Ultrasound-Induced Enrichment of Ultra-Trace miRNA Biosensing in Nanoliter Samples.

The rapid and accurate analysis of micro-samples is a crucial foundation for precision medicine, particularly for early screening and monitoring of cancer, where it holds significant importance. Ultrasound-based multifunctional biocompatible manipulation techniques have been extensively applied in a variety of biomedical fields, providing insights for the development of rapid, cost-effective, and accurate biomarker detection strategies. In this chapter, we combine ultrasound-based gradient pressure fields with functionalized microsphere enrichment to develop a biosensing method for ultra-trace miRNA enrichment in nanoliter samples without PCR. This system relies on inexpensive capillaries, enabling simultaneous visual imaging and trace sample detection.

Wearable Vertical Graphene-Based Microneedle Biosensor for Real-Time Ketogenic Diet Management.

Ketogenic diets have attracted substantial interest in the treatment of chronic diseases, but there are health risks with long-term regimes. Despite the advancements in diagnostic and therapeutic methods in modern medicine, there is a huge gap in personalized health management of this dietary strategy. Hence, we present a wearable microneedle biosensor for real-time ketone and glucose monitoring. The microneedle array possesses excellent mechanical properties, allowing for consistent sampling of interstitial biomarkers while reducing the pain associated with skin puncture. Vertical graphene with outstanding electrical conductivity provides the resulting sensor with a high sensitivity of 234.18 µA mM-1 cm-2 and a low limit detection of 1.21 µM. When this fully integrated biosensor was used in human volunteers, it displayed an attractive analytical capability for tracking the dynamic metabolite levels. Moreover, the results of the on-body evaluation established a significant correlation with commercial blood measurements. Overall, this cost-effective and efficient sensing platform can accelerate the application of a ketogenic diet in personal nutrition and wellness management.

Colorimetric detection of electrolyte ions in blood based on biphasic microdroplet extraction.

BACKGROUND: Timely diagnosis and prevention of diseases require rapid and sensitive detection of biomarkers from blood samples without external interference. Abnormal electrolyte ion levels in the blood are closely linked to various physiological disorders, including hypertension. Therefore, accurate, interference-free, and precise measurement of electrolyte ion concentrations in the blood is particularly important. RESULTS: In this work, a colorimetric sensor based on a biphasic microdroplet extraction is proposed for the detection of electrolyte ions in the blood. This sensor employs mini-pillar arrays to facilitate contact between adjacent blood microdroplets and organic microdroplets serving as sensing phases, with any color changes being monitored through a smartphone's colorimetric software. The sensor is highly resistant to interference and does not require pre-treatment of the blood samples. Remarkably, the sensor exhibits exceptional reliability and stability, allowing for rapid enrichment and detection of K+, Na+, and Cl- in the blood within 10 s (Cl-), 15 s (K+) and 40 s (Na+) respectively. SIGNIFICANCE: The colorimetric sensor based on biphasic microdroplet extraction offers portability due to its compact size and ease of operation without the need for large instruments. Additionally, it is location-independent, making it a promising tool for real-time biomarker detection in body fluids such as blood.

Smart Janus textiles for biofluid management in wearable applications.

Janus textiles with asymmetric wettability have shown great potential in wearable applications due to their ability to manage biofluids efficiently. This review summarizes recent advances in smart Janus textiles for biofluid control and monitoring, focusing on wearable technologies. We first introduce the design configurations and fabrication approaches of Janus textiles, including asymmetric generation and asymmetric decoration strategies. We then highlight their diverse wearable applications spanning personal thermal management textiles, sweat sensors, hemostatic wound dressings, and protective equipment. These textiles offer innovative solutions for directional sweat transport, enhancing cooling and humidity control, and providing antibacterial properties. Finally, we discuss current limitations in durability, biocompatibility, and manufacturing scalability, alongside emerging opportunities in the field of smart Janus textiles.

Multiscale Heterogeneities-Based Piezoresistive Interfaces with Ultralow Detection Limitation and Adaptively Switchable Pressure Detectability.

