Explore the vast range of titles available.

Numerous studies have shown that exosomes are closely related to the pathogenesis of various diseases, especially cancers. Therefore, a rapid and sensitive method for exosome detection will be of great importance for the diagnosis and prognosis of diseases. We report here a method for exosome detection based on the CD63 aptamer and clustered regular interspaced short palindromic repeats (CRISPR)/Cas12a system. This method consists mainly of exosomal membrane protein recognition based on the CD63 aptamer and signal amplification based on CRISPR/Cas12a. The CD63 aptamer, as an easily adaptable nucleic acid strand, is responsible for the conversion of the amounts of exosomes into nucleic acid detection, whereas CRISPR/Cas12a is responsible for highly specific nucleic acid signal amplification. The detection range of the method was determined as 3 × 103–6 × 107 particles per microliter. Additionally, we successfully applied this method to detect exosomes in clinical samples from both healthy individuals and patients with lung cancer, and the results were highly consistent with those obtained by nanoparticle tracking analysis. In general, this method provides a highly sensitive and specific method for the detection of exosomes and offers an avenue toward future exosome-based diagnosis of diseases.

Terahertz (THz=1012Hz) radiation has attracted wide attention for its unprecedented sensing ability and its noninvasive and nonionizing properties. Tremendous strides in THz instrumentation have prompted impressive breakthroughs in THz biomedical research. Here, we review the current state of THz spectroscopy and imaging in various biomedical applications ranging from biomolecules, including DNA/RNA, amino acids/peptides, proteins, and carbohydrates, to cells and tissues. We also address the potential biological effects of THz radiation during its biological applications and propose future prospects for this cutting-edge technology. THz spectroscopy has proven to be an innovative tool for providing new insights into the hydration shell in the solvation dynamics of protein solutions. THz in-line digital holography, THz near-field imaging modality, and THz endoscope prototypes have been utilized to identify abnormal tissues faster and more accurately. Increasing applications of artificial modeling and numerical computation are becoming essential supplements for THz biological effect studies.

The demand for advanced bacterial detection tools is continuously increasing, promoted by its significant benefits in various applications. For instance, in the medical field, these tools would facilitate decision making about more tailored therapies once the infection source has been identified. In the past few years, terahertz (THz = 10 12  Hz) spectroscopy has also shown potential as a novel bacterial detection modality due to its unique advantages. Impressive breakthroughs have been achieved in this field related to bacterial component characterization, spore identification, and cell detection. However, some intrinsic limitations and technical bottlenecks have led to some debates about the practicability of its clinical adoption. In this review, we summarize the progress achieved in this field and discuss some challenges and strategies for future implementation of practical applications.

The detection of tumor markers is very important in early cancer diagnosis; however, tumor markers are usually present at very low concentrations, especially in the early stages of tumor development. Surface plasmon resonance (SPR) is widely used to detect biomolecular interactions; it has inherent advantages of being high-throughput, real-time, and label-free technique. However, its sensitivity needs essential improvement for practical applications. In this study, we developed a signal amplification strategy using antibody-quantum dot (QD) conjugates for the sensitive and quantitative detection of α-fetoprotein (AFP), carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA 21-1) in clinical samples. The use of a dual signal amplification strategy using AuNP-antibody and antibody-QD conjugates increased the signal amplification by 50-folds. The constructed SPR biosensor showed a detection limit as low as 0.1 ng/mL for AFP, CEA, and CYFRA 21-1. Moreover, the results obtained using this SPR biosensor were consistent with those obtained using the electrochemiluminescence method. Thus, the constructed SPR biosensor provides a highly sensitive and specific approach for the detection of tumor markers. This SPR biosensor can be expected to be readily applied for the detection of other tumor markers and can offer a potentially powerful solution for tumor screening.

In this study, we fabricated a high-sensitivity “signal-off” electrochemical aptasensing platform for quantifying circulating tumor cells (CTCs) based on target-triggered signal readout of methylene blue (MB). Au nanoparticles (AuNPs) were introduced to enlarge the specific surface area of the gold electrode (GE), which would immobilize homogeneous and more MB-aptamers. MB-modified and stem-loop-like aptamers were assigned as a recognition element with K562 cells. Thiolated complementary strands hybridized with MB-aptamers to form double-stranded DNA (dsDNA) conformation which were further self-assembled on the surface of AuNP-modified GE, leading to a marked current peak of MB signal. In the presence of K562 cells, the MB-aptamers preferred to recognize and bind with the cells, causing the disassembly of MB-aptamers from the GE surface. Therefore, the reduced value of MB signal was related to the number of K562 cells. With the proposed aptasensor, a dynamic linear range from 1 × 102 to 1 × 106 cells mL−1 was obtained with a detection limit of 23 cells mL−1. Moreover, the aptasensor showed good selectivity, stability, and reproducibility as well as potential use in the clinical setting. Meanwhile, characterization techniques such as field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy were performed to analyze the evolution of the morphology and each fabricated step of the constructed aptasensor. Our proposed aptasensor could be designed as a universal platform for CTC determination by replacing tumor cell–specific aptamers, which is a promising strategy for basic research and clinical applications.

