An immune sandwich electrochemical biosensor based on triple-modified zirconium derivatives for detection of CD146 in serum.

CD146, also known as melanoma cell adhesion molecule (MCAM), is overexpressed in various cancer patients, making it a valuable predictor for early diagnosis. In this work, an immune sandwich electrochemical biosensor is proposed for sensitive and non-invasive quantitative detection of CD146 in serum. Zirconium-based MOF (UIO-66) was modified by simultaneous copper atom doping, in situ growth carbon-based support and physical embedding of platinum nanoparticles (PtNPs). Triple-modified Cu-UIO-66@SWCNT/PtNPs nanocomposites with high stability and excellent electrochemical properties, serve as surface modification materials for glassy carbon electrodes. Anti-CD146 antibody (Ab1) was grafted onto the electrode surface via Pt-S bond. Meanwhile, the secondary antibody (Ab2) was conjugated with silver nanoparticles (AgNPs) to cooperate for CD146 capture and achieve secondary electrical signal amplification. Under optimal conditions, square wave voltammetry was employed to determine CD146 in the concentration range of 10-9-10-4 mg/mL and a limit of detection of 12 fg/mL was obtained. Finally, it was successfully applied to the analysis of CD146 in lung and liver cancer patients' serum samples.

CRISPR/Cas and Argonaute-Based Biosensors for Pathogen Detection.

Over the past few decades, pathogens have posed a threat to human security, and rapid identification of pathogens should be one of the ideal methods to prevent major public health security outbreaks. Therefore, there is an urgent need for highly sensitive and specific approaches to identify and quantify pathogens. Clustered Regularly Interspaced Short Palindromic Repeats CRISPR/Cas systems and Argonaute (Ago) belong to the Microbial Defense Systems (MDS). The guided, programmable, and targeted activation of nucleases by both of them is leading the way to a new generation of pathogens detection. We compare these two nucleases in terms of similarities and differences. In addition, we discuss future challenges and prospects for the development of the CRISPR/Cas systems and Argonaute (Ago) biosensors, especially electrochemical biosensors. This review is expected to afford researchers entering this multidisciplinary field useful guidance and to provide inspiration for the development of more innovative electrochemical biosensors for pathogens detection.

Correction: Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications.

Correction for 'Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications' by Chonglu Li et al., Chem. Soc. Rev., 2023, 52, 4392-4442, https://doi.org/10.1039/D3CS00227F.

Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications.

Metal agents have made incredible strides in preclinical research and clinical applications in recent years, but their short emission/absorption wavelengths continue to be a barrier to their distribution, therapeutic action, visual tracking, and efficacy evaluation. Nowadays, the near-infrared window (NIR, 650-1700 nm) provides a more accurate imaging and treatment option. Thus, there has been ongoing research focusing on developing multifunctional NIR metal agents for imaging and therapy that have deeper tissue penetration. The design, characteristics, bioimaging, and therapy of NIR metal agents are covered in this overview of papers and reports published to date. To start with, we focus on describing the structure, design strategies, and photophysical properties of metal agents from the NIR-I (650-1000 nm) to NIR-II (1000-1700 nm) region, in order of molecular metal complexes (MMCs), metal-organic complexes (MOCs), and metal-organic frameworks (MOFs). Next, the biomedical applications brought by these superior photophysical and chemical properties for more accurate imaging and therapy are discussed. Finally, we explore the challenges and prospects of each type of NIR metal agent for future biomedical research and clinical translation.

Electrochemical signal amplification strategy based on trace metal ion modified WS2 for ultra-sensitive detection of miRNA-21.

