Rare Earth-Carbon Dots Nanocomposite-Modified Glass Nanopipettes: Electro-Optical Detection of Bacterial ppGpp.

As an important alarmone nucleotide, guanosine 3'-diphosphate-5'-diphosphate (ppGpp) can regulate the survival of bacteria under strict environmental conditions. Direct detection of ppGpp in bacteria with high sensitivity and selectivity is crucial for elucidating the role of ppGpp in bacterial stringent response. Herein, the terbium-carbon dots nanocomposite (CDs-Tb) modified glass nanopipet was developed for the recognition of ppGpp. The CDs-Tb in glass nanopipette preserved their fluorescence properties as well as the coordination capacity of Tb3+ toward ppGpp. The addition of ppGpp not only led to the fluorescence response of CDs-Tb but also triggered variations of surface charge inside the glass nanopipet, resulting in the ionic current response. Compared with nucleotides with similar structures, this method displayed good selectivity toward ppGpp. Moreover, the dual signals (fluorescence and ionic current) offered a built-in correction for potential interference. Apart from the high selectivity, the proposed method can determine the concentration of ppGpp from 10-13 to 10-7 M. Taking advantage of the significant analytical performance, we monitored ppGpp in Escherichia coli under different nutritional conditions and studied the relationship between ppGpp and DNA repair, which is helpful for overcoming antibiotic resistance and promoting the development of potential drugs for antibacterial treatment.

Ultrasensitive sensing urinary cystatin C via an interface-engineered graphene extended-gate field-effect transistor for non-invasive diagnosis of chronic kidney disease.

Early chronic kidney disease (CKD) has strong concealment and lacks an efficient, non-invasive, and lable-free detection platform. Cystatin C (Cys C) in urine is closely related to the progress of CKD (especially at the early stage), which is an ideal endogenous marker to evaluate the impairment of renal function. Thus, the accurate detection of urinary Cys C (u-Cys C) is great significant for early prevention and treatment and delaying the course of the disease of CKD patients. Herein, we developed an extended-gate field-effect transistor (EG-FET) sensor for ultrasensitive detection of u-Cys C, which consists of a monolithic interface-engineered graphene EG electrode array and a commercially available MOSFET. Laser-induced graphene (LIG) loaded with sputtered Au NPs in the presence of adhesive Cr (Au NPs/Cr/LIG) boosts the electrical performance of the EG electrode. Meanwhile, Au NPs also serve as linkers to immobilize papain that can selectively form protein complexes with Cys C. Supported by the synergistic effect of multilevel interface-engineered graphene, our sensor exhibits a good linear correlation within the u-Cys C concentration range of 5 ag/µL to 50 ng/µL with low detection limit of 0.05 ag/µL. Our work makes accurate, specific and rapid detection of u-Cys C feasible and promising for early screening for CKD.

Room temperature cost-effective synthesis of carbon quantum dots for fluorescence pattern recognition of metal ions.

Herein, a type of low-consuming carbon quantum dot (CD) has been synthesized at room temperature in just 45 minutes via Schiff base reaction between o-phthalaldehyde (OPA) and polyethyleneimine (PEI). These CDs are pH-dependent, so a novel label-free florescent sensor array can be constructed by utilizing buffers with various pH levels, which leads to distinctive fluorescence response patterns upon being challenged with metal ions for their pattern recognition. The results demonstrate that large-scale detection of metal ions can be achieved with as little as 3 types of sensors. Additionally, the sensors are able to discriminate between various metal ion concentrations and mixtures of different metal ions. The technique demonstrates potential uses in water quality monitoring by promising straightforward, quick, sensitive, and potent discrimination of metal ions.

Multi-engineered Graphene Extended-Gate Field-Effect Transistor for Peroxynitrite Sensing in Alzheimer's Disease.

