrometer‐sized functional nucleic acid (FNA) superstructures (denoted as 3D DNA) were examined as a unique class of biorecognition elements to produce highly functional bioactive paper surfaces. 3D DNA containing repeating sequences of either a DNA aptamer or DNAzyme was created from long‐chain products of rolling circle amplification followed by salt aging. The resulting 3D DNA retained its original spherical shape upon inkjet printing and adhered strongly to the paper surface via physisorption. 3D DNA paper sensors showed resistance to degradation by nucleases, suppressed nonspecific protein adsorption, and provided a much higher surface density of functional DNA relative to monomeric FNAs, making such species ideally suited for development of paper‐based biosensors. [ABSTRACT FROM AUTHOR]

Abstract: We report a paper‐based aptasensor platform that uses two reaction zones and a connecting bridge along with printed multifunctional bio/nano materials to achieve molecular recognition and signal amplification. Upon addition of analyte to the first zone, a fluorescently labelled DNA or RNA aptamer is desorbed from printed graphene oxide, rapidly producing an initial fluorescence signal. The released aptamer then flows to the second zone where it reacts with printed reagents to initiate rolling circle amplification, generating DNA amplicons containing a peroxidase‐mimicking DNAzyme, which produces a colorimetric readout that can be read in an equipment‐free manner or with a smartphone. The sensor was demonstrated using an RNA aptamer for adenosine triphosphate (a bacterial marker) and a DNA aptamer for glutamate dehydrogenase (Clostridium difficile marker) with excellent sensitivity and specificity. These targets could be detected in spiked serum or feacal samples, demonstrating the potential for testing clinical samples. [ABSTRACT FROM AUTHOR]

The authors describe a rapid and highly sensitive point-of-care device for rapid determination of noroviruses, a leading cause of acute gastroenteritis. The assay is based on the use of a norovirus-specific aptamer labeled with 6-carboxyfluorescein, and of multi-walled carbon nanotubes (MWCNT) and graphene oxide (GO). The fluorescence of the 6-FAM labeled aptamer is quenched by MWCNT or GO. In the presence of norovirus, fluorescence is recovered due to the release of the labeled aptamer from MWCNT or GO. An easy-to-make paper-based microfluidic platform was developed using a nitrocellulose membrane. The quantitation of norovirus was successfully performed. The linear range extends from 13 ng·mL to 13 μg·mL of norovirus. The detection limits are 4.4 ng·mL and 3.3 ng·mL, respectively, when using MWCNT or GO. The device is simple and cost-effective, and holds the potential of rapid in-situ visual determination of noroviruses with remarkable sensitivity and specificity. Hence, it provides a new method for early identification of norovirus and a tool for early intervention when preventing the spread of an outbreak. [ABSTRACT FROM AUTHOR]

Lead ion (Pb2+) is one of the most toxic and widely polluted heavy metal ions. Given the potential health risks and economic losses associated with Pb2+, the rapid detection of Pb2+ using fluorescent aptasensors is of significant importance in evaluating food safety. A rapid, facile and economic fluorescent aptasensor using convenient paper as the sensing substrate was designed to high-throughput detect Pb2+ in complex samples within about 45 min. The Pb2+ changed the conformation of FAM-modified Apt from a random coil to a stable G-quadruplex structure. And then Dabcyl-labeled cDNA was added to form double-stranded DNA with the Apt that did not form a G-quadruplex structure, resulting in a weak fluorescence due to the fluorescence resonance energy transfer (FRET). The fluorescent aptasensor showed a positive correlation with Pb2+ concentration, and a linear relationship was obtained in the range of 0.01–10 μM with LOD of 6.1 nM. In addition, this method has been successfully used for the determination of Pb2+ in water, soil and various foods containing complex substrates. Meanwhile, the high-throughput detection of Pb2+ has also reached an acceptable level. Therefore, this convenient strategy has potential application value for on-site rapid detection of Pb2+. A high-throughput paper-based fluorescent aptasensor was successfully developed based on the selectivity of aptamer and paper-supported analytical devices. It can detect Pb2+ in multiple real samples (water-soil-food). The strategy has great application prospect for on-site rapid detection. [Display omitted] • High-throughput paper-based FRET aptasensor was successfully developed and used for lightly Pb2+ detection. • Detection of Pb2+ was achieved in a range of 0.01–10 μM with the LOD of 6.1 nM. • The designed strategy was successfully used in the inspection of multiple real samples (water-soil-food). [ABSTRACT FROM AUTHOR]