Mechanical compliance and electrical enhancement are crucial for pressure sensors to promote performances when perceiving external stimuli. Here we propose a bioinspired multiscale heterogeneity-based interface to adaptively regulate its structure layout and switch to desirable piezoresistive behaviors with ultralow detection limitation. In such a multiscale heterogeneities system, the micro-/nanoscale spiny Ag-MnO2 heterostructure contributes to an ultralow detection limitation of 0.008 Pa and can perceive minor pressure increments under preloads with high resolution (0.0083%). The macroscale heterogeneous orientation of the cellular backbone enables anisotropic deformation, allowing the sensor to switch to rational sensitivity and working range (e.g., 580 kPa-1 for 0-20 kPa/54 kPa-1 for 60-140 kPa) as required. The sensor's stepwise activation progresses from the micro-/nanoscale heterostructure to the macroscale heterogeneous orientation, which can adaptively match diverse sensing tasks in complex applications scenarios. This multiscale heterogeneous and switchable design holds immense potential in the development of intelligent electromechanical devices, including wearable sensors, soft robotics, and smart actuators.

Integrated phase separation in microliter droplets for ultratrace-enriching biomarker analysis.

Ultratrace-enriching biomarker analysis is an effective method for achieving highly accurate and enhanced sensitive detection. In this study, we have developed an enrichment detection platform by combining a minipillar array with an aqueous two-phase system (ATPS) for ultratrace enriching biomarker analysis. After optimizing the enrichment conditions of ATPS, target miRNAs at ultratrace levels specifically accumulate in the DEX-rich phase, which significantly increases the target miRNA concentration-related fluorescence intensity. Compared to non-enriched miRNA in the single-phase PEG solution, the detection limit of ATPS-enriched miRNA had improved more than 200-fold. The ATPS-based enrichment detection strategy offers a novel and convenient approach for the simultaneous detection of biomarkers with ultratrace.

Design and application of dual-emission metal-organic framework-based ratiometric fluorescence sensors.

Metal-organic frameworks (MOFs) are novel inorganic-organic hybridized crystals with a wide range of applications. In the last twenty years, fluorescence sensing based on MOFs has attracted much attention. MOFs can exhibit luminescence from metal nodes, ligands or introduced guests, which provides an excellent fluorescence response in sensing. However, single-signal emitting MOFs are susceptible to interference from concentration, environment, and excitation intensity, resulting in poor accuracy. To overcome the shortcomings, dual-emission MOF-based ratiometric fluorescence sensors have been proposed and rapidly developed. In this review, we first introduce the luminescence mechanisms, synthetic methods, and detection mechanisms of dual-emission MOFs, highlight the strategies for constructing ratiometric fluorescence sensors based on dual-emission MOFs, and classify them into three categories: intrinsic dual-emission and single-emission MOFs with luminescent guests, and non-emission MOFs with other luminescent materials. Then, we summarize the recent advances in dual-emission MOF-based ratiometric fluorescence sensors in various analytical industries. Finally, we discuss the current challenges and prospects for the future development of these sensors.

Two-Dimensional Nickel Porphyrinic Metal-Organic Framework-Modified Electrode for Electrochemical Sensing.

Due to their highly exposed active sites and high aspect ratio caused by their substantial lateral dimension and thin thickness, two-dimensional (2D) metal-organic framework (MOF) nanosheets are currently considered a potential hybrid material for electrochemical sensing. Herein, we present a nickel-based porphyrinic MOF nanosheet as a versatile and robust platform with an enhanced electrochemical detection performance. It is important to note that the nickel porphyrin ligand reacted with Cu(NO3)2·3H2O in a solvothermal process, with polyvinylpyrrolidone (PVP) acting as the surfactant to control the anisotropic development of creating a 2D Cu-TCPP(Ni) MOF nanosheet structure. To realize the exceptional selectivity, sensitivity, and stability of the synthesized 2D Cu-TCPP(Ni) MOF nanosheet, a laser-induced graphene electrode was modified with the MOF nanosheet and employed as a sensor for the detection of p-nitrophenol (p-NP). With a detection range of 0.5-200 µM for differential pulse voltammetry (DPV) and 0.9-300 µM for cyclic voltammetry (CV), the proposed sensor demonstrated enhanced electrochemical performance, with the limit of detection (LOD) for DPV and CV as 0.1 and 0.3 µM, respectively. The outstanding outcome of the sensor is attributed to the 2D Cu-TCPP(Ni) MOF nanosheet's substantial active surface area, innate catalytic activity, and superior adsorption capacity. Furthermore, it is anticipated that the proposed electrode sensor will make it possible to create high-performance electrochemical sensors for environmental point-of-care testing since it successfully detected p-NP in real sample analysis.

