Portable dual-mode paper chips for highly sensitive and rapid determination of aflatoxin B1 via an aptamer-gated MOFs.

Paper chip as a representative microfluidic device has been mushroomed for rapid identification of contaminants in agro-food. However, the sensitivity and accuracy have still been challenged by inevitable background noise or interference in food matrix. Herein, we designed and fabricated a dual-mode paper chip (DPC) by assembling a patterned paper electrode with a platinum nanoparticles-treated colorimetric region through a flow channel. Dual-mode outputs were guided by an aptamer-gated UiO-66-NH2 metal-organic frameworks (MOFs). UiO-66-NH2 loaded with 3, 3', 5, 5'-tetramethylbenzidine (TMB) was controlled by a switch comprised of CdS quantum dots-aptamer. Aflatoxin B1 (AFB1, a kind of carcinogenic mycotoxin) target came and induced TMB release, triggering colorimetric and ECL signals on DPC, ultra-high sensitivity with a detection limit of 7.8 fg/mL was realized. The practicability of the DPC was also confirmed by spiking AFB1 in real corn samples. This portable paper-based device provides an ideal rapid detection platform tailored for diverse food contaminants analysis.

Fabrication and optimization of paper chips from calcinated Fe-MOFs for rapid and in situ visual detection of tetracyclines in water environments.

Antibiotics such as tetracyclines (TCs) have become a major threat to ecosystem safety and human health, as their abuse has caused the occurrence and proliferation of antibiotic-resistant bacteria and genes. Currently, there is still a lack of convenient in situ methods for the detection and monitoring of TC pollution in actual water systems. This research reports a paper chip based on the complexation of iron-based metal organic frameworks (Fe-MOFs) and TCs for rapid and in situ visual detection of representative oxytetracycline (OTC) pollution in water environments. The optimized complexation sample NH2-MIL-101(Fe)- 350 obtained by calcination at 350 °C exhibited the highest catalytic activity and was then used for paper chip fabrication by printing and surface modification. Notably, the paper chip demonstrated a detection limit as low as 17.11 nmol L-1 and good practicability in reclaimed water, aquaculture wastewater, and surface water systems, with OTC recovery rates of 90.6-111.4%. More importantly, the presence of dissolved oxygen (9.13-12.7 mg L-1), chemical oxygen demand (0.52-12.1 mg L-1), humic acid (< 10 mg L-1), Ca2+, Cl-, and HPO42- (< 0.5 mol L-1) had negligible interference on the detection of TCs by the paper chip. Therefore, this work has developed a promising method for rapid and in situ visual monitoring of TC pollution in actual water environments.

Paper-Based Radial Flow Assay Integrated to Portable Isothermal Amplification Chip Platform for Colorimetric Detection of Target DNA.

A novel integrated detection system that introduces a paper-chip-based molecular detection strategy into a polydimethylsiloxane (PDMS) microchip and temperature control system was developed for on-site colorimetric detection of DNA. For the paper chip-based detection strategy, a padlock probe DNA (PLP)-mediated rolling circle amplification (RCA) reaction for signal amplification and a radial flow assay according to the Au-probe labeling strategy for visualization were optimized and applied for DNA detection. In the PDMS chip, the reactions for ligation of target-dependent PLP, RCA, and labeling were performed one-step under isothermal temperature in a single chamber, and one drop of the final reaction solution was loaded onto the paper chip to form a radial colorimetric signal. To create an optimal analysis environment, not only the optimization of molecular reactions for DNA detection but also the chamber shape of the PDMS chip and temperature control system were successfully verified. Our results indicate that a detection limit of 14.7 nM of DNA was achieved, and non-specific DNAs with a single-base mismatch at the target DNA were selectively discriminated. This integrated detection system can be applied not only for single nucleotide polymorphism identification, but also for pathogen gene detection. The adoption of inexpensive paper and PDMS chips allows the fabrication of cost-effective detection systems. Moreover, it is very suitable for operation in various resource-limited locations by adopting a highly portable and user-friendly detection method that minimizes the use of large and expensive equipment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13206-023-00101-7.