The expression of ß-amyloid peptides (Aß), a pathological indicator of Alzheimer's disease (AD), was reported to be inapparent in the early stage of AD. While peroxynitrite (ONOO-) is produced excessively and emerges earlier than Aß plaques in the progression of AD, it is thus significant to sensitively detect ONOO- for early diagnosis of AD and its pathological research. Herein, we unveiled an integrated sensor for monitoring ONOO-, which consisted of a commercially available field-effect transistor (FET) and a high-performance multi-engineered graphene extended-gate (EG) electrode. In the configuration of the presented EG electrode, laser-induced graphene (LIG) intercalated with MnO2 nanoparticles (MnO2/LIG) can improve the electrical properties of LIG and the sensitivity of the sensor, and graphene oxide (GO)-MnO2/Hemin nanozyme with ONOO- isomerase activity can selectively trigger the isomerization of ONOO- to NO3-. With this synergistic effect, our EG-FET sensor can respond to the ONOO- with high sensitivity and selectivity. Moreover, taking advantage of our EG-FET sensor, we modularly assembled a portable sensing platform for wireless tracking ONOO- levels in the brain tissue of AD transgenic mice at earlier stages before massive Aß plaques appeared, and we systematically explored the complex role of ONOO- in the occurrence and development of AD.

Continuous Preparation of Semiconducting Polymer Nanoparticles with Varied Sizes for Online Fluorescence Sensing via a Laser-Tailored 3D Microfluidic Chip.

Microfluidic chips are in critical demand for emerging applications in material synthesis and biosensing. Herein, we relied on ultrafast laser-processing technology to fabricate a three-dimensional (3D) microfluidic chip, in which semiconducting polymer nanoparticles (SPNs) were continuously synthesized with tunable size and SPN-involved online fluorescence sensing was implemented. A homogeneous distribution of SPNs can be readily realized due to the efficient mixing and powerful vortices of the 3D microfluidic chip, which prevents SPNs from aggregating throughout the synthesis process. Moreover, in the optimized conditions, we unveiled unique SPNs with an ultrasmall particle size (<3 nm) and good monodispersity. By integrating with the high-performance fluorescence of SPNs and 3D microfluidic chip, we further developed an online sensing platform for ratiometric fluorescence assays of H2O2 and oxidase-catalyzed substrates (e.g., glucose), in which a composite of SPNs and neutral red (NR) (SPNs/NR) was used as the mediator. The limit of detection (LOD) for H2O2 is 0.48 µM, and the LOD for glucose is 3.33 µM via the presented platform. This 3D microfluidic synthesis-and-sensing platform provides a new avenue for the facile production of nanoparticles and offers exciting prospects in the field of online sensing biomarkers.

Tailoring Food Biopolymers into Biogels for Regenerative Wound Healing and Versatile Skin Bioelectronics.

An increasing utilization of wound-related therapeutic materials and skin bioelectronics urges the development of multifunctional biogels for personal therapy and health management. Nevertheless, conventional dressings and skin bioelectronics with single function, mechanical mismatches, and impracticality severely limit their widespread applications in clinical. Herein, we explore a gelling mechanism, fabrication method, and functionalization for broadly applicable food biopolymers-based biogels that unite the challenging needs of elastic yet injectable wound dressing and skin bioelectronics in a single system. We combine our biogels with functional nanomaterials, such as cuttlefish ink nanoparticles and silver nanowires, to endow the biogels with reactive oxygen species scavenging capacity and electrical conductivity, and finally realized the improvement in diabetic wound microenvironment and the monitoring of electrophysiological signals on skin. This line of research work sheds light on preparing food biopolymers-based biogels with multifunctional integration of wound treatment and smart medical treatment.

Au/Lum/RhB@Ag-DMcT ICP-Based Double-Ratio Colorimetric and Fluorometric Dual Mode Assay and Multi-Responsive Coffee Ring Chips for Point-of-Use Analysis of Phosphate Ions.