The article announces the research articles and reviews that won the "International Journal of Molecular Sciences" Best Paper Award for 2017 including "A RNA-DNA Hybrid Aptamer for Nanoparticle-Based Prostate Tumor Targeted Drug Delivery," "Telomeres, NAFLD and Chronic Liver Disease," and "The Functions of Metallothionein and ZIP and ZnT Transporters: An Overview and Perspective."

Ochratoxin A (OTA) is the most common mycotoxin contaminant that is widely distributed in food products. Herein, a sensitive and rapid sensing platform was constructed based on triple-helix molecular switch and CMC-EDC/NHS covalent immobilized paper. The aptamer-based triple-helix molecular switch (THMS) released signal transduction probe (STP) upon the addition of OTA, which was then enriched on the TR512-peptide functionalized paper modified with CMC-EDC/NHS chemistry. The sensing platform achieved a lower detection limit of 0.012 ng/mL with the linear range of 0.025–100 ng/mL. Notably, the sensing could be finished in less than 15.5 min without complex concentration process or expensive equipment. Additionally, the TR512-peptide based fusion protein was strongly-immobilized on the paper substrate via carbodiimide coupling, which prevented the fusion protein from leaching and enabled a large amount of solution molecules to bind with the fusion protein (up to 1 mL). Finally, a full-set of device was developed and applied in real samples with good accuracy. Taken together, the sensing platform integrating THMS with functionalized paper possesses practical application prospects in food samples and may offer a new protocol for the detection of multifarious target analytes by virtue of altering the aptamer sequence in THMS. [Display omitted] • The dexterous combination of the triple-helix molecular switch and CMC-EDC/NHS covalent immobilized paper. • Low time-consumption : less than 15.5 min without complex concentration process or expensive equipment usage. • A sensitive OTA determination platform: a detection limit of 0.012 ng/mL with the range of 0.025–100 ng/mL. • CMC-EDC/NHS covalent immobilized paper enabled a large amount of solution molecules to flow through (up to 1 mL). • General applicability : variable aptamer sequence in the loop without redesigning the triple-helix structure. [ABSTRACT FROM AUTHOR]

Electrochemical sensing technology integrated with a paper-based analytical device (PAD) offers an effective method for analyte detection. Nevertheless, it is still challenging to realize reliable and sensitive analysis owing to the basic shortcomings (inferior conductivity and high batch-to-batch variability) of paper-based working electrodes (WE) and lack of efficient signal amplification label. Herein, we proposed a novel electrochemical aptasensor to detect ochratoxin A (OTA), with MXene-Au as sensing substrates and Pt nanoparticles (NPs) anchored hollow structure NiCo-layered double hydroxides (Pt@NiCo-LDH) as signal amplification materials. The complementary DNA (cDNA) was firstly assembled onto the MXene-Au/WE via Au-S bonds. Then aptamer (apta)-binding Pt@NiCo-LDH with excellent peroxidase (POD)-like activity was immobilized through hybridization to trigger the "signal on" state, generating a significant electrochemical signal. The presence of OTA enabled the dissociation of the apta-cDNA hybrid, releasing signal amplification labels to achieve "signal off" state. Based on the "signal on/off" strategy, the aptasensor exhibited a wider linear range from 20 fg/mL to 100 ng/mL and a lower limit of detection of 8.9 fg/mL (S/N = 3). This work provided a new avenue for the versatile design of electrochemical paper-based platform that enabled the on-site detection of various analytes. [Display omitted] • Mxene-Au as sensing substrates exhibited high conductivity, good stability and low batch-to-batch variation. • Pt@NiCo-LDH showed excellent peroxidase-like catalytic activity and high durability to environmental conditions. • The electrochemical OTA aptasensor based on "signal on/off" strategy showed a wider linear and a lower limit of detection. • This work provided a new avenue for broad spectrum detection of analytes by simply altering the specific aptamer. [ABSTRACT FROM AUTHOR]