Previous researches have suggested the potential correlation between the development of breast cancer and the concentration of miRNA-21 in serum. Theoretically the doping of multivalent metal ions in WS2 could bring higher electron transfer capacity, but this hasn't been proven. To fill this research gap, through one-pot method we prepared seven nanocomposite structures modified with different metal ions (Co2+, Ni2+, Mn2+, Zn2+, Fe3+, Cr3+, La3+). Characterization revealed that ammonia produced by hydrothermal urea exfoliated the multilayer graphene oxide (MGO) and provided a nitrogen source for doping reduction to form a 3D flower-like structure (NrGOF) with high specific surface area. Meanwhile, the modification of WS2 by Fe3+ not only enhanced its electrochemical conductivity but also gave the material an additional peroxidase activity centre. In the composite Fe3+-WS2/NrGOF-AgNPs, NrGOF is used as a conductive loading interface for WS2, while Fe3+ served as the catalytic and electron transfer centre for secondary amplification of the electrochemical signal. The experimental results showed that the sensing platform has a low limit of detection (LOD) of 1.18 aM for miRNA-21 in the concentration range of 10-17-10-12 M and has been successfully applied to the detection of real serum samples.

Ultrasound super-resolution imaging for the differential diagnosis of thyroid nodules: A pilot study.

Objective: Ultrasound imaging provides a fast and safe examination of thyroid nodules. Recently, the introduction of super-resolution imaging technique shows the capability of breaking the Ultrasound diffraction limit in imaging the micro-vessels. The aim of this study was to evaluate its feasibility and value for the differentiation of thyroid nodules. Methods: In this study, B-mode, contrast-enhanced ultrasound, and color Doppler flow imaging examinations were performed on thyroid nodules in 24 patients. Super-resolution imaging was performed to visualize the microvasculature with finer details. Microvascular flow rate (MFR) and micro-vessel density (MVD) within thyroid nodules were computed. The MFR and MVD were used to differentiate the benign and malignant thyroid nodules with pathological results as a gold standard. Results: Super-resolution imaging (SRI) technique can be successfully applied on human thyroid nodules to visualize the microvasculature with finer details and obtain the useful clinical information MVD and MFR to help differential diagnosis. The results suggested that the mean value of the MFR within benign thyroid nodule was 16.76 ± 6.82 mm/s whereas that within malignant thyroid was 9.86 ± 4.54 mm/s. The mean value of the MVD within benign thyroid was 0.78 while the value for malignant thyroid region was 0.59. MFR and MVD within the benign thyroid nodules were significantly higher than those within the malignant thyroid nodules respectively (p < 0.01). Conclusions: This study demonstrates the feasibility of ultrasound super-resolution imaging to show micro-vessels of human thyroid nodules via a clinical ultrasound platform. The important imaging markers, such as MVD and MFR, can be derived from SRI to provide more useful clinical information. It has the potential to be a new tool for aiding differential diagnosis of thyroid nodules.

Ultrasound Molecular Imaging and Its Applications in Cancer Diagnosis and Therapy.

Ultrasound imaging is regarded as a highly sensitive imaging modality used in routine clinical examinations. Over the last several decades, ultrasound contrast agents have been widely applied in ultrasound molecular cancer imaging to improve the detection, characterization, and quantification of tumors. To date, a few new potential preclinical and clinical applications regarding ultrasound molecular cancer imaging are being investigated. This review presents an overview of the various kinds of ultrasound contrast agents employed in ultrasound molecular imaging and advanced imaging techniques using these contrast agents. Additionally, we discuss the recent enormous development of ultrasound contrast agents in the relevant preclinical and clinical applications, highlight the recent challenges which need to be overcome to accelerate the clinical translation, and discuss the future perspective of ultrasound molecular cancer imaging using various contrast agents. As a highly promising and valuable tumor-specific imaging technique, it is believed that ultrasound molecular imaging will pave an accurate and efficient way for cancer diagnosis.

A novel conductive nanocomposite-based biosensor for ultrasensitive detection of microRNA-21 in serum, using methylene blue as mediator.

