Epithelial–mesenchymal transition (EMT) is a primary mechanism for cancer metastasis. Detecting the activation of EMT can potentially convey signs of metastasis to guide treatment management and ...improve patient survival. One of the classic signatures of EMT is characterized by dynamic changes in cellular expression levels of E‐cadherin and N‐cadherin, whose soluble active fragments have recently been reported to be biomarkers for cancer diagnosis and prognosis. Herein, a microfluidic immunoassay (termed “SERS immunoassay”) based on sensitive and simultaneous detection of soluble E‐cadherin (sE‐cadherin) and soluble N‐cadherin (sN‐cadherin) for EMT monitoring in patients' plasma is presented. The SERS immunoassay integrates in situ nanomixing and surface‐enhanced Raman scattering readout to enable accurate detection of sE‐cadherin and sN‐cadherin from as low as 10 cells mL−1. This assay enables tracking of a concurrent decrease in sE‐cadherin and increase in sN‐cadherin in breast cancer cells undergoing drug‐induced mesenchymal transformation. The clinical potential of the SERS immunoassay is further demonstrated by successful detection of sE‐cadherin and sN‐cadherin in metastatic stage IV breast cancer patient plasma samples. The SERS immunoassay can potentially sense the activation of EMT to provide early indications of cancer invasions or metastasis.
An SERS immunoassay is presented for sensitive and simultaneous detection of the cadherin switch (E/N‐cadherin) in TGF‐β induced epithelial–mesenchymal transition (EMT) in vitro model. The assay is evaluated on stage IV breast cancer patients. The SERS immunoassay might have potential for monitoring EMT activities and early identification of individuals at risk of cancer metastasis.
Monitoring soluble immune checkpoints in circulating fluids has the potential for minimally-invasive diagnostics and personalised therapy in precision medicine. Yet, the sensitive detection of ...multiple immune checkpoints from small volumes of liquid biopsy samples is challenging. In this study, we develop a multiplexed immune checkpoint biosensor (MICB) for parallel detection of soluble immune checkpoints PD-1, PD-L1, and LAG-3. MICB integrates a microfluidic sandwich immunoassay using engineered single chain variable fragments and alternating current electrohydrodynamic in situ nanofluidic mixing for promoting biosensor-target interaction and reducing non-specific non-target binding. MICB provides advantages of simultaneous analysis of up to 28 samples in <2 h, requires as little as a single sample drop (i.e., 20 μL) per target immune checkpoint, and applies high-affinity yeast cell-derived single chain variable fragments as a cost-effective alternative to monoclonal antibodies. We investigate the assay performance of MICB and demonstrate its capability for accurate immune checkpoint detection in simulated patient serum samples at clinically-relevant levels. MICB provides a dynamic range of 5 to 200 pg mL-1 for PD-1 and PD-L1, and 50 to 1000 pg mL-1 for LAG-3 with a coefficient of variation <13.8%. Sensitive immune checkpoint detection was achieved with limits of detection values of 5 pg mL-1 for PD-1, 5 pg mL-1 for PD-L1, and 50 pg mL-1 for LAG-3. The multiplexing capability, sensitivity, and relative assay simplicity of MICB make it capable of serving as a bioanalytical tool for immune checkpoint therapy monitoring.
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 promising diagnostic surrogate. However, at the initial disease stage, the detection of sMCSP is challenging because of its low abundance and the required high specificity to analyze sMCSP in complex bodily fluids. Herein, we report a highly sensitive and high-throughput microchip that enables Surface Enhanced Raman Spectroscopy (SERS) immunoassay for parallel detection of up to 28 samples. Key to assay speed and sensitivity is the stimulation of an alternating current-induced nanofluidic mixing that improves target-sensor collision and displacement of non-specific molecules. Anisotropic Au-Ag alloy nanoboxes (NB's) with strong plasmonic hot spots provide single SERS particle sensitivity that enables ultrasensitive sMCSP detection of as low as 0.79 pM (200 pg ml
−1
). As a proof of concept study, we investigate the assay performance in simulated melanoma patient samples.
The detection of circulating biomarkers in liquid biopsies has the potential to provide a non-invasive route for earlier cancer diagnosis and treatment management.
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.
The single circulating tumor cell analysis platform specifically captures and identifies multiple target biomarkers on the cell surface by a surface‐enhanced Raman scattering microfluidic system. By analysing the heterogeneous expression patterns of individual cells, this platform enables the identification of a specific subpopulation of cells with higher biomarker expression during treatment with potential for informed therapeutic decision making.
Phosphorylation is a post-translational modification in proteins that changes protein conformation and activity for regulating signal transduction pathways. This mechanism is frequently impaired in ...lung cancer, resulting in permanently active constitutive phosphorylation to initiate tumor growth and/or reactivate pathways in response to therapy. We developed a multiplexed phosphoprotein analyzer chip (MPAC) that enables rapid (detection time: 5 min) and sensitive (LOD: 2 pg/μL) detection of protein phosphorylation and presents phosphoproteomic profiling of major phosphorylation pathways in lung cancer. We monitored phosphorylated receptors and downstream proteins involved in mitogen-activated protein kinase (MAPK) and PI3K/AKT/mTOR pathways in lung cancer cell line models and patient-derived extracellular vesicles (EV). Using kinase inhibitor drugs in cell line models, we found that the drug can inhibit the phosphorylation and/or activation of the kinase pathway. We then generated a phosphorylation heatmap by EV phosphoproteomic profiling of plasma samples isolated from 36 lung cancer patients and 8 noncancer individuals. The heatmap showed a clear difference between the noncancer and cancer samples and identify the specific proteins that are activated in the cancer samples. Our data also showed that MPAC could monitor immunotherapy responses by assessment of the phosphorylation states of the proteins, particularly for PD-L1. Finally, with a longitudinal study, we found that the phosphorylation levels of the proteins were indicative of a positive response to therapy. We believe that this study will lead to personalized treatment by providing a better understanding of the active and resistant pathways and will provide a tool for selecting combined and targeted therapies for precision medicine.
