Utilizing Heterostructured Porous Particles to Improve Traditional Paper Chromatography for Spontaneous Protein Separation.

Chromatography is a classical technique for protein separation. However, the chromatography column is filled with tightly packed separation materials and requires an additional pressurizing pump to propel the flow of fluidic samples, largely restraining their applications. Here, we combine heterostructured porous particles with paper strips, realizing spontaneous separation of similarly sized proteins. The interconnected nanofibrous structure and good hydrophility of paper strips enable the spontaneous flow of the liquid sample, and the heterostructured porous particles provide versatile tools for protein separation via electrostatic interaction. The fabricated paper strips are inexpensive, user-friendly, and disposable and exhibit good separation performance. This work may offer a new avenue for fabricating on-site bioseparation tools and purifying various biomacromolecules.

Biomineralization-inspired magnetic nanoflowers for sensitive miRNA detection based on exonuclease-assisted target recycling amplification.

Biomineralization-inspired magnetic hybrid nanoflowers were prepared facilely, and capture probes were easily immobilized on the obtained nanoflowers without tedious processing. Based on the magnetic hybrid nanoflowers and exonuclease-assisted target recycling amplification, a fluorescence miRNA sensor was fabricated. The presence of target miRNA leads to the formation of the double-strand structure, which would then be selectively digested by the exonuclease and increase fluorescence intensity. The target miRNA can be released for recycling and signal amplification. Under optimized reaction conditions, the hybrid nanoflower-based miRNA sensor had a broad detection range from 0.001 nM to 100 nM and a limit of detection of 0.23 pM (S/N = 3). The sensitive detection of miRNA in serum was also achieved with recoveries from 94.3% to 116.1%. This work provides a new insight into the fabrication of bioconjugated materials and shows great potential in miRNA sensing.

Dendritic porous silica nanoparticles with high-curvature structures for a dual-mode DNA sensor based on fluorometer and person glucose meter.

A dual-mode DNA sensor was constructed to detect nucleic acid sensitively and selectively. Based on dendritic porous silica nanoparticles (DPSNs) and hybridization chain reaction (HCR) amplification strategy, the fabricated DNA sensor showed good sensitivity with low detection limits down to 2.18 pM and 4.02 pM by fluorescence (excited at 488 nm and emitted at 508 nm) and personal glucose meter (PGM) assays, respectively. This dual-mode detection of DNA offered superior reliability and accuracy and could meet the requirements of different testing environments, including laboratory confirmation and portable detection. Moreover, the impact of nanoparticles morphology on detection performance was also discussed. Due to the center-radial pores, DPSNs had high curvature morphology, which improved the coverage capacity, footprint, and deflection angle of probes. This work fabricated a dual-mode DNA sensor and revealed the relationship between morphology and detection performance, which brought new insights in novel biosensor development.

Heterogeneous Organohydrogel Toward Automated and Interference-Free Gradient Feeding of Drugs in Cell Screening.

Cell-based microarrays are widely used in the fields of drug discovery and toxicology. Precise gradient generation and automated drug feeding are essential for high-throughput screening of live cells in tiny droplets. However, most existing technologies either require sophisticated robotic equipment or cause mechanical/physiological interference with cells. Here, a heterogeneous organohydrogel is presented for automated gradient drug feeding, while ensuring minimal interference with cells. The heterogeneous organohydrogel comprises three crucial components. The bottom surface can automatically generate gradients functioning as a gradient generator, the organohydrogel bulk allows unidirectional transport of drugs without backflow, and the top surface with hydrophilic arrays can firmly anchor the cell-based droplet array to evaluate the concentration-dependent bioeffects of drugs accurately. Such a unique structure enables universal screening of different cell types and drugs dissolved in different solvents, requiring neither additional accessories nor arduous drug functionalization. The heterogeneous organohydrogel with unprecedented automation and non-interference possesses the enormous potential to be a next-generation platform for drug screening.

Smart Janus fabrics for one-way sweat sampling and skin-friendly colorimetric detection.