MicroRNA-21 (miRNA-21) is a common biomarker with high expression in breast tumors. Therefore, sensitive detection of miRNA-21 is of great significance for clinical breast tumor diagnosis. A TH/rGO/CMK-3/AuNPs nanocomposite is composed of thionine (TH), reduced graphene oxide (rGO), ordered mesoporous carbon (CMK-3), and gold nanoparticles (AuNPs), which help to increase the specific surface area of a glassy carbon electrode (GCE) and to amplify the DPV signal. Meanwhile, methylene blue (MB) was combined with the capture probe guanine and absorbed by the composite material to mediate the differential pulse voltammetry (DPV) of the obtained miRNA biosensor. The current response decreased with increasing miRNA-21 concentration under optimal conditions. The biosensor responds to miRNA-21 in the 0.1fM-1 pM concentration range, and the detection limit (LOD) was 0.046 fM. Moreover, human serum samples were effectively detected utilizing the miRNA-21 biosensor with satisfactory results.

An ultrasensitive hairpin sensor based on g-C3N4 nanocomposite for the detection of miRNA-155 in breast cancer patient serum.

Achieving the early diagnosis of breast cancer, through ultrasensitive detection of tumor marker miRNA-155, is a significant challenge. Therefore, an ultrasensitive hairpin electrochemical biosensor based on graphite-like phase carbon nitride composite was proposed. In this paper, poly(D-glucosamine) (PDG) was used as a stabilizer and reducing agent to prepare gold nanoparticles at room temperature, and then a graphite-like phase with a two-dimensional lamellar structure carbon nitride was further combined with it to obtain the poly(D-glucosamine)/gold nanoparticles/graphite-like phase carbon nitride nanocomposite (PDG/AuNPs/g-C3N4), in order to achieve the goal of signal amplification. The specific hairpin capture probe (HP) that recognized and bound miRNA-155 was then grafted. The hairpin biosensor showed a linear range of 0.1 fM-1 pM with a detection limit of 0.05 fM using differential pulse voltammetry (DPV) electrochemical analysis. Furthermore, the excellent performance hairpin electrochemical biosensor had been applied to the detection of miRNA-155 in human serum samples with good recovery.

NIR-II bioimaging of small molecule fluorophores: From basic research to clinical applications.

Due to the low autofluorescence and deep-photo penetration, the second near-infrared region fluorescence imaging technology (NIR-II, 1000-2000 nm) has been widely utilized in basic scientific research and preclinical practice throughout the past decade. The most attractive candidates for clinical translation are organic NIR-II fluorophores with a small-molecule framework, owing to their low toxicity, high synthetic repeatability, and simplicity of chemical modification. In order to enhance the translation of small molecule applications in NIR-II bioimaging, NIR-II fluorescence imaging technology has evolved from its usage in cells to the diagnosis of diseases in large animals and even humans. Although several examples of NIR-II fluorescence imaging have been used in preclinical studies, there are still many challenges that need to be addressed before they can finally be used in clinical settings. In this paper, we reviewed the evolution of the chemical structures and photophysical properties of small-molecule fluorophores, with an emphasis on their biomedical applications ranging from small animals to humans. We also explored the potential of small-molecule fluorophores.

Near-Infrared Light Regulation of Capture and Release of ctDNA Platforms Based on the DNA Assembly System.

Despite recent progress, a challenge remains on how to gently release and recover viable ctDNA captured on DNA probe-based devices. Here, a reusable detector was successfully manufactured for the capture and release of ctDNA by means of an UCNPs@SiO2-Azo/CD-probe. Biocompatible NIR light is used to excite UCNPs and convert into local UV light. Continuous irradiation induces a rapid release of the entire ctDNA-probe-CD complex from the functionalized surface via the trans-cis isomerization of azo units without disrupting the ctDNA-structure receptor. Specifically, these composite chips allow reloading DNA probes for reusable ctDNA detection with no obvious influence on their efficiency. The results of our study demonstrated the potential application of this platform for the quantitative detection of ctDNA and the individualized analysis of cancer patients.

Electrochemical aptasensor based on electrodeposited poly(3,4-ethylenedioxythiophene)-graphene oxide coupled with Au@Pt nanocrystals for the detection of 17ß-estradiol.

