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Extracellular vesicles (EVs) are emerging as valuable biomarkers for liquid biopsy because they reflect the molecular composition of their originating cells and play a key role in intercellular communication. However, most EV-based analytical workflows rely on multistep isolation and chemical lysis procedures, which increase processing complexity, time, and contamination risks. Here, we introduce a simplified, isolation and reagent free, strategy for rapid quantification of EV-derived lung cancer biomarkers by electric field (EF)-mediated EV lysis method to directly break down EVs in serum, followed by label-free detection of lung cancer with non-faradaic electrochemical impedance spectroscopy (N-EIS). Systematic optimization of waveform shapes (sine, square, and sawtooth), frequencies (10 Hz to 100 kHz), and voltages (50 mV to 1 V) shows that a low-voltage (50 mV) square-wave signal at 1 kHz is optimal for EV electropermeabilization while maintaining encapsulated biomarkers. The efficacy of EF-induced EV lysis was validated by ELISA-based quantification of EV-derived lung cancer-associated proteins. The proposed workflow eliminates the need for labor-intensive isolation and chemical reagents, achieving a detection time of 30 min. The proposed platform achieved high sensitivity (> 80%) on antibody functionalized screen-printed gold electrode, with limit of detection of 0.28 pg mL(-)& sup1; (TSG101), 0.56 pg mL(-)& sup1; (GM2AP), 7.38 pg mL(-)& sup1; (MUC1) and 0.42 pg mL(-)& sup1; (EGFR). Clinical evaluation using human serum successfully discriminated between healthy individuals and lung cancer patients with high statistical confidence. These results highlight the potential of EF-assisted N-EIS as a robust liquid biopsy tool, offering a scalable pathway toward portable diagnostic systems for decentralized oncological screening and non-invasive monitoring of early-stage disease.
We introduce the EV-Disrupt and Detect System (EDDS), an innovative, portable biosensor utilizing electrochemical impedance spectroscopy (EIS) for the swift, low-volume, and economical assessment of extracellular vesicle (EVs)-related lung cancer biomarkers. The EDDS combines electric field-induced EVs disruption with the simultaneous detection of 4 critical biomarkers: TSG101, EGFR, GPC1, and GM2AP, directly from serum. EVs disruption occurred within 30 seconds utilizing a 50 mV, 1 kHz square wave, with disruption efficiency validated by nanoparticle tracking analysis (93.9%) and Western blotting to ensure protein integrity. Post-disruption, the released cargo was quantified by electrochemical impedance spectroscopy (EIS) across 4 specialized screen-printed electrodes (SPEs), with results corroborated by enzyme-linked immunosorbent test (ELISA). The electric field parameters (voltage, frequency, and duration) were optimized with $150~\mu $ L of serum, yielding a 0.218-2.809-fold enhancement in detectable biomarker concentrations. The EDDS markedly decreases processing time, cost, and technological complexity by obviating the necessity for traditional EVs isolation techniques such as ultracentrifugation or chromatography. This integrated platform facilitates direct EVs disruption and multiplexed biomarker identification within a singular workflow, providing a robust instrument for minimally invasive cancer diagnostics and advancing broader clinical applications in liquid biopsy.
ABSTRACT Cataracts have reportedly been linked to radiation exposure. The goal of this study was to investigate the relationship between natural gamma-radiation exposure and the prevalence of cataracts among female inhabitants of Karunagappally, Kerala, India’s high natural background radiation areas (HNBRA). From 2013 to 2014, a total of 840 women, whose lifetime natural radiation exposure had been estimated, underwent ophthalmic examinations and structured interviews. Five hundred and fifty women were from the control region (low- and medium dose areas), and 290 were from high natural background radiation area. The Lens Opacities Classification System was applied for grading cataracts. In the control region, 79 (14%) cortical, 10 (2%) posterior subcapsular and 24 (4%) nuclear cataracts were identified, whereas 54 (19%), 9 (3%) and 10 (4%) cases, respectively, were observed in high natural background radiation area. Cortical cataracts were significantly associated with cumulative radiation doses of 200 mGy or greater (odds ratio: 2.46; 95% confidence interval: 1.11–5.45) in logistic regression models adjusted for age, body mass index and family history of diabetes mellitus. After combining cortical and posterior subcapsular cataracts—subtypes more closely connected to radiation exposure—women exposed to more than 140 mGy in their lifetime, a reported threshold, exhibited a significantly increased risk (odds ratio: 1.25; 95% confidence interval: 1.00–1.56). The present study found a significant association between cortical and posterior subcapsular cataract prevalence and high natural background radiation exposure.
1582 Background: Lung cancer is the leading cause of cancer related mortality worldwide with Non small lung cancer (NSCLC) constituting the majority of cases. EGFR mutations, predominantly exon 19 and Exon 21 L858R are actionable targets in approximately 25-30% Indian patients. Third generation EGFR tyrosine kinase inhibitors have set new benchmarks in the treatment of metastatic EGFR mutation positive NSCLC. However real world adoption in India faces significant barriers including financial constraints and healthcare disparities. Methods: Our objective was to evaluate whether patients with EGFR mutation positive metastatic NSCLC receiving the standard of care treatment and analyze demographic, clinical and molecular characteristics of EGFR mutation positive lung cancer patients treated at our center and compare treatment patterns and survival outcomes with national and global data. This retrospective study analyzed 894 stage 4 NSCLC patients treated between 2018-2023 of these 252 (28.1%) were EGFR mutation positive. Data on EGFR types, treatment modalities and survival outcomes were collected and analyzed. Kaplan Meir survival analysis was performed to estimate progression free survival (PFS) and overall survival (OS). Results: First line Osimertinib was median OS was 30 months and PFS was 20 months. The standard of care at that time received by 13.5% only. Other TKI alone (Gefitinib, Erlotinib and Afatinib) median OS was 21 months while PFS was 12 months. Other TKI with chemotherapy median OS 27 months and PFS was 18 months. Mutation specific outcomes showed exon 19 deletions had better overall survival 27 months PFS 16 months compared to Exon 21 L858R (OS 16; PFS 11 months). T790M were identified in 71% patients progressing after first line treatment. Second line osimertinib achieved a median PFS of 9.5 months. Conclusions: Despite the efficacy of osimertinib demonstrated in global trials, its adoption was limited to 13.5% of eligible patients in this cohort due to economic barriers. These findings emphasize the urgent need for systemic interventions to improve access to advanced therapies in India. Policymakers and healthcare systems must address these gaps through measures like government subsidies, expanded insurance coverage and cost effective diagnostic platforms to ensure equitable access to precision oncology in resource limited settings.