Functionalized textiles with biofluid management capability have attracted tremendous attention in recent years due to their significant roles in health monitoring and dehydration prevention. Here we propose a one-way colorimetric sweat sampling and sensing system based on a Janus fabric using interfacial modification techniques. The opposite wettability of Janus fabric enables sweat to be quickly moved from the skin surface to the hydrophilic side and colorimetric patches. The unidirectional sweat-wicking performance of Janus fabric not only facilitates adequate sweat sampling but also inhibits the backflow of hydrated colorimetric regent from the assay patch toward the skin, eliminating potential epidermal contaminations. On this basis, visual and portable detection of sweat biomarkers including chloride, pH, and urea is also achieved. The results show that the true concentrations of chloride, pH, and urea in sweat are ∼10 mM, ∼7.2, and ∼10 mM, respectively. The detection limits of chloride and urea are 1.06 mM and 3.05 mM. This work bridges the gap between sweat sampling and a friendly epidermal microenvironment, providing a promising way for multifunctional textiles.

Leaf-Inspired Patterned Organohydrogel Surface for Ultrawide Time-Range Open Biosensing.

Droplet arrays show great significance in biosensing and biodetection because of low sample consumption and easy operation. However, inevitable water evaporation in open environment severely limits their applications in time-consuming reactions. Herein, inspired by the unique water retention features of leaves, it is demonstrated that an open droplet array on patterned organohydrogel surface with water evaporating replenishment (POWER) for ultrawide time-range biosensing, which integrated hydrophilic hydrogel domains and hydrophobic organogel background. The hydrogel domains on the surface can supply water to the pinned droplets through capillary channels formed in the nether organohydrogel bulk. The organogel background can inhibit water evaporation like the wax coating of leaves. Such a unique bioinspired design enables ultrawide time-range biosensing in open environment from a few minutes to more than five hours involving a variety of analytes such as ions, small molecules, and macromolecules. The POWER provides a feasible and open biosensing platform for ultrawide time-range reactions.

Bioinspired liquid-infused surface for biomedical and biosensing applications.

Nature always inspires us to develop advanced materials for diverse applications. The liquid-infused surface (LIS) inspired by Nepenthes pitcher plants has aroused broad interest in fabricating anti-biofouling materials over the past decade. The infused liquid layer on the solid substrate repels immiscible fluids and displays ultralow adhesion to various biomolecules. Due to these fascinating features, bioinspired LIS has been applied in biomedical-related fields. Here, we review the recent progress of LIS in bioengineering, medical devices, and biosensing, and highlight how the infused liquid layer affects the performance of medical materials. The prospects for the future trend of LIS are also presented.

Bioinspired superwettable electrodes towards electrochemical biosensing.

Superwettable materials have attracted much attention due to their fascinating properties and great promise in several fields. Recently, superwettable materials have injected new vitality into electrochemical biosensors. Superwettable electrodes exhibit unique advantages, including large electrochemical active areas, electrochemical dynamics acceleration, and optimized management of mass transfer. In this review, the electrochemical reaction process at electrode/electrolyte interfaces and some fundamental understanding of superwettable materials are discussed. Then progress in different electrodes has been summarized, including superhydrophilic, superhydrophobic, superaerophilic, superaerophobic, and superwettable micropatterned electrodes, electrodes with switchable wettabilities, and electrodes with Janus wettabilities. Moreover, we also discussed the development of superwettable materials for wearable electrochemical sensors. Finally, our perspective for future research is presented.

Patterned Liquid-Infused Nanocoating Integrating a Sensitive Bacterial Sensing Ability to an Antibacterial Surface.