A novel tetrahedral DNA nanostructure (TDN) functionalized paper-based colorimetric sensor was developed for ultrasensitive analysis of mercury ion (Hg2+). On the paper-based platform, TDN was used as scaffold to anchor aptamer to improve the capture efficiency owing to the controllably specific orientation, low steric hindrance effect and well-defined spacing. In the absence of Hg2+, biotinylated aptamer would bind with streptavidin-labeled HRP. Whereas, in the presence of Hg2+, aptamer would preferentially bind to Hg2+ owing to the higher binding constant of T–Hg–T than that of T–A, which consequently leading to the biotinylated aptamer releasing from TDN. After introducing TMB-H 2 O 2 solution, strong variation of color signal could be observed. Therefore, the quantitative analysis of Hg2+ was carried out by using smartphone to monitor the color intensity on paper chip. The proposed strategy exhibits good linearity over a wide range of 10–13–10–7 M with a low detection limit of 30 fM. And this method had been successfully applied in real water samples. Our strategy provided a versatile, low-cost and user-friendly paper-based monitoring platform for rapid and ultrasensitive analysis of heavy metal ions and thus had potential applications in food safety and public health. [Display omitted] • A sensitive paper-based platform based on tetrahedral DNA nanostructure. • DNA nanostructure confers controllable anchoring aptamer in a consistently specific orientation and well-defined spacing. • Employment of high affinity of aptamer toward target mercury ion with 30 fM detection limit. • The developed platform is simplicity, rapidity, user-friendly, low cost and sensitive monitor food quality. [ABSTRACT FROM AUTHOR]

This work initially describes the design of low-cost, naked-eye quantitative aptamer-based assays by using microfluidic paper-based analytical device (μPAD). Two new detection motifs are proposed for quantitative μPAD measurement without using external electronic readers, which depend on the length of colored region in a strip-like μPAD and the number of colorless detection microzones in a multi-zone μPAD. The length measuring method is based on selective color change of paper from colorless to blue–black via formation of iodine–starch complex. The counting method is conducted on the basis of oxidation–reduction reaction between hydrogen peroxide and potassium permanganate. Their utility is well demonstrated with sensitive, specific detection of adenosine as a model analyte with the naked eye in buffer samples and undiluted human serum. These equipment-free quantitative methods proposed thus hold great potential for the development of more aptamer-based assays that are simple, cost-efficient, portable, and user-friendly for various point-of-care applications particularly in resource-constrained environments. [ABSTRACT FROM AUTHOR]

A paper-based portable and disposable cyto-device was fabricated for the purpose of detecting cancer cells and in-situ screening of anticancer drugs. The device was prepared as follows: (a) Au@Pd paper electrodes were prepared by growing Au@Pd nanoparticles on cellulose; (b) the aptamer against MCF-7 cells was immobilized on the paper electrodes; (c) PtNi alloy particles were loaded with carbon dots to form a PtNi@C-dot composite acting as the ECL label, (d) concanavalin A (Con A) was labeled with the ECL label and then dropped on sensor surface carrying cancer cell. Con A can specifically recognize the mannose on the cancer cell surface. The assay is performed in the following way: (1) The aptamer-modified electrode is placed in a solution containing MCF-7 cancer cells; (2) buffer containing peroxodisulfate is added; (3) a potential sweep (from −0.5 to −1.8 V) is applied to the electrode, and ECL intensity is recorded. ECL intensity is related to the number of captured MCF-7 cells in the 480 to 2.0 × 10 cells⋅mL‾ concentration range. The electrode was applied to design a screening method for anti-cancer drugs. This is accomplished by monitoring the number of apoptotic cancer cells after exposing the cells on the electrode to a drug-containing medium. In our perception, the method presented here has a wide range of potential applications in cancer diagnosis and treatment. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We report the first portable upconversion nanoparticles (UCNPs)-based paper device for road-side field testing of cocaine. Upon the recognition of cocaine by two pieces of rationally designed aptamer fragments, the luminescence of UCNPs immobilized on the paper is quenched by Au nanoparticles (AuNPs), which indicates the cocaine concentration. This device can give quantitative results in a short time with high sensitivity using only a smartphone as the apparatus. Moreover, this device is applicable in human saliva samples, and it also can be used to monitor the cocaine content change in blood samples. The results of this work demonstrate the prospect of developing UCNPs-based paper devices for field testing of drug abuse. [ABSTRACT FROM AUTHOR]