Liquid biopsy-based diagnosis in precision oncology exhibits significant advantages over the traditional tissue biopsies by offering dynamic assessment of tumour heterogeneity, minimally invasive ...procedures for frequent sampling, and cost-effective tests. Implementation of liquid biopsy-based diagnosis for precision oncology could be the key to provide a confident cancer screening with tailored risk assessment, patient stratification, and real-time monitoring of cancer therapies. To achieve precision oncology with liquid biopsy, the simultaneous analysis of multiple circulating tumour biomarkers is a powerful strategy to establish an accurate signature for each individual patient. Among various developed approaches for tumour biomarker detection, microfluidic devices integrated with surface enhanced Raman scattering (SERS) are emerging as one of the powerful techniques to support precision oncology based on its potential to provide multiplexing and high sensitivity. Particularly, the microfluidic devices provide miniaturised channels for parallel reactions and SERS has the extremely narrow spectra for intrinsic multiplexing. This mini review will focus on recently reported SERS microfluidic techniques, which are capable of simultaneous detection of multiple cancer biomarkers in liquid biopsy and have the promise to be integrated into precision oncology.
Liquid biopsy-based diagnosis in precision oncology exhibits significant advantages over the traditional tissue biopsies by offering dynamic assessment of tumour heterogeneity, minimally invasive procedures for frequent sampling, and cost-effective tests.
Introduction: Nomophobia is the fear of being away from mobile phone contact or in other words nomophobia is the irrational fear of being without mobile phone. Nomophobia is an emerging psychological ...public health problem. Aim: To determine the prevalence of nomophobia and pattern of mobile phone usage among medical students in Chennai. Materials and Methods: This cross-sectional study was done among 400 undergraduate medical students of Tagore Medical College and Hospital, Chennai, Tamil Nadu, India, studying from 1st year to 4th year, over a period of two months (July 2019 and August 2019). A structured questionnaire, developed by Yildirim C and Correia AP, was used to determine the prevalence of nomophobia among the study population. Stratified simple random sampling technique was used, where 100 students from each study year were selected. Descriptive statistics and chi-square test were done to compare the severity of nomophobia with various variables. Results: Out of 400 students, 50% (200) were males and 50% (200) were female students. Overall, 85% (340) used mobile internet. The top three reasons for using mobile internet were WhatsApp (95%), YouTube (81.3%) and Instagram (74.3%). The overall prevalence of nomophobia was 99% (396); 17.5% (70) showed severe nomophobia, 56.3% (225) moderate nomophobia, and 25.3% (101) had mild nomophobia. Severe nomophobia was associated with mobile usage >5 hours in a day (p-value=0.013). Conclusion: Health education and health awareness campaigns regarding nomophobia should be created among the undergraduate medical students.
Background: Medical education is recognized as a stressful education that often negatively impacts academic performance, physical health, and psychological health.
Aims and Objectives: Hence, the ...aims and objectives of this study was to assess the prevalence of depression, anxiety, and stress levels among undergraduate medical students.
Materials and Methods: A cross-sectional study was conducted at tertiary medical college in Kancheepuram from November 1, 2019, to December 31, 2019. A total of 360 undergraduate medical students were recruited from the 1st year to the final year. Each year was considered a stratum, and from each stratum through simple random sampling, 90 students were selected. A self-administered, pre-designed, pre-tested anonymous questionnaire-depression anxiety and stress scale 21 was used for data collection. CoGuide software was used for statistical analysis.
Results: Out of 360 medical students, 157 were male and 203 were female with a mean age of 19.98±1.17. Sixty-six (18.33%) study participants had a family history of mental illness. The overall prevalence of depression was 48.33%, 60.56% had anxiety, and 27.22% had stress. Females were more affected than their male counterparts. The prevalence was significantly more among those having a family history of mental illness.
Conclusion: The prevalence of depression was 48.33%, anxiety was 60.56%, and stress was 27.22%. Regular health education, stress counseling, and peer group sessions can reduce the level of mental distress among medical students.
The solid polymer electrolyte film is prepared using polyvinyl alcohol and alum by the reactive blending method. Different wt% of alum is used for the preparation of the films. Temperature dependent ...properties of the films were characterized by IR, A/C conductivity, dielectric, conductance, DSC and TGA. The X-ray diffraction pattern of the synthesized film showed an increased crystallinity over pure PVA. The constituent present in the polymer film is found out by EDX measurement. The spin state in which metals present in the film is found out by XPS analysis. The thermal stability of the film is increased over pure PVA. The tensile curve of the polymer sample contains 0.15 wt% of alum showed a strain induced crystallisation behavior due to plasticizing effect of the embedded salt. The polymer sample contains 0.15 wt% of alum showed conductivity (AC) of 1.73 × 10
−4
S cm
−1
. Conduction pattern is studied by dielectric loss experiments.
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