Auto-fluorescence of cellulose paper with spatial solid phrase dispersion-induced fluorescence enhancement behavior for three heavy metal ions detection.

Auto-fluorescence of cellulose paper is often considered as an interfering fluorescence, which directly impedes the cellulose paper as a substrate material. This paper creatively explored the composition and properties of auto-fluorescence, and lignosulfonate was primarily speculated as the main source of auto-fluorescence. Surprisingly, its spatial solid phrase dispersion-induced fluorescence enhancement behavior was found. Then, cellulose paper was modified with Mn-doped ZnS quantum dots, and the prepared ratiometric fluorescent paper chip has good performances on morphology, stability, and fluorescence properties. Besides, the paper chip exhibited different fluorescence responses to three heavy metal ions in water sample. The limit of detection for Cd2+, Hg2+ and Pb2+ reached 1.61 nM, 0.01 nM, and 0.02 nM, respectively. In short, the molecular simulation results theoretically proved that heavy metal ions owned substitution affinity with lignosulfonate. Ultimately, this study was the first attempt to utilize paper-based auto-fluorescence, which could better accelerate the development of paper-based chips.

Ratiometric Monitoring of Biogenic Amines by a Simple Ammonia-Response Aiegen.

Herein, we developed a paper-based smart sensing chip for the real-time, visual, and non-destructive monitoring of food freshness using a ratiometric aggregation-induced emission (AIE) luminogen (i.e., H+MQ, protonated 4-(triphenylamine)styryl)quinoxalin-2(1H)-one) as pH sensitive indicators. Upon exposure to amine vapors, the deprotonation of H+MQ occurs and triggers its color change from blue to yellow, with the fluorescence redshift from blue to amaranth. Consequently, we successfully achieved the sensitive detection of ammonia vapors by recording the bimodal color and fluorescence changes. Given the high sensitivity of H+MQ to ammonia vapor, a paper-based smart sensor chip was prepared by depositing H+MQ on the commercial qualitative filter paper through a physical deposition strategy. After being placed inside the sealed containers, the developed H+MQ-loaded paper chip was applied to the real-time monitoring of biogenic amine contents according to its color difference and ratio fluorescence change. The detection results were further compared with those obtained by the high-performance liquid chromatography method, which verified the feasibility of the designed paper chip for the food spoilage degree evaluation. Briefly, this work indicates that the designed H+MQ-loaded paper chip could be a promising approach for improving food freshness monitoring.

Microfluidic paper-based chip for parathion-methyl detection based on a double catalytic amplification strategy.

The rapid detection of insecticides such as parathion-methyl (PM) requires methods with high sensitivities and selectivities. Herein, a dual catalytic amplification strategy was developed using Fe3O4 nanozyme-supported carbon quantum dots and silver terephthalate metal-organic frameworks (Fe3O4/C-dots@Ag-MOFs) as current amplification elements. Based on this strategy, a novel electrochemical microfluidic paper-based chip was designed to detect PM. Fe3O4/C-dots@Ag-MOFs were synthesised by a hydrothermal method, and a molecularly imprinted polymer (MIP) was then synthesised on the surface of Fe3O4/C-dots@Ag-MOFs using PM as a template molecule. Finally, the reaction zone of a chip was modified with MIP/Fe3O4/C-dots@Ag-MOFs. PM from a sample introduced into the reaction zone was captured by the MIP, which generated a reduction current response at - 0.53 V in a three-electrode system embedded in the chip. Simultaneous catalysis by Fe3O4/C-dots and Ag-MOFs significantly enhanced the signal. The chip had a detection limit of 1.16 × 10-11 mol L-1 and was successfully applied to the determination of PM in agricultural products and environmental samples with recovery rates ranging from 82.7 to 109%, with a relative standard deviation (RSD) of less than 5.0%. This approach of combining a dual catalytic amplification strategy with an MIP significantly increased the sensitivity as well as selectivity of chips and can potentially be used to detect a wide variety of target analytes using microfluidic paper-based chips.