Aptamers and DNA nanostructures are both increasingly attractive tools for application in medicine and biology. DNA nanotechnology permits engineering of biocompatible, nanoscale structures with near atomic-scale resolution, whilst aptamers provide unique biorecognition and targeting properties as malleable ligands. Crucially, as both toolsets are nucleic acid-based they can be readily integrated to combine their respective advantages. Aptamers have indeed been used to enhance the functional repertoire and scope for application of DNA nanostructures, yet clear guidelines regarding their integration are difficult to find. In this context, we hereby provide a review of key concepts and proof-of-principle examples for aptamer-integrated DNA nanostructures. A concise three-step strategy is also provided to help demonstrate translation of ideas from concept to actual DNA sequences for nanostructure assembly and aptamer integration. • A three-step strategy for design of aptamer-enabled DNA nanostructures is presented. • Paper origami is used initially to correctly orientate single-stranded DNA. • Known DNA sequences are assigned with reference to aptamer structure. • Sequences are generated for the final DNA nanostructure. • An example of an aptamer-integrated pentagonal pyramid is demonstrated. [ABSTRACT FROM AUTHOR]

Sample pretreatment process is usually performed before real sample detection. Extraction is one of the most prevalent pretreatment methods. Due to the unequal solubility in two liquid phases, target is extracted (usually from water to organic phase) and further detected with laboratory instruments. Although the analytical instruments have high sensitivity and selectivity, they are relatively expensive and require skilful hands, which is restricted to laboratory use. Here, paper-based analytical devices (μPADs) for measuring samples extracted with organic solvents were tested. The μPADs were employed as a filter for buffer exchange, allowing the transfer of targets from organic solvent to water-based buffer, which could be specifically detected by water-based assays. As an example, polychlorinated biphenyls (PCBs) in n-hexane were detected with aptamer and gold nanoparticles (AuNPs) on μPADs within 30 min. The result of colour change can be recognized from 70.0 ng/L with a low loading amount (0.5 μL). Instead of laboratory instrumental analysis with relative high cost, this assay showed the promising utility of μPADs for target detection after sample pretreatment, which could be utilized as a general platform for inexpensive onsite detection. [ABSTRACT FROM AUTHOR]

[Display omitted] • Non-invasive and Invasive Body-fluids. • Frugal detection systems. • Colorimetric, Fluorimetric, SERS, Electro-chemical, Electrophoresis. • Electro-kinetics, Aptamers and body-fluid heterogeneity. Paper has been used for testing analytes since the advent of litmus paper. Also, the rapid growth of the human population in isolated areas of the world have engendered demand for testing and diagnostic methods that are not only easy to transport, but also have a low cost of fabrication and rapid results. Hormones are crucial biomarkers which can be used to detect certain physiological conditions. These hormones, present in non-invasive and invasive body fluids, hold major potential for detection using paper-based devices. This review paper aims to highlight the advancements in the creation of paper-based microfluidic devices to detect hormones in different body fluids. It exhaustively explains the current methods of detection for hormones in various body fluids like sweat, saliva and serum using paper-based microfluidic devices and the role of these devices in the future in terms of rapid detection, low cost, and ease of transport. By demonstrating the mechanisms of these devices, this paper shows a promising unconventional avenue for efficient hormone detection. [ABSTRACT FROM AUTHOR]