In this work, by fully exploring the stimulus response of the guest-functionalized infinite coordination polymers (ICPs), a double-ratio colorimetric and fluorometric dual mode assay and multi-responsive coffee ring chips for point-of-use analysis of phosphate ions (Pi) were proposed. First, the complex host-guest interactions were rationally designed to obtain Au/Lum/RhB@Ag-DMcT ICPs. The composite ICPs exhibited a purple-blue color resulted from the modulated localized surface plasmon resonance (LSPR) of the Au core, and a blue fluorescence color stemmed from the unique aggregation-induced-emission (AIE) of Luminol (Lum) and the aggregation-caused-quenching (ACQ) of rhodamine B (RhB). With the presence of Pi, the host-guest interactions of the shell within Au/Lum/RhB@Ag-DMcT ICPs were interrupted to release Au core, Lum, and RhB in a dispersed state. Consequently, the color of the solution changed to purple-red (the mixed color of the Au core and RhB guest), and the fluorescence color turned to orange-red (AIE of Lum decreased, while the ACQ of RhB recovered). This constituted the sensing mechanism for dual-mode Pi assay with the double ratiometric response. Second, during the stimulus response, the surface wettability/size/amount of Au/Lum/RhB@Ag-DMcT ICPs simultaneously altered. These changes were reflected in the form of the coffee ring deposition pattern variances on the glass substrate and served as signal readouts for the exploration of multi-responsive coffee ring chips for the first time. Quantitative Pi detection with high accuracy and reliability in real samples was thereby realized, which offered an opportunity for the point-of-use analysis of Pi in resources-limited areas in a high-throughput fashion.

Wearable Clinic: From Microneedle-Based Sensors to Next-Generation Healthcare Platforms.

The rapid development of wearable biosensing calls for next-generation devices that allow continuous, real-time, and painless monitoring of health status along with responsive medical treatment. Microneedles have exhibited great potential for the direct access of dermal interstitial fluid (ISF) in a minimally invasive manner. Recent studies of microneedle-based devices have evolved from conventional off-line detection to multiplexed, wireless, and integrated sensing. In this review, the classification and fabrication techniques of microneedles are first introduced, and then the representative examples of microneedles for transdermal monitoring with different sensing modalities are summarized. State-of-the-art advances in therapeutic and closed-loop systems are presented to formulate guidelines for the development of next-generation microneedle-based healthcare platforms. The potential challenges and prospects are discussed to pave a new avenue toward pragmatic applications in the real world.

Ultrasensitive therapeutic drug monitoring of methotrexate by a structure-switching aptamer with cascade primer exchange reaction.

As a folate antagonist, methotrexate (MTX) has been widely used in clinics with good effects on various tumors and inflammatory diseases. While the optimum dosage and total body clearance of MTX usually varies between individuals and even low-dose MTX has side effects, high-dose MTX may cause life-threatening side effects. Therefore, a convenient and simple method toward MTX sensing is highly demanded. Herein, we report a highly sensitive and selective method for therapeutic drug monitoring (TMD) of MTX by integrating a highly specific MTX-dependent structure-switching aptamer with a primer exchange reaction-based signal amplification technique. The detection limit is down to 1.7 nM with a linear range from 0.01 to 1 µM in buffer. More importantly, the sensing strategy can effectively detect MTX in a complex bio-environment with a linear response range from 0.05 to 2 µM and a LOD of 12.4 nM in 10% FBS and a range of 0.2 to 5 µM with a LOD of 63.73 nM in 10% whole blood. Considering the high sensitivity and selectivity and good performance in blood, the method reported herein paves a new avenue for the effective determination of MTX in clinics.

Stimuli-responsive polymers for interface engineering toward enhanced electrochemical analysis of neurochemicals.