Rapid Detection of Dimethoate in Soybean Samples by Microfluidic Paper Chips Based on Oil-Soluble CdSe Quantum Dots.

Given the imperative of monitoring organophosphorus pesticides (OPs) residues in the ecosystem, here a novel, facile and sensitive fluorescence sensor is presented for the rapid detection of dimethoate. In this work, surface molecularly imprinted polymer (SMIP) and microfluidic technology had been introduced to enhance the selectivity and portability of the described methodology. Oil-soluble CdSe quantum dots (QDs) synthesized in a green way were used as fluorescent material for the selective detection of dimethoate on the basis of static quenching and photoinduced electron transfer mechanism. Among many kinds of paper materials, glass fiber paper was used as the novel substrate of paper chip due to low pristine fluorescence and better performance when combining CdSe QDs. In the process of molecular imprinting, the interaction between several functional monomers and dimethoate molecule was investigated and simulated theoretically by software to improve the selectivity of the sensor. Consequently, the fabricated novel detection platform could effectively respond to dimethoate in 10 min with the concentration range of 0.45-80 µmol/L and detection limit of 0.13 µmol/L. The recovery in the spiked experiment soybean sample was in an acceptable range (97.6-104.1%) and the accuracy was verified by gas chromatography-mass spectrometry, which signified the feasibility and potential in food sampling.

Microfluidic colorimetric detection platform with sliding hybrid PMMA/paper microchip for human urine and blood sample analysis.

A microfluidic colorimetric detection (MCD) platform consisting of a sliding hybrid PMMA/paper microchip and a smart analysis system is proposed for the convenient, low-cost and rapid analysis of human urine and whole blood samples. The sliding PMMA/paper microchip comprises a PMMA microfluidic chip for sample injection and transportation, a paper strip for sample filtration (urine) or separation (blood), and a sealed paper-chip detection zone for sample reaction and detection. In the proposed device, the paper-chip is coated with bicinchoninic acid (BCA) and biuret reagent and is then assembled into the PMMA microchip and packaged in aluminum housing. In the detection process, the PMMA/paper microchip is slid partially out of the housing, and 2 µL of sample (urine or whole blood) is dripped onto the sample injection zone. The chip is then slid back into the housing and the sample is filtered/separated by the paper strip and transferred under the effects of capillary action to the sealed paper-chip detection zone. The housing is inserted into the color analysis system and heated at 45 °C for 5 min to produce a purple-colored reaction complex. The complex is imaged using a CCD camera and the RGB color intensity of the image is then analyzed using a smartphone to determine the total protein (TP) concentration of the sample. The effectiveness of the proposed method is demonstrated using TP control samples with known concentrations in the range of 0.03-5.0 g/dL. The detection results obtained for 50 human urine samples obtained from random volunteers are shown to be consistent with those obtained from a conventional hospital analysis system (R2 = 0.992). Moreover, the detection results obtained for the albumin (ALB) and creatine (CRE) concentrations of 50 whole blood samples are also shown to be in good agreement with the results obtained from the hospital analysis system (R2 = 0.982 and 0.988, respectively).

Multichannel Paper Chip-Based Gas Pressure Bioassay for Simultaneous Detection of Multiple MicroRNAs.

Simultaneous detection of multi-biomarkers not only enhances the accuracy of disease diagnosis but also improves detection efficiency and reduces cost. It is vital to achieve portable, simple, low-cost, and simultaneous detection of biomarkers for point-of-care (POC) diagnostics in a low-resource setting. Herein, a multichannel paper chip-based gas pressure bioassay was developed for the simultaneous detection of multiple biomarkers by combining multichannel paper chips with a portable gas pressure meter. Four DNA tetrahedral probes (DTPs) were used as capture probes and were immobilized in different detection zones of the paper chips to improve hybridization efficiency and reduce nonspecific adsorption. The formation of a sandwich structure between target microRNAs (miRNAs), the capture probe, and platinum nanoparticles (PtNPs)-modified complementary DNA (PtNPs-cDNA) transformed biomolecular recognition into quantitative detection of gas pressure. Four lung cancer-related miRNAs were detected simultaneously by a portable gas pressure meter. There is a good linear relationship between gas pressure and the logarithm of miRNA concentration in the range of 10 pM to 100 nM. Compared with single-stranded DNA capture probe, the signal-to-noise (S/N) of DNA tetrahedral probes improved more than 3 times. Using ring-oven washing, the unbound reagents in all channels of the paper chip were simultaneously and continuously washed away, leading to a more cheap, simple, and fast separation than magnetic separation. Therefore, it offers a promising multichannel paper chip-based gas pressure bioassay for portable and simultaneous detection of multiple biomarkers.