The article describes a SERS-based method for diagnosis of bacterial infections. Positively charged silver nanoparticles (AgNPs + ) were employed for identification of methicillin-resistant Staphylococcus aureus (MRSA). It is found that AgNPs + undergo self-assembly on the surface of bacteria via electrostatic aggregation. The assembled AgNPs + are excellent SERS substrates. To prove the capability of SERS to differentiate between S. aureus and other microorganisms, six standard strains including S. aureus 29213, S. aureus 25923, C. albicans , B. cereus , E. coli , and P. aeruginosa were tested. To further demonstrate its applicability for the identification of MRSA in clinical samples, 52 methicillin-sensitive S. aureus (MSSA) isolates and 215 MRSA isolates were detected by SERS. The total measurement time (include incubation) is 45 min when using a 3 μL sample. The method gives a strongly enhanced Raman signal (at 730 cm −1 and 1325 cm −1 ) with good reproducibility and repeatability. It was successfully applied to the discrimination of the six strain microorganisms. The typical Raman peaks of S. aureus at 730, 1154, 1325, and 1457 cm −1 were observed, which were assigned to the bacterial cell wall components (730 cm −1 - adenine, glycosidic ring mode, 1154 cm −1 - unsaturated fatty acid, 1325 cm −1 - adenine, polyadenine, and 1457 cm −1 for -COO- stretching). S. aureus was completely separated from other species by partial least squares discriminant analysis (PLS-DA). Moreover, 52 MSSA isolates and 215 MRSA isolates from clinical samples were identified by PLS-DA. The accuracy was almost 100% when compared to the standard broth microdilution method. A classification based on latent structure discriminant analysis provided spectral variability directly. Conceivably, the method offers a potent tool for the identification of bacteria and antibiotics resistance, and for studies on antibiotic-resistance in general. Graphical abstract Schematic of the surface-enhanced Raman scattering (SERS) measurements on Staphylococcus aureus ( S. aureus ) using positively charged silver nanoparticles (AgNPs + ). AgNPs + are adsorbed on the bacterial cell wall by electrostatic attraction. SERS spectra were analyzed by PLS-DA for the identification of Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus aureus (MSSA). MRSA isolates were divided into four groups, including R1, R2, R3, and R4. MSSA just includes group S.

In the original publication [...]

The sensitive and accurate detection of tumor cells is essential for successful cancer therapy and improving cancer survival rates. However, current tumor cell detection technologies have some limitations for clinical applications due to their complexity, low specificity, and high cost. Herein, we describe the design of a terahertz anti-resonance hollow core fiber (THz AR-HCF) biosensor that can be used for tumor cell detection. Through simulation and experimental comparisons, the low-loss property of the THz AR-HCF was verified, and the most suitable fiber out of multiple THz AR-HCFs was selected for biosensing applications. By measuring different cell numbers and different types of tumor cells, a good linear relationship between THz transmittance and the numbers of cells between 10 and 106 was found. Meanwhile, different types of tumor cells can be distinguished by comparing THz transmission spectra, indicating that the biosensor has high sensitivity and specificity for tumor cell detection. The biosensor only required a small amount of sample (as low as 100 μL), and it enables label-free and nondestructive quantitative detection. Our flow cytometry results showed that the cell viability was as high as 98.5 ± 0.26% after the whole assay process, and there was no statistically significant difference compared with the negative control. This study demonstrates that the proposed THz AR-HCF biosensor has great potential for the highly sensitive, label-free, and nondestructive detection of circulating tumor cells in clinical samples.

The high sensitivity and specificity of terahertz (THz) biosensing are both promising and challenging in DNA sample detection. This study produced and refined a flexible THz MM biosensor for ultrasensitive detection of HBV in clinical serum samples based on a gold magnetic nanoparticle-mediated rolling circle amplification (GMNPs@RCA) sandwich assay under isothermal conditions. Typically, solid-phase RCA reactions mediated by circular padlock probes (PLPs) are triggered under isothermal conditions in the presence of HBV DNA, resulting in long single-stranded DNA (ssDNA) with high fidelity and specificity. Then, the resultant ssDNA was conjugated with detection probes (DPs) immobilized on gold nanoparticles (DP@AuNPs) to form GMNPs-RCA-AuNPs sandwich complexes. The HBV DNA concentrations were quantified by introducing GMNPs-RCA-AuNPs complexes into the metasurface of a flexible THz metamaterial-based biosensor chip and resulting in a red shift of the resonance peak of the THz metamaterials. This biosensor can lead to highly specific and sensitive detection with one-base mismatch discrimination and a limit of detection (LOD) down to 1.27E + 02 IU/ml of HBV DNA from clinical serum samples. The HBV DNA concentration was linearly correlated with the frequency shift of the THz metamaterials within the range of 1.27E + 02∼1.27E + 07 IU/ml, illustrating the applicability and accuracy of our assay in real clinical samples. This strategy constitutes a promising THz sensing method to identify virus DNA. In the future, it is hoped it can assist with pathogen identification and clinical diagnosis.

Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver disease, which markedly increases mortality. Pulmonary vascular remodelling (PVR) induced by circulating mediators plays an important role in the pathogenesis of HPS, while the underlying mechanism remains undefined. In the present study, we reported that endothelin-1 (ET-1) is up-regulated and annexin A1(ANXA1) is down-regulated in HPS rat, and ET-1 decreases the ANXA1 expression in a dose-dependent manner in rat pulmonary arterial smooth muscle cells (PASMCs). Then, we showed that ANXA1 can decrease nuclear p-ERK1/2 accumulation and decrease the cyclin D1 expression, thus resulting in the subsequent inhibition of PASMCs proliferation. As previously reported, we confirmed that ET-1 decreases the ANXA1 protein levels by the carbonylation and degradation of ANXA1. In conclusion, our research links the signaling cascade of ET1-ANXA1-cell proliferation to a potential therapeutic strategy for blocking IPS-associated PVR.