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Sensitivity assay on the microchip platform. (a) Raman spectra for various concentration of MCSP protein spiked in PBS, 50 pg ml⁻¹ (grey), 100 pg ml⁻¹ (violet), 200 pg ml⁻¹ (orange), 500 pg ml⁻¹ (green), and 1000 pg ml⁻¹ (pink). (b) Corresponding bar graphs are showing the average Raman intensity for the various concentration of MCSP protein spiked in PBS. Each bar represents the average from three trials (n = 3) and error bars represent the standard deviation within each experiment
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The detection of circulating biomarkers in liquid biopsies has the potential to provide a non-invasive route for earlier cancer diagnosis and treatment management. Melanoma chondroitin sulfate proteoglycan (MCSP) is a membrane protein characteristic for melanoma cell migration and tissue invasion with its soluble form (sMCSP) serving as a potential...
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Chondroitin sulfate (CS) is a major component of the extracellular matrix found to be abnormally accumulated in several types of cancer tissues. Previous studies have indicated that CS synthases and modification enzymes are frequently elevated in human gliomas and are associated with poor prognosis. However, the underlying mechanisms of CS in cance...
Citations
... To perform SERS measurements, the targets are typically isolated/purified from the samples first and identified through SERS nanotags for signal readout. Experimentally, under the laser illumination with specific wavelength (e.g., 632.8 nm and 785 nm), the generated Raman spectra are recorded with either a portable Raman instrument in a cuvette or confocal Raman microscope using user-defined integration time [32,33]. ...
Precision cancer medicine necessitates a personalized treatment plan for each individual patient. Given cancer’s heterogeneity and dynamic nature, the plot of patient-specific signatures composed of multiple cancer circulating biomarkers is useful to reveal the complete tumor landscape for guiding precision medicine. As an emerging new technology, surface-enhanced Raman scattering (SERS) shows the intrinsic advantage of performing multiplexed detection with the extremely narrow Raman spectral line widths. In this review, we first discuss the design principle of SERS nanotags to enable the detection of multiple circulating biomarkers, highlighting the important roles of plasmonic nanostructures and triple bond-modulated Raman reporters. Following this, we detail the use of isotropic and anisotropic nanostructures as SERS enhancement substrates for amplifying Raman signals in multi-biomarker detection. Furthermore, we present the triple bond-modulated molecules as Raman reporters in SERS nanotags to expand the multiplexing capability for biomarker measurements. Finally, we offer critical insights into the challenges and perspectives of SERS nanotags for cancer diagnosis, particularly from the aspect of future clinical transition. It is expected that this review can facilitate the design of more functional SERS nanotags with high sensitivity and multiplexing capability to assist early and accurate cancer screening. We also believe our review will be of interest in the fields of molecular imaging, biomedicine, and analytical chemistry.
... In recent years, novel detection techniques such as fluorescence nanoparticle probes, nanostructured devices, and surface-enhanced Raman spectroscopy (SERS) have been developed [91,92]. ...
Microfluidics provides a precise synthesis of micro-/nanostructures for various applications, including bioengineering and medicine. In this review article, traditional and microfluidic synthesis methods of zinc oxide (ZnO) are compared concerning particle size distribution, morphology, applications, reaction parameters, used reagents, and microfluidic device materials. Challenges of traditional synthesis methods are reviewed in a manner where microfluidic approaches may overcome difficulties related to synthesis precision, bulk materials, and reproducibility.