Neurochemical monitoring can provide important insights into the chemical communications in the brain and neurological diseases. Although electrochemical sensors have promoted the development of neurochemical analysis, the limited analytical performance of the existing sensors restrict our understanding of the roles that chemical signals play in the brain. The central nervous system is composed of a large number of neurochemical species. Meanwhile, it is difficult to monitor neurochemicals with high sensitivity because of the kinetic barrier of mass transport and electron/ion transfer. More importantly, to fabricate a "smart" electrochemical sensor for neurochemicals, the engineering of an electrode surface with switchable properties and a response is urgently needed. This review focuses on the construction and application of electrochemical sensors based on stimuli-responsive polymers. The response of polymers to external stimuli can not only enhance the target recognition, but also modulate the electrochemical signals, thus providing smart electrochemical sensing platform with improved analytical performance, including high selectivity, sensitivity, and controllability. In this review, we first introduce the design strategy of bio-responsive stimuli-responsive polymers and highlight the relationship between their structure and molecular recognition efficiency. Then, we summarize the electrochemical techniques with different sensing principles and emphasize the contribution that stimuli-responsive polymers made to the conversion of chemical/electrochemical reactions into electric signals. Finally, the opportunities and limitations of stimuli-responsive polymer-modified electrochemical sensors for neurochemical analysis will be discussed. Taking advantage of the development of novel materials, electrochemical techniques and microelectronic engineering, the advanced devices (e.g., antifouling, flexible, miniaturized, and multi-functional) with remarkable analytical performance will benefit the evaluation of neurochemicals, which can promote a deep understanding of brain events and the diagnosis and treatment of neurological diseases.

Modular Assembly of MXene Frameworks for Noninvasive Disease Diagnosis via Urinary Volatiles.

Volatile organic compounds (VOCs) in urine are valuable biomarkers for noninvasive disease diagnosis. Herein, a facile coordination-driven modular assembly strategy is used for developing a library of gas-sensing materials based on porous MXene frameworks (MFs). Taking advantage of modules with diverse composition and tunable structure, our MFs-based library can provide more choices to satisfy gas-sensing demands. Meanwhile, the laser-induced graphene interdigital electrodes array and microchamber are laser-engraved for the assembly of a microchamber-hosted MF (MHMF) e-nose. Our MHMF e-nose possesses high-discriminative pattern recognition for simultaneous sensing and distinguishing of complex VOCs. Furthermore, with the MHMF e-nose being a plug-and-play module, a point-of-care testing (POCT) platform is modularly assembled for wireless and real-time monitoring of urinary volatiles from clinical samples. By virtue of machine learning, our POCT platform achieves noninvasive diagnosis of multiple diseases with a high accuracy of 91.7%, providing a favorable opportunity for early disease diagnosis, disease course monitoring, and relevant research.

Aptamer-engineered extended-gate field-effect transistor device for point-of-care therapeutic drug monitoring.

Herein, we report a portable point-of-care testing (POCT) device based on an aptamer-engineered extended-gate field-effect transistor (EG-FET) for therapeutic monitoring of the drug methotrexate. This method was shown to be highly sensitive, efficient, and convenient to use, features contributing to its realizing a clinical detection of drugs in blood.

Debonding-On-Demand Polymeric Wound Patches for Minimal Adhesion and Clinical Communication.

Herein, a multifunctional bilayer wound patch is developed by integrating a debonding-on-demand polymeric tissue adhesive (DDPTA) with an ionic conducting elastomer (ICE). As a skin adhesive layer, the DDPTA is soft and adherent at skin temperature but hard and non-tacky when cooled, so it provides unique temperature-triggered quick adhesion and non-forced detachment from the skin. During use, the dense surface of the DDPTA prevents blood infiltration and reduces unnecessary blood loss with gentle pressing. Moreover, its hydrophobic matrix helps to repel blood and prevents the formation of clots, thus precluding wound tearing during its removal. This unique feature enables the DDPTA to avoid the severe deficiencies of hydrophilic adhesives, providing a reliable solution for a wide range of secondary wound injuries. The DDPTA is versatile in that it can be covered with ICE to configure a DDPTA@ICE patch for initiating non-verbal communication systems by the fingers, leading toward sign language recognition and a remote clinical alarm system. This multifunctional wound patch with debonding-on-demand can promote a new style of tissue sealant for convenient clinical communication.