Water quality monitoring is of great significance for human health, which involves a large number of distinct targets detection, such as pathogens, heavy metal ions, and toxins. Traditional detection methods usually carried out in well-equipped central labs are subjected to time, labor, and expense consumption, thus not suitable for implementing water quality monitoring at point of care, where the detection implemented on a multiplexed, miniaturized, and simplified device with rapid and sensitive answer out is desired. To this end, we developed a paper disc relying on upconversion fluorescence signal and aptamer recognition probes for multiplex detection of water contaminants with high sensitivity and specificity. Finally, several different typical kinds of water contaminants have been successfully detected on our paper disc with limit of detection of 115 cfu/mL for Salmonella , 3 ng/mL for Ochratoxin A and Microcystin-LR , 20 nM for Hg2+ and 4 nM for Pb2+, respectively. Additionally, we designed a compact smartphone-based reading device to enable water quality monitoring at point-of-care. Furthermore, this paper disc-based detection platform can be extended to apply to multiplex detection for disease diagnosis and food safety monitoring. [Display omitted] • A paper disc for multiplex detection of water contaminants with high sensitivity and specificity was developed. • A compact smartphone-based reading device to enable water quality monitoring at point-of-care was developed. • Several typical water contaminants have been successfully detected with satisfying limit of detection. • Simultaneous detection of pathogens, heavy metal ions, and toxins on our paper disc has been demonstrated. [ABSTRACT FROM AUTHOR]

Complex target SELEX always have been an intriguing approach to the scientific community, as it offers the potential discovery of novel biomarkers. We herein successfully performed SELEX on Bungarus caeruleus venom to develop a panel of highly affine aptamers that specifically recognizes the B. caeruleus (common krait) venom and was able to discriminate the B. caeruleus venom from Cobra, Russell's, and Saw-scaled viper's venom. The aptamers generated against the crude venom also lead to the identification of the specific component of the venom, which is β-Bungarotoxin, a toxin uniquely present in the B. caeruleus venom. The best performing aptamer candidates were used as a molecular recognition element in a paper-based device and were able to detect as low as 2 ng krait venom in human serum background. The developed aptamer-based paper device can be used for potential point-of-care venom detection applications due to its simplicity and affordability. [ABSTRACT FROM AUTHOR]

A novel paper working electrode with Pt nanospheres grown in it (Pt-PWE) was first used as a sensor platform and then cancer cells were immobilized on the Pt-PWE (high affinity binding with aptamers). This electrode was first designed to achieve the in situ and real-time determination of H2O2 released from cancer cells to obtain an accurate determination. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) affects between 2 and 14% of pregnant women in the United States every year. Currently, glucose and hemoglobin A1c (HbA1c) are the standard biomarkers used to monitor GDM but HbA1c is representative of 2–3 months of glycemic data and is too infrequent for managing clinical impact of GDM while glucose provides multiple daily readings which arguably are not entirely necessary for mild to moderate GDM and often result in non-compliance from the patient's side. Thus, there is a need for an intermediate biomarker which can be used effectively to monitor the glycemic status of GDM patients. Serum albumin, the most abundant protein in blood, undergoes non-enzymatic glycation in the bloodstream. Owing to its half-life of ~21 days, it can effectively be used as an intermediate biomarker. Normal level of glycation of albumin is between 10 and 16% whereas in diabetic patients it is much higher, between 16 and 40%. Thus, a point-of-care (POC) monitoring system to detect glycated albumin (GA) as a % of total serum albumin has been developed here. Specifically, a dipstick paper fluidic test to measure % glycated albumin has been developed that used an aptamer assay with gold nanoparticles to produce colorimetric measurements. Both the glycated and unglycated versions of albumin were measured in their relevant physiological concentration ranges – 50 μM–300 μM with a limit of detection (LoD) of 6.5 μM for glycated albumin and 500 μM–750 μM with a LoD of 21 μM for unglycated serum albumin. The use of aptamers as recognition elements, instead of commonly used antibodies, not only provided the required sensitivity, specificity, and dynamic range but they also have the added advantage of being stable at room temperature for an extended period of time providing the potential for these dipstick tests to be used for GDM monitoring at the point-of-care (POC). Image 1 • Gestational diabetes requires timely glycemic monitoring, ideally at the point of care. • Glycated albumin can be an ideal intermediate biomarker for gestational diabetes. • Glycated albumin can be measured using colorimetric paper-based assays that cover physiologically relevant ranges. • Aptamers are highly selective for their targets and can be used instead of antibodies. • Aptamer-nanoparticle probes are stable at room temperature in the long term and are ideal for use at the point-of-care. [ABSTRACT FROM AUTHOR]