Bladder cancer hunting: A microfluidic paper-based analytical device.

Bladder cancer is the fourth most common cancer in men, and it is becoming a prevalent malignancy. Most of the regular clinical examinations are prompt evaluations with cystoscopy, renal function testing, which require high-precision instrument, well-trained operators, and high cost. In this study, a microfluidic paper-based analytical device (µPAD) was fabricated to detect nuclear matrix protein 22 (NMP22) and bladder cancer antigen (BTA) from the urine samples. Urine samples were collected from 11 bladder cancer patients and 10 well-beings as experiment and control groups, respectively, to verify the working efficiency of µPAD. A remarkable checkout efficiency of up to 90.91% was found from the results. Meanwhile, this method is feasible for home-based self-detection from urine samples within 10 min for the total process, which provides a new way for quick, economical, and convenient tumor diagnosis, prognosis evaluation, and drug response.

Aptamer-Conjugated Polydiacetylene Colorimetric Paper Chip for the Detection of Bacillus thuringiensis Spores.

A colorimetric polydiacetylene (PDA) paper strip sensor that can specifically recognize Bacillus thuringiensis (BT) HD-73 spores is described in this work. The target-specific aptamer was combined with PDA, and the aptamer-conjugated PDA vesicles were then coated on polyvinylidene fluoride (PVDF) paper strips by a simple solvent evaporation method. The PDA-aptamer paper strips can be used to detect the target without any pre-treatment. Using the paper strip, the presence of BT spores is directly observable by the naked eye based on the unique blue-to-red color transition of the PDA. Quantitative studies using the paper strip were also carried out by analyzing the color transitions of the PDA. The specificity of this PDA sensor was verified with a high concentration of Escherichia coli, and no discernable change was observed. The observable color change in the paper strip occurs in less than 1 h, and the limit of detection is 3 × 107 CFU/mL, much below the level harmful to humans. The PDA-based paper sensor, developed in this work, does not require a separate power or detection device, making the sensor strip highly transportable and suitable for spore analysis anytime and anywhere. Moreover, this paper sensor platform is easily fabricated, can be adapted to other targets, is highly portable, and is highly specific for the detection of BT spores.

A visual Hg2+ detection strategy based on distance as readout by G-quadruplex DNAzyme on microfluidic paper.

In this work, we have developed a simple, fast and visual Hg2+ detection strategy based on distance as readout on paper chip by the Hg2+-mediated formation of G-quadruplex-hemin DNAzymes. In the presence of Hg2+, the two oligonucleotides hybridize to form G-quadruplex DNA by T-Hg2+-T base pair, which was able to bind hemin to form the catalytically active G-quadruplex-hemin DNAzymes. Once DNAzymes were added to react with the precipitated 3,3,5,5-tetramethyl benzidine (TMB) immobilized on the sample area, a visible color band was produced, and the formed length was positively correlated with the concentration of Hg2+. This biosensor is capable of selectively detecting mercuric ions with good reproducibility and satisfactory dynamic range. The limit of detection was low to 0.23 nM. Therefore, this strategy not only provides a visual and quick screen of Hg2+, but also shows a promising future in monitoring analysis of other metal ions in POC diagnostic field.

Self-Powered and Green Ionic-Type Thermoelectric Paper Chips for Early Fire Alarming.