Rational design of MoS2 QDs and Eu3+ as a ratiometric fluorescent probe for point-of-care visual quantitative detection of tetracycline via smartphone-based portable platform.

The abuse of the antibiotic tetracycline (TC) has resulted in its residues in the environment and animals, which has caused irreversible damage to public health safety and environments. Therefore, it is urgently needed to develop alternative sensitive and low-cost for quickly and accurately detection the TC residues in the environments. We innovatively rational design of MoS2 QDs and Eu3+ to construct ratiometric fluorescent probe to detect TC. In general, TC coordinates Eu3+ to form Eu-TC coordination compound with weak luminescence. However, MoS2 QDs with exceptional fluorescence characteristics are a good energy donors and acceptors, MoS2 QDs can transfer energy with Eu-TC coordination compound, which can greatly enhance the luminous ability of Eu-TC coordination compound while accompanied by a decline of its initial fluorescence intensity. MoS2 QDs can be used as an indicator and enhancer in the MoS2-Eu3+ ratiometric probe, which can greatly improve limit of detection and accuracy of quantitation for TC. The detection of TC by fluorescent intensity ratio (F620/F470) of MoS2 QDs-Eu3+ shows a good linear response in the range of 10 nM-60 µM TC, with the limit of detection (LOD) toward TC is calculated to be 2 nM (3σ/slope), the recovery is 94.4-108.4%, and the RSD is less than 5.36. The smartphone-based portable platform with the RGB color recognition software is designed for point-of-care visual quantitative detection of TC. The portable detection system shows a low detection limit (0.05 µM) and excellent reproducibility in the range of 1-40 µM TC. This work has provided a sensitive, rapid, real-time detection of environmental pollutants.

Wound Dressing: From Nanomaterials to Diagnostic Dressings and Healing Evaluations.

Wound dressings based on nanomaterials play a crucial role in wound treatment and are widely used in a whole range of medical settings, from minor to life-threatening tissue injuries. This article presents an educational review on the accumulating knowledge in this multidisciplinary area to lay out the challenges and opportunities that lie ahead and ignite the further and faster development of clinically valuable technologies. The review analyzes the functional advantages of nanomaterial-based gauzes and hydrogels as well as hybrid structures thereof. On this basis, the review presents state-of-the-art advances to transfer the (semi)blind approaches to the evaluation of a wound state to smart wound dressings that enable real-time monitoring and diagnostic functions that could help in wound evaluation during healing. This review explores the translation of nanomaterial-based wound dressings and related medical aspects into real-world use. The ongoing challenges and future opportunities associated with nanomaterial-based wound dressings and related clinical decisions are presented and reviewed.

Rational design of a self-assembled surfactant film in nanopipettes: combined fluorescence and electrochemical sensing.

Herein, a generalizable method based on the formation of a self-assembled surfactant film was reported to build a nanopipette system. Using this nanopipette, it was found that arginine metabolism shows an age-related difference in Alzheimer's disease.

High-Performance Extended-Gate Field-Effect Transistor for Kinase Sensing in Aß Accumulation of Alzheimer's Disease.

An amyloid-beta peptide (Aß) is generally believed to be a pathological marker of Alzheimer's disease (AD), but it is still of great significance to explore the upstream and downstream relationship of Aß in AD. It is previously reported that c-Abl, a nonreceptor tyrosine kinase, can be activated by Aß, but the interaction between Aß and c-Abl is still unknown. Herein, an extended-gate field-effect transistor (EG-FET)-based sensor has been developed to monitor the level of c-Abl with high sensitivity and selectivity. Our peptide-functionalized EG-FET sensor as the signal transducer can follow c-Abl activity with electron transfer by its specific phosphorylation. The sensor presents a good linear correlation over c-Abl concentrations of 1 pg/mL to 3.05 µg/mL. The sensor was successfully applied to quantify c-Abl activity in the brain tissue of AD transgenic mice, and the interaction between c-Abl and Aß in AD mice was explored by administering the c-Abl inhibitor (imatinib) and the agonist (DPH). Our work is expected to provide an important reference for early diagnosis and treatment of AD.