In this paper, a microfluidic paper-based analytical device is presented for sensitively detecting peptides based on the specific recognition of aptamer and the amplification strategy of hybridization chain reaction (HCR). The aptamer/initiation strand (AP/IS) was designed for the specific target recognition, and the presence of the target peptide could release the initiating sequence from the AP/IS. The released IS could trigger the HCR between two hairpin probes, which could complete the detection for the targets indirectly when the electrochemiluminescence (ECL) probe (Ru(phen)32+) is introduced into the double-strand DNA grooves,which could produce a significantly amplified ECL signal output. Mucin-1 was employed as a model peptide, and the detection limit of the proposed assay is calculated as 8.33 pMwith a range from 25 pM to 50 nM. The novel sensing platform can be widened for the detection of other kinds of peptides as well as potentials used for sensitively detecting other biomolecules, and even cells. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide. Early diagnosis of cancer is crucial for successful treatment which, in turn, will decrease mortality. The development of low-cost, accurate, and easy to operate point-of-need (PON) devices to be used for cancer diagnosis and treatment follow-up is a worldwide need, especially in developing countries. Paper-based analytical devices (PADs) are considered a key solution, as they provide a low-cost platform for developing PON biosensors for cancer biomarker detections. There are various types of 2D and 3D PADs according to the type of paper substrate (filter paper, chromatographic paper, nitrocellulose membranes, etc.), fabrication method (wax printing, screen printing, cutting, etc.), detection technique used (colorimetry, fluorescence, chemiluminescence, electrochemiluminescence, electrochemical, etc.), the assay principle and recognition element used (antibodies, aptamers, DNA, nanoparticles, enzymes, etc.). Controlling all these factors determines the performance, accuracy, and sensitivity of the developed devices. This review discusses all these factors in the different PADs used for detection of cancer biomarkers and summarizes the advantages and disadvantages of each one. [Display omitted] • Paper-based analytical devices for cancer biomarkers detection. • Different types of paper-based analytical devices. • Fabrication methods of paper-based analytical devices. • Different detection techniques for microfluidic paper-based analytical devices. • Applications of microfluidic paper-based analytical devices. [ABSTRACT FROM AUTHOR]

• We have designed a new colorimetric and chemiluminescence paper sensor for sensitive detection of cytochrome C. • β-Co(OH) 2 nanoplates anchored on ordered mesoporous carbon (CMK) were synthesized by electrochemical method. • CMK could be a sufficient catalyzer in chemiluminescence and colorimetric system. • The proposed aptasensor shows a detection limit of 1.0 × 10−9 M and a detection limit of 2.0 × 10−14 M in colorimetric chemiluminescence detection systems, respectively. The detection and measurement of Cytochrome C (Cyt c) has a large impact on the early detection of various types of cancers. So there is a need for developing simple and rapid methods that can be offset by advances in the use of test strips. In this work, a chemiluminescence (CL) and colorimetric aptasensor based method for highly sensitive detection of Cyt c in solution and on paper is introduced. We found that new nano-based material composed of β-Co(OH) 2 nanoplates anchored on ordered mesoporous carbon (CMK) could be a sufficient catalyzer in chemiluminescence and colorimetric systems. In the presence of Cyt c , its specific aptamers would bind to Cyt c and β-Co(OH) 2 CMk can become free thus enhancing the intensity. While in the absence of Cyt c , a weak CL signal was produced, because β-Co(OH) 2 CMK will be surrounded by aptamers. The proposed aptasensor exhibited a wide dynamic range from 5.0 × 10−8–1.0 × 10−3 M (R2 = 0.99) with a detection limit of 1.0 × 10−9 M in colorimetric and 10 × 10−13–5.0 × 10−9 M (R2 = 0.99) and a detection limit of 2.0 × 10−14 M in chemiluminescence detection systems, which was applicable for the determination of Cyt c efficiently. Also, we tested this strategy on paper for both colorimetric and chemiluminescence detection that showed the convenient response according to the obtained results. [ABSTRACT FROM AUTHOR]