An electrochemical aptasensor is reported for the sensitive and specific monitoring of 17ß-estradiol (E2) based on the modification of electrodeposited poly(3,4-ethylenedioxythiophene) (PEDOT)-graphene oxide (GO) coupled with Au@Pt nanocrystals (Au@Pt). With excellent conductivity, chemical stability and active sites, the PEDOT-GO nanocomposite film was firstly in situ polymerized on the glassy carbon electrode by cyclic voltammetry. Subsequently, one-step synthesized Au@Pt were decorated on the conductive polymer, providing a platform for immobilizing the aptamer and enhancing the detecting sensitivity. With the addition of E2, since the interfacial electron transfer process was retarded by the E2-aptamer complex, the differential pulse voltammetry signal decreased gradually. Under optimum conditions, the calibration curve of E2 exhibited a linear range between 0.1 pM and 1 nM, with a low detection limit (S/N = 3) of 0.08 pM. The developed aptasensor showed admiring selectivity, stability, and reproducibility. It was tested in human serum, lake water and tap water samples after low-cost and simple pretreatment. Consequently, the developed platform could provide a new design thought for ultrasensitive detection of E2 in clinical and environmental samples.

Graphene oxide-based composite organohydrogels with high strength and low temperature resistance for strain sensors.

In recent years, a rapid development of polymeric hydrogel-based sensors has been witnessed. However, conventional hydrogels often exhibit poor mechanical properties. Additionally, the use of these sensors at temperatures <0 °C is limited due to the freezing of the water molecules in the hydrogel matrix. In this study, graphene oxide/poly(acrylamide-co-N-(3-amino propyl)methacrylamide) [poly(AAm-co-APMA)/GO] hydrogels have been synthesized by UV photo-initiation polymerization. Subsequently, the poly(AAm-co-APMA)/GO-Gly (PAAG-Gly) organohydrogels were obtained by glycerol replacement. GO and glycerol had multiple interactions with the polymer chains, which endowed the physically crosslinked organohydrogel with a high fracture stress of up to 782.9 ± 38.6 kPa. Also, the glycerol molecules formed hydrogen bonds with the water molecules, thus inhibiting the formation of ice crystals. After storage at -20 °C for 24 h, the PAAG-Gly organohydrogels retained their superior mechanical properties, adhesion strength, and electrical conductivity. Once the cut surfaces of the organohydrogel were contacted, the conductive path was rapidly self-healed. Moreover, the PAAG-Gly organohydrogels exhibited excellent cytocompatibility. At 100% strain, the gauge factor of the organohydrogel-based sensor reached 4.22. The organohydrogel-based sensor revealed the capability to monitor human motions, such as finger, wrist and knee movements.

Thionine-functionalized three-dimensional carbon nanomaterial-based aptasensor for analysis of Aß oligomers in serum.

How to sensitively detect early biomarkers of Alzheimer's disease (AD) is nowadays, one of the major challenges. In this work, Aß oligomers (AßO), one of the AD biomarkers, was analyzed using an electrochemical aptasensor, which was prepared based on thionine (Th) - functionalized three - dimensional carbon nanomaterials (reduced graphene oxide (rGO) and multi-wall carbon nanotubes (MWCNTs)) immobilized DNA-aptamer. Th, a positively charged planar aromatic molecule, form many π - π conjugated structures with rGO and MWCNTs, then improving the structural stability, electron transfer and the capacitive properties of Th-rGO-MWCNTs nanocomposites. Under the optimal conditions, differential pulse voltammetry (DPV) current responses decreased with the increase of AßO concentration. The obtained AßO aptasensor presented a wide linear range of 0.0443 pM-443.00 pM and limit of detection (LOD) was 10 fM. Meanwhile, AßO aptasensor displayed remarkable stability and selectivity. It has a great potential for early diagnosis of AD in human real serum samples.

An ultrasensitive aptamer-antibody sandwich cortisol sensor for the noninvasive monitoring of stress state.