Interface engineering with self-assembling Au@Ag@ß-cyclodextrin bimetal nanoparticles to fabricate a ring-like arrayed SERS substrate for sensitive recognition of phthalate esters based on a host-guest interaction and the coffee ring effect.

Herein, Au@Ag@ß-cyclodextrin (ß-CD) nanoparticles with a relatively uniform shape and size of ∼13 nm in diameter have been successfully synthesized, and the surfaces of the synthesized nanoparticles are successful modified by ß-CD. A highly efficient synthetic approach was developed for the preparation of a surface-enhanced Raman spectroscopy (SERS) substrate, which self-assembles Au@Ag@ß-CD nanoparticles and analytes into a coffee ring pattern via the coffee ring effect. The coffee ring effect can make phthalates (PAEs) aggregate to the edge together with the Au@Ag@ß-CD nanoparticles and concentration enrichment can be achieved. In addition, the surface of the core-shell Au@Ag@ß-CD is modified with ß-CD with a cavity structure, which can enrich analyte concentration by adsorbing the analytes into the hydrophobic cavity using host-guest recognition. This enrichment process not only improves the concentration of the surface of the analyte but also effectively distinguishes it from other substances in the analyte solution. The mechanism of enrichment and host-guest recognition is verified by subsequent molecular docking simulation. Thus, a ring-like arrayed SERS substrate with dual-strategy enrichment is used to detect PAEs. The experiments using the ring-like arrayed SERS substrate, gave a limit of detection of 0.2 nM for DOP detection, the recovery rate of the spiked samples ranged from 92.3% to 106.6%, and an RSD of less than 6% for PAE detection is obtained. This work provided a simple, rapid, low-cost, highly sensitive and stable method for PAE detection in life and the environment.

Lanthanide metal-organic framework as a paper strip sensor for visual detection of sulfonamide with smartphone-based point-of-care platform.

Antibiotic residues in aquatic environments have attracted wide attention. Considering the impacts on the ecosystem and human health, it is urgent to develop a rapid method for detecting antibiotic residues in the environment. In this work, a nanoscale lanthanide metal-organic framework Eu(TATB) with a stable red luminescence in aqueous solution is synthesized by the microemulsion method. Sulfamethazine (SMZ) is frequently most used in veterinary medicine as one of sulfonamides. Eu(TATB) can be used for sensitively and rapidly specific recognition of SMZ with low detection limit (0.67 µM) and eminent recyclability. In addition, a paper-based visual system for point-of-care (POC) monitoring SMZ is devised by both using filter paper embedded with Eu(TATB) and our developed portable smartphone-involved imaging cassette. The naked eyes can observe that the red luminescence of the paper sensor gradually fades away at the presence of SMZ. This provides a reliable and effective method for on-site detection of sulfonamide antibiotics in the field of environmental monitoring.

Progress on the reaction-based methods for detection of endogenous hydrogen sulfide.

Hydrogen sulfide (H2S) is a biologically signaling molecule that mediates a wide range of physiological functions, which is frequently misregulated in numerous pathological processes. As such, measurement of H2S holds great attention due to its unique physiological and pathophysiological roles. Currently, a variety of methods based on the H2S-involved reactions have been reported for detection of endogenous H2S, bearing the advantages of good specificity and high sensitivity. This review describes in detail the types of reactions, their mechanisms, and their applications in biological research, thus hopefully providing some guidelines to the researchers in this field for further investigation.