Significance: Cardiac troponin I (cTnI) is a primary biomarker for diagnosis of myocardial infarction (MI). In contrast to central laboratory tests for cTnI, point-of-care (POC) testing has the advantage of providing results when the patient is first encountered, which helps high-risk patients to be treated more rapidly and low-risk patients to be released in a timely fashion. A paper fluidic platform is good for POC testing because the paper is abundant, low cost, and disposable. However, current cTnI assays on paper platforms use antibodies as the recognition element, which has limitations due to the high cost of production and antibody stability issues at the POC. Aim: To develop an aptamer-based assay on a paper strip using surface-enhanced resonance Raman spectroscopy (SERRS) for detection of cTnI in the clinically relevant range at the POC. Approach: Gold nanoparticles (AuNPs) were functionalized with a Raman reporter molecule, malachite green isothiocyanate. The functionalized AuNPs were encapsulated in a silica shell and provided a SERRS signal using a handheld Raman system with a 638-nm excitation wavelength. A primary aptamer and a secondary aptamer of cTnI were used in a sandwich assay format to bind the cTnI on a test line of a paper fluidic platform. By measuring the SERRS signal from the test line, the concentration of cTnI was quantitatively determined. Results: The aptamer-based SERRS assay on a paper strip had a detection range of 0.016 to 0.1 ng / ml for cTnI, had good selectivity for cTnI compared to three other markers, had good stability over 10 days, and had good performance in the more complex serum sample matrix. Conclusions: The aptamer-based SERRS assay on a paper strip has the potential to provide a sensitive, selective, stable, repeatable, and cost-effective platform for the detection of cTnI toward eventual use in diagnosis of MI at the POC. [ABSTRACT FROM AUTHOR]

In this note we describe a four-channel paper microfluidic device (μPAD) that utilizes gold nanoparticles (AuNPs) as colorimetric sensors and specifically tailored aptamers to capture a set of targeted drugs, including cocaine, codeine and methamphetamine. The design utilizes salt-induced aggregation of AuNPs to produce a color change that indicates the presence of target analytes. In the absence of the targets, the aptamers bind to AuNPs, preventing aggregation. This μPAD was developed by optimizing the concentrations of aggregating agents, AuNPs and aptamers. The resultant device is sensitive and specific, producing a positive result upon detection of the target analyte. • A four-channel paper microfluidic device with gold nanoparticles and aptamers has been developed for siezed drugs. • The design is optimized for length and width of channels, moving solution, quantity of gold nanoparticles, and aptamers. • The runtime of this μPAD is under 10 min and the LOD is 4 μg for cocaine, codeine and methamphetamine. [ABSTRACT FROM AUTHOR]

Biotoxins are ranges of toxic substances produced by animals, plants, and microorganisms, which could contaminate foods during their production, processing, transportation, or storage, thus leading to foodborne illness, even food terrorism. Therefore, proposing simple, rapid, and effective detection methods for ensuring food free from biotoxin contamination shows a highly realistic demand. Aptamers are single-stranded oligonucleotides obtained from the systematic evolution of ligands by performing exponential enrichment (SELEX). They can specifically bind to wide ranges of targets with high affinity; thus, they have become important recognizing units in safety monitoring in food control and anti-terrorism. In this paper, we reviewed the technical points and difficulties of typical aptamer screening processes for biotoxins. For promoting the understanding of food control in the food supply chain, the latest progresses in rapid optical detection of biotoxins based on aptamers were summarized. In the end, we outlined some challenges and prospects in this field. We hope this paper could stimulate widespread interest in developing advanced sensing systems for ensuring food safety. [ABSTRACT FROM AUTHOR]