The slippery liquid-infused surfaces show a great antibacterial property. However, most liquid-infused surfaces cannot detect whether or not the unknown aqueous samples contain microorganisms. Therefore, it is highly necessary but a challenge to integrate bacterial sensing capability into antibacterial surface. In this work, we prepared a slippery patterned liquid-infused nanocoating on the glass substrate for integrating bacterial sensing capability into the bacterial repellence surface. Dendritic mesoporous silica nanoparticles (DMSNs) with a suitable particle size of ca. 128 nm were employed as a building block to fabricate the multifunctional nanocoating with a superhydrophilic microwell and hydrophobic periphery by a dip-coating strategy, hydrophobic treatment, photomask-mediated plasma etching, and liquid infusion. Dendritic porous silica nanoparticles (DPSNs) with a larger particle size of ca. 260 nm were uniformly loaded with Au nanoparticles (NPs), providing large surface area for the modification of Raman reporter (4-mercaptobenzoic acid (4-MBA)) and aptamer. Thus, as a Raman tag, the formed DPSNs-Au-MBA-aptamer could achieve sensitive surface-enhanced Raman spectroscopy (SERS) detection of target bacteria. Combined with the Raman tag, the patterned liquid-infused nanocoating not only completely repelled bacteria on the hydrophobic area but also enabled sensitive SERS detection of Staphylococcus aureus in a very low sample volume (1 µL) with a low detection limit of 2.6 colony formation units (CFU)/mL on the antibody-modified superhydrophilic microwell. This research provided a novel and reliable strategy to construct a multifunctional nanocoating with microbial repellence and sensing capabilities.

Space-Confinment-Enhanced Fluorescence Detection of DNA on Hydrogel Particles Array.

Fluorescent biosensors have been widely applied in DNA detection because of their reliability and reproducibility. However, low kinetics in DNA hybridization often brings out long test terms, thus restricting their practical use. Here, we demonstrate unexpected fast DNA fluorescence detection on the confined surface of hydrogel particles. When the pore size and surface charge of hydrogel particles are tailored, DNA molecules can be confined in the outer water layer of hydrogel particles. We fabricated a fluorescence-on DNA sensor based on the hydrogel particle array by utilizing the fluorescence quenching property of graphene oxide and its different adsorption behaviors toward single-strand DNA or double-strand DNA. Benefiting from the confinement effect of hydrogel particle surface and the enrichment effect of water evaporation, the DNA-recognition time was descreased significantly from 3000 s to less than 10 s under the target concentration of 400 nM. Moreover, rapid detection can be achieved at concentrations between 50 and 400 nM. The study provides another insight to fabricate fast biosensors and shows great potential in DNA diagnostics, gene analysis, and liquid biopsy.

Programmable Microparticle Array for In Situ Modification and Multiple miRNA Detection.

Simultaneous detection of multiple miRNAs of one disease can greatly reduce misdiagnosis and improve the detection rate, which is helpful for early cancer diagnosis. Here, a programmable microparticle-array-based acoustic microchip for in situ simultaneous multiple miRNAs detection is developed. On this microchip, the multiple probes-labeled microparticle array can be procedurally arranged in a microfluidic reaction chamber when four orthogonally piezoelectric transducers are applied. The probes-labeled microparticle array offers a platform for full molecular contact under dynamic ultrasonic streaming, and the array supplies a multipoint data correction to reduce the false positive of the detection results for more precisely visible fluorescence multiple target miRNAs sensing. We employed miRNA-21, miRNA-210, and miRNA-155 as specific biomarkers of pancreatic cancer and successfully finished the multiple miRNAs simultaneous detection in the microchip with a detection limit of 139.1, 179.9, and 111.4 pM, respectively. Such a device is programmable by adjusting the imputing frequency and voltage, and target biomarkers can be easily collected when the ultrasound force is released for further analysis, which shows great potential in multiple miRNAs enrichment and simultaneous detection for cancer clinical diagnosis.

Portable detection of Staphylococcus aureus using personal glucose meter based on hybridization chain reaction strategy.

Staphylococcus aureus is one of the most important food-borne bacterial pathogens and causes numerous illnesses. In this work, we report a sensitive and highly selective magnetic-aptamer biosensor based on a personal glucose meter (PGM) platform for the detection of Staphylococcus aureus. The aptamer for Staphylococcus aureus was immobilized on the magnetic bead by hybridization with the capture probe P. In the presence of Staphylococcus aureus, the aptamer was dissociated from the magnetic bead. Then the capture probe was exposed and could be hybridized with a biotinylated probe to trigger the DNA hybridization chain reaction (HCR), thus achieving the signal amplification. The concentration of streptavidin-labeled invertase can be read by PGM, thus can lead to the portable quantitative detection of Staphylococcus aureus. After optimization of various conditions, 5 µM probe P, the MB-P reaction time for 36 h, the competition time for 60 min, 0.5 µM H1 & H2, 0.5 M sucrose and the sucrose invertase catalytic reaction time for 50 min was chosen to achieve the better sensor performance. Under the optimal conditions, the fabricated sensor offers high sensitivity with the limit of detection about 2 CFU/mL. This sensitive PGM based sensor could successfully evaluate the Staphylococcus aureus concentration in real food samples, and the results are consistent with those obtained by using plate counting methods. Moreover, the PGM sensor can greatly reduce the required time compared to the plate counting methods. The fabricated sensor supplies an ideal solution for rapid portable detection of bacterial pathogens and holds its potential use in the quality control for agriculture and food enterprises, entry-exit inspection and quality testing for food.