Hydrogel-Functionalized Bandages with Janus Wettability for Efficient Unidirectional Drug Delivery and Wound Care.

Chronic wounds have imposed a severe physical and economic burden on the global healthcare system, which are usually treated by the delivery of drugs or bioactive molecules to the wound bed through wound dressings. In this work, we have demonstrated a hydrogel-functionalized bandage with Janus wettability in a bilayer structure to achieve unidirectional drug delivery and multifunctional wound care. The Janus patterned bandage with porous gradient wetting channels on the upper layer is responsible for the unidirectional transport of the drug from the outside to the wound bed (up to 90% drug transport efficiency) while preventing drug diffusion in unwanted directions (<8%). The hydrogel composed of chitosan quaternary ammonium salt (HACC), poly(vinyl alcohol) (PVA), and poly(acrylic acid) (PAA) at the bottom layer further functionalized such a bandage with biocompatibility, excellent antibacterial properties, and hemostatic ability to promote wound healing. Especially, the hydrogel-functionalized bandage with Janus wettability exhibits excellent mechanical flexibility (∼198% strain), which can comply well with skin deformation (stretching, bending, or twisting) and maintain unidirectional drug delivery behavior without any leakage. The in vivo full-thickness skin wound model confirms that the hydrogel-functionalized bandage can significantly facilitate epithelialization and collagen deposition and improve drug delivery efficiency, thus promoting wound closure and healing (the wound healing ratio was 98.10% at day 15). Such a synergistic strategy of unidirectional drug delivery and multifunctional wound care provides a more efficient, economical, and direct method to promote wound healing, which could be used as a potential high-performance wound dressing for clinical application.

Photothermal-driven micro/nanomotors: From structural design to potential applications.

Micro/nanomotors (MNMs) that accomplish autonomous movement by transforming external energy into mechanical work are attractive cargo delivery vehicles. Among various propulsion mechanisms of MNMs, photothermal propulsion has gained considerable attention because of their unique advantages, such as remote, flexible, accurate, biocompatible, short response time, etc. Moreover, besides as a propulsion source, the light has been extensively investigated as an excitation source in bioimaging, photothermal therapy (PTT), photodynamic therapy (PDT) and so on. Furthermore, the geometric topology and morphology of MNMs have a tremendous impact on improving their performance in motion behavior under NIR light propulsion, environmental suitability and functional versatility. Hence, this review article provides a comprehensive overview of structural design principles and construction strategies of photothermal-driven MNMs, and their emerging nanobiomedical applications. Finally, we further provide an outlook towards prospects and challenges during the development of photothermal-driven MNMs in the future. STATEMENT OF SIGNIFICANCE: Photothermal-driven micro/nanomotors (MNMs) that are regarded as functional cargo delivery tools have gained considerable attention because of unique advantages in propulsion mechanisms, such as remote, flexible, accurate and fully biocompatible light manipulation and extremely short light response time. The geometric topology and morphology of MNMs have a tremendous impact on improving their performance in motion behavior under NIR light propulsion, environmental suitability and functional versatility of MNMs. There are no reports about the review focusing on photothermal-driven MNMs up to now. Herein, we systematically review the latest progress of photothermal-driven MNMs including design principle, fabrication strategy of various MNMs with different structures and nanobiomedical applications. Moreover, the summary and outlook on the development prospects and challenges of photothermal-driven MNMs are proposed, hoping to provide new ideas for the future design of photothermal-driven MNMs with efficient propulsion, multiple functions and high biocompatibility.

Machine Learning-Assisted Janus Colorimetric Face Mask for Breath Ammonia Analysis.