Cortisol is a major glucocorticoid that can affect physiological activities in the human body. Besides, it is also a biomarker that can reflect the stress state of the body. Therefore, in order to monitor stress states in a sensitive and non-invasive manner, an ultra-sensitive aptamer-antibody sandwich sensor modified with multi-walled carbon nanotubes, ordered mesoporous carbon CMK-3, and silver nanoparticles (MWCNTs/CMK-3/AgNPs) was proposed for non-invasive detection of cortisol in human saliva. The MWCNTs/CMK-3/AgNPs nanocomposite was fixed on the surface of the glassy carbon electrodes (GCEs) as the material for the first round of signal amplification, and secondary signal amplification was realized by conjugating cortisol antibodies with gold nanoparticles (AuNPs). Finally, the aptamer-antibody sandwich pattern was used to specifically recognize and bind cortisol. The concentration response range for this aptamer-antibody sandwich sensor is 0.1 pg/mL-10 ng/mL, and the limit of detection (LOD) is 0.09 pg/mL. So far, the LOD of this sensor has been relatively low, showing its good sensitivity, selectivity, stability, and reproducibility. Furthermore, it has been successfully applied to detect cortisol in saliva samples to compare the stress states of postgraduates and undergraduates.

Advancements in electrochemical biosensing for respiratory virus detection: A review.

Respiratory viruses are real menace for human health which result in devastating epidemic disease. Consequently, it is in urgent need of identifying and quantifying virus with a rapid, sensitive and precise approach. The study of electrochemical biosensors for respiratory virus detection has become one of the most rapidly developing scientific fields. Recent developments in electrochemical biosensors concerning respiratory virus detection are comprehensively reviewed in this paper. This review is structured along common detecting objects of respiratory viruses, electrochemical biosensors, electrochemical biosensors for respiratory virus detection and future challenges. The electrochemical biosensors for respiratory virus detection are introduced, including nucleic acids-based, immunosensors and other affinity biosensors. Lastly, for Coronavirus disease 2019 (COVID-19) diagnosis, the future challenges regarding developing electrochemical biosensor-based Point-of-Care Tests (POCTs) are summarized. This review is expected to provide a helpful guide for the researchers entering this interdisciplinary field and developing more novel electrochemical biosensors for respiratory virus detection.

A novel SWCNT-amplified "signal-on" electrochemical aptasensor for the determination of trace level of bisphenol A in human serum and lake water.

A novel "signal-on" electrochemical aptasensor was developed for ultrasensitive and specific detection of BPA, using single-walled carbon nanotubes (SWCNT) as the electro-catalytic probe for further signal amplification. The multi-walled carbon nanotubes (MWCNT), amino-functionalized magnetite, and gold nanoparticles (NH2-Fe3O4/Au NPs) were applied first to modify the glassy carbon electrode (GCE) surface and to form a nanomaterial film with satisfactory conductive properties, stability, and biocompatibility. The BPA aptamer was then loaded onto the sensing platform by hybridization with complementary DNA (CDNA). In the presence of BPA it combines with the aptamer and the BPA-aptamer conjugate was released from the electrode;subsequently the added SWCNT and CDNA assembled quickly. Thus, the dual-amplification of the "signal-on" electrochemical aptasensor takes effect. The [Fe (CN)6]3-/4- redox probe signal (∆I) detected by DPV (differential pulse voltammetry) is proportional to the negative logarithm of BPA concentration between 10-19 M and 10-14 M. The detection limit is 0.08 aM. Importantly, the proposed biosensor represents a successful application for determination of BPA in human serum and lake water. Schematic representation of SWCNT-amplified "signal-on" electrochemical aptasensor for the detection of trace level of bisphenol A in human serum and lake water.

Signal multi-amplified electrochemical biosensor for voltammetric determination of tau-441 protein in biological samples using carbon nanomaterials and gold nanoparticles to hint dementia.