Bioinspired wettable-nonwettable micropatterns for emerging applications.

Superhydrophilic and superhydrophobic surfaces are prevalent in nature and have received tremendous attention due to their importance in both fundamental research and practical applications. With the high interdisciplinary research and great development of microfabrication techniques, artificial wettable-nonwettable micropatterns inspired by the water-collection behavior of desert beetles have been successfully fabricated. A combination of the two extreme states of superhydrophilicity and superhydrophobicity on the same surface precisely, wettable-nonwettable micropatterns possess unique functionalities, such as controllable superwetting, anisotropic wetting, oriented adhesion, and other properties. In this review, we briefly describe the methods for fabricating wettable-nonwettable patterns, including self-assembly, electrodeposition, inkjet printing, and photolithography. We also highlight some of the emerging applications such as water collection, controllable bioadhesion, cell arrays, microreactors, printing techniques, and biosensors combined with various detection methods. Finally, the current challenges and prospects of this renascent and rapidly developing field are proposed and discussed.

A three-dimensional DNA walking machine for the ultrasensitive dual-modal detection of miRNA using a fluorometer and personal glucose meter.

Three-dimensional (3D) DNA walking machines inspired by natural molecular machines have attracted significant attention due to their high walking efficiency and signal amplification capability. Herein, we report a 3D DNA walking machine for the dual-modal detection of miRNA using a fluorometer and personal glucose meter (PGM). The 3D DNA walking machine on magnetic beads (MBs) was coated with the BHQ-H1-FAM hairpin structures (DNA tracks), activated by target miRNA-21 (walking strand) and propelled by a strand displacement reaction. During these processes, the fluorescence of FAM on H1 was turned on (first signal), and the invertase on H2 was introduced into the surface of the MBs. After being separated by an external magnetic field, the invertase hydrolyzed sucrose into glucose to generate a second signal, which was quantified by the PGM. The developed 3D DNA walking machine showed high sensitivity and good specificity, and the detection limits of 98 pM and 60 pM were obtained for the fluorescence-based assay and PGM-based assay, respectively. Compared with the single-modal detection, the developed DNA walking machine can achieve a unique double signal readout and more reliable sensitive performance. In addition, the proposed 3D DNA walking machine was successfully applied to detect miRNA in real biological samples. The 3D DNA walking machine with dual-modal detection has potential applications in disease diagnostics and clinical applications and can satisfy different testing requirements both in the laboratory and field.

Bioinspired DNA-Inorganic Hybrid Nanoflowers Combined with a Personal Glucose Meter for Onsite Detection of miRNA.

Biomineralization is an important process in nature, by which living organisms participate in producing organic/inorganic hybrid materials and the resultant materials show sophisticated structures and excellent physical and chemical properties. Inspired by biomineralization, DNA-Cu3(PO4)2 hybrid nanoflowers (HNFs) were prepared, which exhibited high stability, a high surface-to-volume ratio, and good DNA encapsulation ability. A facile thread platform for microRNA (miRNA) detection was fabricated by employing DNA-Cu3(PO4)2 HNFs as captors, and the signal could be easily read out by a personal glucose meter. The fabricated biosensor could detect miRNA-21 quantitatively and a detection limit of 0.41 nM was achieved. Furthermore, miRNA in A549 cell lysate could also be detected without pretreatment. In this work, we achieved a fast, simple, low-cost method based on the bioinspired DNA-inorganic HNFs for the specific and sensitive detection of miRNA in both aqueous solution and biological samples, indicating its great promise in biomedical and clinical applications.