Early fire alarming is of vital importance to lower the damages led by forest fires. Thus far, methods to monitor the forest fires at their early stage are mainly focused on artificial ground patrol, unmanned aerial vehicle cruise monitoring, observation by watchtower, or satellite inspection, whereas these methods are practically encountered with the problems of untimely feedback before the forest fires are out of control. This work proposes a particular kind of self-powered, low-cost, and green thermoelectric paper chips based on the principle of self-assembly and disassembly of ionic liquids on the surface of gold electrodes. By adjustment of the species of ionic liquids, both "n- and p-type" thermoelectric behaviors have been exploited that correspond to the opposite open-circuit voltages. Owing to the fluidic nature of ionic liquids, those "n- and p-type" thermoelectric units can be readily connected in series on one paper chip, leading to remarkable voltage signals in the presence of the temperature difference of 35 K. Followed by signal acquisition and transmission, such a thermoelectric paper chip successfully affords immediate electrical alarming at the early stage of an afire circumstance.

An innovative paper-based device for DNA extraction from processed meat products.

Detection of food adulteration is a challenge. However, the identification of adulterated meat in processed products is important for health and personal preference. Mitochondrial genomic DNA (mtDNA) is a good candidate for reliable identification of meat ingredients; however, the extraction of mtDNA from processed products is a bottleneck for development of detection strategies. Therefore, we constructed a rapid (~5 min) mtDNA extraction device. mtDNAs from different meat samples, such as pork (Sus scrofa), chicken (Gallus gallus), and beef (Bos taurus), were successfully detected in up to 0.1% adulterated animal species. We believe that the proposed strategy could be applied to detect animal species from processed meat products to reduce fraudulent practices.

A PET/paper chip platform for high resolution sulphur dioxide detection in foods.

A convenient assay platform comprising a PET/paper chip (PP-chip) and a smart analytical device is developed for detection of sulphur dioxide (SO2) concentration. In the presented approach, the distilled SO2 solution is dropped onto the detection region of the PP-chip and undergoes a reaction with an acid-based reagent. The resulting color variation is analyzed through a high-resolution camera (CMOS) and the reacted image is processed by a RGB (red, green and blue) analytical app installed on a smartphone. Results show that the known SO2 concentrations ranging from 10 to 300 ppm indicate that the high linear relationship (R2 = 0.9981) between the (R (red) + G (green) - B (blue)) value and SO2 concentration. Moreover, a high measurement resolution is equal to 1.45 ppm/a.u. The presented assay platform was proved to detect the SO2 concentrations of twenty-five practical food samples. Compared with the developed assay platform and certified inspection technique, the deviation of SO2 measurement does not exceed 3.82%. It was satisfactory to apply this developed assay platform to analyze the SO2 concentration in the practical samples.

Handheld Inkjet Printing Paper Chip Based Smart Tetracycline Detector.

Tetracycline is widely used as medicine for disease treatments and additives in animal feeding. Unfortunately, the abuse of tetracycline inevitably causes tetracycline residue in animal-origin foods. Though classical methods can detect tetracycline in high sensitivity and precision, they often rely on huge and expensive setups as well as complicated and time-consuming operations, limiting their applications in rapid and on-site detection. Here, we propose a handheld inkjet printing paper chip based smart tetracycline detector: tetracycline can be determined by inkjet printing prepared paper chip based enzyme-linked immunosorbent assay (ELISA) with the advantages of high sensitivity, excellent specificity and low cost; moreover, a smartphone based paper chip reader and application is designed for automatically determining tetracycline with simple operations, high precision and fast speed. The smart tetracycline detector with a compact size of 154 mm × 80 mm × 50 mm and self-supplied internal power can reach a rather low detection limit of ~0.05 ng/mL, as proved by practical measurements. It is believed the proposed handheld inkjet printing paper chip based smart tetracycline detector is a potential tool in antibiotic sensing for routine uses at home and on-site detection in the field.

Simple Screening of Listeria monocytogenes Based on a Fluorescence Assay via a Laminated Lab-On-Paper Chip.