A signal multi-amplified electrochemical biosensor was fabricated for tau-441 protein, a dementia biomarker. It utilizes a carbon nanocomposite film modified gold electrode. The carbon nanocomposite film was composed of multi-walled carbon nanotubes (MWCNTs), reduced graphene oxide (rGO), and chitosan (CS). For the nanocomposite film, rGO improved the dispersibility of MWCNTs, and the effective surface area of MWCNTs was increased. On the other hand, MWCNTs also increased the interlayer spacing of rGO, resulting in a thinner rGO layer. MWCNTs-rGO had a better conductivity than that of MWCNTs and rGO due to the synergy effect. Biocompatible CS was employed for immobilization of the specific antibody. Tau-441 protein was modified with gold nanoparticles (AuNPs) for signal amplification again. The response of the electrochemical biosensor is linear in the range 0.5-80 fM (0.5, 1.5, 5, 10, 40, 80 fM) with a limit of detection (LOD) of 0.46 fM, using differential pulse voltammetry (DPV) in a potential range of - 100-500 mV. The biosensor was successfully applied to the analysis of serum samples of 14 normal people, 14 mild cognitive impairment (MCI) patients, and 14 dementia patients. Graphical abstract Schematic representation of signal multi-amplified electrochemical biosensor for determination of tau-441 protein in human serum.

Intraventricular fibrinolytic for the treatment of intraventricular hemorrhage: a network meta-analysis.

OBJECTIVE: To explore which intraventricular fibrinolytic agent - urokinase (UK) or recombinant tissue plasminogen activator (rt-PA) - combined with extraventricular drainage (EVD) is most suitable for patients with spontaneous intraventricular hemorrhage (IVH). PATIENTS AND METHODS: We searched PubMed, MEDLINE, OVID, Embase, and Cochrane Library databases for relevant articles and assessed their quality and extracted statistical analyses using Stata 13.0 and Revman 5.3 software. RESULTS: Compared with EVD alone, EVD combined with an agent causing intraventricular fibrinolysis (IVF) improved the survival and prognosis of patients with IVH. Regarding the patients' survival rates and prognoses, the treatments, from best to worst results were EVD + UK, EVD + rt-PA, EVD alone. The proportion of patients with serious disability also increased with these treatments, however, with the highest to lowest proportions being EVD + rt-PA, EVD + UK, EVD alone. In addition, EVD + IVF was associated with a higher risk of intracranial rebleeding (from lowest to highest incidence: EVD alone, EVD + rt-PA, EVD + UK). Finally, EVD + UK is associated with an increased risk of potential intracranial infection (from lowest to highest incidence: EVD + rt-PA, EVD alone, EVD + UK). CONCLUSIONS: EVD + UK may be the best approach to improving patients' survival rate and prognosis. However, it also presents the highest risk of intracranial infection and rebleeding. EVD + IVF increased the proportion of patients with serious disability.

New trends in the electrochemical detection of endocrine disruptors in complex media.

Endocrine disruptors (EDCs) are substances existing in the environment which affect animal and human endocrine functions and cause diseases. A small quantity of EDCs can have a serious impact on the body. Currently, enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), and other traditional methods are used to detect EDCs. Although their sensitivity and reliability are good, these methods are complex, expensive, and not feasible to use in the field. Electrochemical techniques present good potential for the detection of EDCs owing to their low cost, simple, and wearable instrumentation. This paper presents the new trends in this field over the last 3 years. Some simple materials can allow some EDCs to be directly detected. New designs of biosensors, such as aptasensors, allow a femtomolar limit of detection to be reached. Many types of nanomaterial-based sensors were tested; carbonaceous nanomaterials, such as multiwalled carbon nanotubes (MWCNTs) and reduced graphene oxide (rGO), associated or not with other types of nanoparticles were included in numerous designs. Molecularly imprinted polymer (MIP)-based sensors constitute an emerging field. All the presented electrochemical sensors were successfully tested for the detection of EDCs in different types of real samples.