Combined SERS Microfluidic Chip with Gold Nanocone Array for Effective Early Lung Cancer Prognosis in Mice Model

Abstract

Introduction:As the most common malignant tumor in the world, the prognosis of patients with advanced lung cancer remains poor even after treatment. There are many prognostic marker assays available, but there is still more room for the development of highthroughput and sensitive detection of circulating tumor DNA (ctDNA). Surface-enhanced Raman spectroscopy (SERS), a spectroscopic detection method that has received wide attention in recent years, can achieve exponential amplification of Raman signals by using different metallic nanomaterials. Integrating SERS with signal amplification strategy into the microfluidic chip and applying it to ctDNA detection is expected to be an effective tool for the prognosis of lung cancer treatment effect in the future. Methods: To construct a high-throughput SERS microfluidic chip integrated with enzyme-assisted signal amplification (EASA) and catalytic hairpin self-assembly (CHA) signal amplification strategies, using hpDNA-functionalized Au nanocone arrays (AuNCAs) as capture substrates and cisplatin-treated lung cancer mice to simulate the detection environment for sensitive detection of ctDNA in serum of lung cancer patients after treatment. Results:The SERS microfluidic chip constructed by this scheme, with two reaction zones, can simultaneously and sensitively detect the concentrations of four prognostic ctDNAs in the serum of three lung cancer patients with a limit of detection (LOD) as low as the aM level. The results of the ELISA assay are consistent with this scheme, and its accuracy is guaranteed. Conclusion: This high-throughput SERS microfluidic chip has high sensitivity and specificity in the detection of ctDNA. This could be a potential tool for prognostic assessment of lung cancer treatment efficacy in future clinical applications.

On-Chip Photonic Detection Techniques for Non-Invasive In Situ Characterizations at the Microfluidic Scale

“…With a detection limit at the single-molecule level, SERS is considered as an ultra-sensitive technique [ 79 , 80 ]. Importantly, SERS eliminates any interference from water and does not cause damage to samples, making it suitable for the analysis of biological samples [ 81 , 82 , 83 , 84 , 85 , 86 ] or cancer diagnostics [ 87 , 88 , 89 , 90 , 91 ]. Equally, microfluidic sensors based on SERS detection have been proposed for very diverse applications, ranging from the diagnosis of Alzheimer’s disease [ 92 ] to the rapid analysis of food contaminants [ 93 ] or the high-throughput detection of explosives [ 94 ] or harmful substances [ 95 ].…”

SERS-based microdevices for use as in vitro diagnostic biosensors

“…Lung cancer is one of the most common cancers with high mortality rates worldwide. A significant challenge in managing lung cancer is obtaining an accurate diagnosis of cancerous lesions, which warrants the development of an efficient and sensitive method that can detect the 307 This chip exhibited excellent sensitivity and specificity in ctDNA detection, indicating its potential as a valuable tool for evaluating the effectiveness of lung cancer treatment in clinical settings. Gao et al proposed a 4 inch ultrasensitive SERS substrate for early lung cancer diagnosis 308 by harnessing the unique particle-incavity structure of the substrate, resulting in excellent SERS performance for the detection of gaseous malignancy biomarkers at an LoD of 0.1 ppb.…”

SERS biosensors for liquid biopsy towards cancer diagnosis by detection of various circulating biomarkers: current progress and perspectives

“…C Capture of ctNA requires even more efficient mixing, a serpentine channel creating Dean vortices provides such mixing capability which is followed by a further enhanced SERS signal using a plasmonic substrate. Reproduced with permission [ 131 ]. Copyright 2023, Dove Medical Press Limited.…”

“…and Cao et al . used this strategy to detect lung and gastric cancer ctDNAs at attomolar ranges [ 131 , 132 ]. Interestingly, the sample and SERS nanotags were driven into the microfluidic device chambers through comb-like hydrophilic channels that create capillary flow, thus achieving the passive flow of sample without the need for a pump.…”