Artificial olfactory systems have been widely used in medical fields such as in the analysis of volatile organic compounds (VOCs) in human exhaled breath. However, there is still an urgent demand for a portable, accurate breath VOC analysis system for the healthcare industry. In this work, we proposed a Janus colorimetric face mask (JCFM) for the comfortable evaluation of breath ammonia levels by combining the machine learning K-nearest neighbor (K-NN) algorithm. Such a Janus fabric is designed for the unidirectional penetration of exhaled moisture, which can reduce stickiness and ensure facial dryness and comfort. Four different pH indicators on the colorimetric array serve as recognition elements that cross-react with ammonia, capturing the optical fingerprint information on breath ammonia by mimicking the sophisticated olfactory structure of mammals. The Euclidean distance (ED) is used to quantitatively describe the ammonia concentration between 1 ppm and 10 ppm, indicating that there is a linear relationship between the ammonia concentration and the ED response (R2 = 0.988). The K-NN algorithm based on RGB response features aids in the analysis of the target ammonia level and achieves a prediction accuracy of 96%. This study integrates colorimetry, Janus design, and machine learning to present a wearable and portable sensing system for breath ammonia analysis.

Fully Integrated Ratiometric Fluorescence Enrichment Platform for High-Sensitivity POC Testing of Salivary Cancer Biomarkers.

The point-of-care (POC) testing of cancer biomarkers in saliva with both high sensitivity and accuracy remains a serious challenge in modern clinical medicine. Herein, we develop a new fully integrated ratiometric fluorescence enrichment platform that utilizes acoustic radiation forces to enrich dual-emission sandwich immune complexes for a POC visual assay. As a result, the color signals from red and green fluorescence (capture probe and report probe, respectively) are enhanced by nearly 10 times, and colorimetric sensitivity is effectively improved. When illuminated using a portable UV lamp, the fluorescence color changing from red to green can be clearly seen with the naked eye, which allows a semiqualitative assessment of the carcinoembryonic antigen (CEA) level. In combination with a homemade smartphone-based portable device, cancer biomarkers like CEA are quantified, achieving a limit of detection as low as 0.012 ng/mL. We also directly quantify CEA in human saliva samples to investigate the reliability of this fully integrated platform, thus validating the usefulness of the proposed strategy for clinical diagnosis and home monitoring of physical conditions.

Emerging open-channel droplet arrays for biosensing.

Open-channel droplet arrays have attracted much attention in the fields of biochemical analysis, biofluid monitoring, biomarker recognition and cell interactions, as they have advantages with regard to miniaturization, parallelization, high-throughput, simplicity and accessibility. Such droplet arrays not only improve the sensitivity and accuracy of a biosensor, but also do not require sophisticated equipment or tedious processes, showing great potential in next-generation miniaturized sensing platforms. This review summarizes typical examples of open-channel microdroplet arrays and focuses on diversified biosensing integrated with multiple signal-output approaches (fluorescence, colorimetric, surface-enhanced Raman scattering (SERS), electrochemical, etc.). The limitations and development prospects of open-channel droplet arrays in biosensing are also discussed with regard to the increasing demand for biosensors.

Ultrasound-enhanced catalytic hairpin assembly capable of ultrasensitive microRNA biosensing for the early screening of Alzheimer's disease.

Catalytic hairpin assembly (CHA) is a promising enzyme-free, isothermal signal amplification strategy, but the relatively time-consuming strand replacement limits its application scenarios. Here, we developed an ultrasound-enhanced catalytic hairpin assembly (UECHA) biosensing platform for early screening of Alzheimer's disease by introducing a portable acoustic-drive platform with functionalized microspheres for effective biomarkers enrichment and fluorescence enhancement. By constructing a gradient ultrasonic field in a microcavity, the platform concentrates the functionalized microspheres in a central position, accompanied by an enhanced fluorescence signal with a specific release. In addition, the programmable frequency modulation can also modify the acoustic potential well and effectively promote non-equilibrium chemical reactions such as CHA (25 min). Compared with the conventional catalytic hairpin assembly (CHA), UECHA allows for direct and quantitative measurement of AD miRNAs down to 3.55 × 10-15 M in 1 µL samples. This visual analysis of ultra-trace biomarkers based on acoustic enrichment and promotion provides a new perspective for the rapid and highly sensitive clinical detection of Alzheimer's disease.

Advancements in artificial micro/nanomotors for nucleic acid biosensing: a review of recent progress.