Monitoring food safety is essential for protecting the health and safety of consumers. Conventional methods used are time consuming and laborious, requiring anywhere from three to seven days to obtain results. Thus, better monitoring methods are required. In this study, a laminated lab-on-paper chip was developed, and its use for the screening of ready-to-eat seafood was demonstrated. The assay on a chip was based on loop-mediated isothermal DNA amplification (LAMP) of the hly gene of Listeria monocytogenes and fluorescence signal detection via SYBR GoldTM. Overall assay processes were completed in 4.5 h., (including 3.5 h. incubation for the bacteria enrichment, direct DNA amplification with no DNA extraction, and signal detection), without relying on standard laboratory facilities. Only positive samples induced fluorescence signals on chip upon illumination with UV light (λ = 460). The method has a limit of detection of 100 copies of L. monocytogenes DNA per 50 g of sample. No cross-reactivity was observed in samples contaminated with other bacteria. On-site monitoring of the seafood products using this chip revealed that one of 30 products from low sanitation vendors (3.33%) were contaminated, and these agreed with the results of PCR. The results demonstrated a benefit of this chip assay for practical on-site monitoring.

Combining field-amplified sample stacking with moving reaction boundary electrophoresis on a paper chip for the preconcentration and separation of metal ions.

A common drawback of paper-based separation devices is their poor detection limit. In this study, we combined field-amplified sample stacking with moving reaction boundary electrophoresis on a paper chip with six array channels for the parallel separation and concentration of multiple samples. With a new hyphenated technique, the brown I2 from the Fe3+ /I- oxidation-reduction reaction emerged near the boundary between the dilute ethylene diamine tetraacetic acid and potassium iodide and highly concentrated KCl solutions. For the separation and concentration of three components, Cr3+ , Cu2+ , and Fe3+ , the Fe3+ detection limit was improved at least 266-fold by comparing the hyphenated technique with moving reaction boundary electrophoresis. The detection limit of Fe3+ was found to be as low as 0.34 ng (20 µM) on the paper chip. We also demonstrated the analysis of a real sample of four metal ions, with detection limits as follows: 0.16 µg Cr3+ , 1.5 µg Ni2+ , 0.64 µg Cu2+ , and 1.5 µg Co2+ . The synergy of field-amplified sample stacking and moving reaction boundary electrophoresis in the micron paper-based array channels dramatically improved the detection limit and throughput of paper-based electrophoresis.

Active digital microfluidic paper chips with inkjet-printed patterned electrodes.

Active, paper-based, microfluidic chips driven by electrowetting are fabricated and demonstrated for reagent transport and mixing. Instead of using the passive capillary force on the pulp to actuate a flow of a liquid, a group of digital drops are transported along programmed trajectories above the electrodes printed on low-cost paper, which should allow point-of-care production and diagnostic activities in the future.

Visible paper chip immunoassay for rapid determination of bacteria in water distribution system.

Paper chips for immunoassay were patterned by screen printing of polydimethylsiloxane (PDMS) or wax pencil drawing. The methods for paper chip patterning are cheap, convenient, rapid and suitable for most laboratories. The whole time for patterning a paper chip is no more than 10 min. Visible immunoassay for the detection of bacteria (Escherichia coli ) has been realized using the paper chip, on which the antibody for capturing E. Coli was immobilized on the detection zones of the paper chip, while the detection antibody was labeled with gold nanoparticles (AuNPs) as a signal reporter. After an immunological reaction, the AuNPs bound on the paper chip can effectively catalyse the reduction of silver ions during the silver enhancing step, generating a visible result that can be read by naked eyes. The quantitative results can be acquired by scanning the silver stained paper chip with a commercial scanner/or digital camera. The density of E. coli in water samples can be measured after calibrating the gray value of silver stained spots with the logarithmic number of bacteria. The time and reagents consumed on the paper chip immunoassay is much smaller than those of conventional ELISA, while the sensitivity of the paper chip immunoassay is comparable to conventional ELISA. The technology proposed in this work displays a great potential in the in-situ analysis when daily monitoring of water quality are required.