Advances in surface-enhanced Raman scattering (SERS) detection have helped to overcome the limitations of traditional in vitro diagnostic methods, such as fluorescence and chemiluminescence, owing to its high sensitivity and multiplex detection capability. However, for the implementation of SERS detection technology in disease diagnosis, a SERS-based assay platform capable of analyzing clinical samples is essential. Moreover, infectious diseases like COVID-19 require the development of point-of-care (POC) diagnostic technologies that can rapidly and accurately determine infection status. As an effective assay platform, SERS-based bioassays utilize SERS nanotags labeled with protein or DNA receptors on Au or Ag nanoparticles, serving as highly sensitive optical probes. Additionally, a microdevice is necessary as an interface between the target biomolecules and SERS nanotags. This review aims to introduce various microdevices developed for SERS detection, available for POC diagnostics, including LFA strips, microfluidic chips, and microarray chips. Furthermore, the article presents research findings reported in the last 20 years for the SERS-based bioassay of various diseases, such as cancer, cardiovascular diseases, and infectious diseases. Finally, the prospects of SERS bioassays are discussed concerning the integration of SERS-based microdevices and portable Raman readers into POC systems, along with the utilization of artificial intelligence technology.
Tumor cells display heterogenous molecular signatures during the course of cancer and create distinct tumor cell subpopulations which challenge effective therapeutic decisions. Detection and monitoring of these heterogenous molecular events at single cell level are imperative to identify tumor cell subpopulations and to engage the best therapeutic options for the individual patient. Herein, a microfluidic liquid biopsy platform to analyze circulating tumor cells (CTCs) at single cell level is reported. The individual CTCs are captured in an alternating current‐induced microfluidic platform and analyzed by using surface‐enhanced Raman scattering spectroscopy. This platform selectively captures single CTCs from the patient's peripheral blood mononuclear cells. Using cell line models and patient samples, it is shown that the assay can simultaneously detect multiple protein biomarkers on a single CTC. The platform can stratify the CTCs into different subpopulations based on their cancer‐associated protein signature changes in response to drug treatment. This enables the identification of CTC subpopulations that are probably not responding to treatment and may assist clinicians in specifically monitoring and eliminating therapy‐resistant cancer cells within a lesion. This single CTC monitoring chip will likely have high clinical importance in disease diagnosis and treatment monitoring, and advance the knowledge of cancer heterogeneity.
Objective:
To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.
Methods:
The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.
Results:
GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).
Conclusion:
FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.
The methodological advancements in surface‐enhanced Raman scattering (SERS) technique with nanoscale materials based on noble metals, Au, Ag, and their bimetallic alloy Au–Ag, has enabled the highly efficient sensing of chemical and biological molecules at very low concentration values. By employing the innovative various type of Au, Ag nanoparticles and especially, high efficiency Au@Ag alloy nanomaterials as substrate in SERS based biosensors have revolutionized the detection of biological components including; proteins, antigens antibodies complex, circulating tumor cells, DNA, and RNA (miRNA), etc. This review is about SERS‐based Au/Ag bimetallic biosensors and their Raman enhanced activity by focusing on different factors related to them. The emphasis of this research is to describe the recent developments in this field and conceptual advancements behind them. Furthermore, in this article we apex the understanding of impact by variation in basic features like effects of size, shape varying lengths, thickness of core–shell and their influence of large‐scale magnitude and morphology. Moreover, the detailed information about recent biological applications based on these core–shell noble metals, importantly detection of receptor binding domain (RBD) protein of COVID‐19 is provided. Bimetallic alloy Au–Ag surface‐enhanced Raman scattering (SERS) biosensors exhibit ultrahigh SERS sensitivity. Au–Ag SERS‐based biosensors have been utilized in biological components detection, including; proteins, antigens antibodies complex, circulating tumor cells, DNA, and RNA (miRNA), etc.
The role of the extracellular matrix (ECM) remodeling in tumorigenesis and metastasis is becoming increasingly clear. Cancer development requires that tumor cells recruit a tumor microenvironment permissive for further tumor growth. This is a dynamic process that takes place by a cross-talk between tumor cells and ECM. As a consequence, molecules derived from the ECM changes associated to cancer are released into the bloodstream, representing potential biomarkers of tumor development. This article highlights the importance of developing and improving bioanalytical methods for the detection of ECM remodeling-derived components, as a step forward to translate the basic knowledge about cancer progression into the clinical practice.Graphical abstract