Artificial micro/nanomotors represent a class of well-designed tools that exhibit dynamic motion and remote-control capabilities, endowing them with the capacity to perform complex tasks at the micro/nanoscale. Their utilization in nucleic acid biosensing has been paid significant attention, owing to their ability to facilitate targeted delivery of detection probes to designated sites and enhance hybridization between detection probes and target nucleic acids, thereby improving the sensitivity and specificity of biosensing. Within this comprehensive overview, we elucidate the advancement of nucleic acid biosensing through the integration of micro/nanomotors over the past decade. In particular, we provide an in-depth exploration of the diverse applications of micro/nanomotors in nucleic acid biosensing, including fluorescence recovery-based biosensing, velocity change-based biosensing, and aggregation-enhanced biosensing. Additionally, we outline the remaining challenges that impede the practical application of artificial micro/nanomotors in nucleic acid detection, and offer personal insights into prospective avenues for future development. By overcoming these obstacles, we anticipate that artificial micro/nanomotors will revolutionize conventional nucleic acid detection methodologies, providing enhanced sensitivity and reduced diagnostic timeframes, thereby facilitating more effective disease diagnosis.

Oriented Antibody-Assembled Metal-Organic Frameworks for Persistent Wearable Sweat Cortisol Detection.

The level of cortisol can reflect people's psychological stress, help diagnose adrenal gland diseases, and is also related to several mental diseases. In this study, we developed a cortisol monoclonal antibody-oriented approach to modify an immunosensor for wearable label-free and persistent sweat cortisol detection. On such an antibody-oriented immunosensor, the fragment crystallizable (Fc) region is partially inserted within the metal-organic framework (MOF), and antibody-binding regions of the cortisol monoclonal antibody (Cmab) were exposed on the MOF surface via selective growth and self-assembly. Such ordered and oriented embedding of antibodies in the MOF resulted in excellent antibody activity and improved stability and antigen-binding capacity. We also engineered the full integrated system for on-body sweat cortisol biosensing performance in several volunteers, and the results indicated that this wearable sensor is suitable for practical cortisol detection with a good linear detection range from 1 pg/mL to 1 µg/mL with a lower limit of detection of 0.26 pg/mL. Moreover, the wearable sensor demonstrated good persistence in detecting cortisol, with only 4.1% decay after 9 days of storage. The present work represents a simple oriented antibody assembling approach to improve the stability of antibodies, providing an important step toward long-term continuous sweat biomarker detection.

Programmable-Modulated Ultrasonic Transducer Array for Contactless Detection of Viral RNAs.

The current polymerase chain reactions-based nucleic acid tests for large-scale infectious disease diagnosis are always lab-dependent and generate large amounts of highly infectious plastic waste. Direct non-linear acoustic driven of microdroplets provide an ideal platform for contactless spatial and temporal manipulation of liquid samples. Here, a strategy to programmable-manipulate microdroplets using potential pressure well for contactless trace detection is conceptualized and designed. On such contactless modulation platform, up to seventy-two piezoelectric transducers are precisely self-focusing single-axis arranged and controlled, which can generate dynamic pressure nodes for effectively contact-free manipulating microdroplets without vessel contamination. In addition, the patterned microdroplet array can act as contactless microreactor and allow multiple trace samples (1-5 µL) biochemical analysis, and the ultrasonic vortex can also accelerate non-equilibrium chemical reactions such as recombinase polymerase amplification (RPA). The results of fluorescence detection indicated that such programmable modulated microdroplet achieved contactless trace nucleic acid detection with a sensitivity of 0.21 copy µL-1 in only 6-14 min, which is 30.3-43.3% shorter than the conventional RPA approach. Such a programmable containerless microdroplet platform can be used for toxic, hazardous, or infectious samples sensing, opening up new avenues for developing future fully automated detection systems.

Radiative cooling and anisotropic wettability in E-textile for comfortable biofluid monitoring.

Long-term wearing comfort is essential for future advanced electronic textiles (e-textiles). Herein, we fabricate a skin-comfortable e-textile for long-term wearing experience on human epidermis. Such e-textile was simply fabricated through two different dip coating methods and single-side air plasma treatment, which couples radiative thermal and moisture management for biofluid monitoring. The silk-based substrate with improved optical properties and anisotropic wettability can provide a temperature drop of 1.4 °C under strong sunlight. Moreover, the anisotropic wettability of the e-textile can provide a dryer skin microenvironment by comparing with traditional fabric. The fiber electrodes weaving into the inner side of the substrate can noninvasively monitor multiple sweat biomarkers (i.e., pH, uric acid, and Na+). Such a synergistic strategy may pave a new path to design next-generation e-textiles with significantly improved comfort.

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.