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Machine learning algorithms enhance the specificity of cancer biomarker detection using SERS-based immunoassays in microfluidic chips
摘要： Specificity is a challenge in liquid biopsy and early diagnosis of various diseases. There are only a few biomarkers that have been approved for use in cancer diagnostics; however, these biomarkers suffer from a lack of high specificity. Moreover, determining the exact type of disorder for patients with positive liquid biopsy tests is difficult, especially when the aberrant expression of one single biomarker can be found in various other disorders. In this study, a SERS-based protein biomarker detection platform in a microfluidic chip and two machine learning algorithms (K-nearest neighbor and classification tree) are used to improve the reproducibility and specificity of the SERS-based liquid biopsy assay. Applying machine learning algorithms to the analysis of the expression level data of 5 protein biomarkers (CA19-9, HE4, MUC4, MMP7, and mesothelin) in pancreatic cancer patients, ovarian cancer patients, pancreatitis patients, and healthy individuals improves the chance of recognition for one specific disorder among the aforementioned diseases with overlapping protein biomarker changes. Our results demonstrate a convenient but highly specific approach for cancer diagnostics using serum samples.
关键词： cancer biomarkers,SERS,specificity,machine learning,microfluidic
更新于2025-09-19 17:15:36
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Bioplasmonic paper–based assay for perilipin-2 non-invasively detects renal cancer
摘要： Renal cell carcinoma (RCC) has poor survival prognosis because it is asymptomatic at an early, more curative stage. Recently, urine perilipin-2 (PLIN-2) was demonstrated to be a sensitive and speci?c biomarker for the noninvasive, early detection of RCC and an indispensable indicator to distinguish cancer from a benign renal mass. However, current Western blot or ELISA PLIN-2 assays are complicated, expensive, time-consuming or insensitive, making them unsuitable for routine analysis in clinical settings. Here we developed a plasmonic biosensor based on the high refractive index sensitivity of gold nanorattles for the rapid detection of PLIN-2 in patient urine. The paper-based plasmonic assay is highly sensitive and has a dynamic range of 50 pg/ml to 5 mg/ml PLIN-2. The assay is not compromised by variations in urine pH or high concentrations of interfering proteins such as albumin and hemoglobin, making it an excellent candidate for routine clinical applications. The urine PLIN-2 assay readily distinguished patients with pathologically proven clear cell carcinomas of various size, stage and grade (55.9 [39.5, 75.8] ng/ml, median [1st and 3rd quartile]) from age-matched controls (0.3 [0.3, 0.5] ng/ml), patients with bladder cancer (0.5 [0.4, 0.6] ng/ml) and patients with diabetic nephropathy (0.6 [0.4, 0.7] ng/ml). Urine PLIN-2 concentrations were roughly proportional to tumor size (Pearson coef?cient 0.59). Thus, this cost-effective and label-free method represents a novel approach to conduct a non-invasive population screen or rapid differential diagnosis of imaged renal masses, signi?cantly facilitating the early detection and diagnosis of RCC.
关键词： cancer biomarkers,cancer diagnostics,renal cancer,bioplasmonic assay
更新于2025-09-12 10:27:22
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Direct and Label-Free Detection of MicroRNA Cancer Biomarkers Using SERS-Based Plasmonic Coupling Interference (PCI) Nanoprobes
摘要： MicroRNAs (miRNAs), small non-coding endogenous RNA molecules, are emerging as promising biomarkers for early detection of various diseases and cancers. Practical screening tools and strategies to detect these small molecules are urgently needed in order to facilitate the translation of miRNA biomarkers into clinical practice. In this study, a label-free biosensing technique based on surface-enhanced Raman scattering (SERS), referred to as “plasmonic coupling interference (PCI)”, was applied for the multiplex detection of miRNA biomarkers. The sensing mechanism of the PCI technique relies on the formation of a nanonetwork consisting of nanoparticles with Raman labels located between adjacent nanoparticles that are interconnected by DNA duplexes. Due to the plasmonic coupling effect of adjacent nanoparticles in the nanonetwork, the Raman labels exhibit intense SERS signals. Such effect can be modulated by the addition of miRNA targets of interest that act as inhibitors to interfere with the formation of this nanonetwork, resulting in a diminished SERS signal. In this study, the PCI technique is theoretically analyzed and the multiplex capability for detection of multiple miRNA cancer biomarkers is demonstrated, establishing the great potential of PCI nanoprobes as a useful diagnostic tool for medical applications.
关键词： SERS,PCI,miRNAs,cancer biomarkers,MicroRNAs,plasmonic coupling interference,multiplex detection
更新于2025-09-12 10:27:22
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[IEEE 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) - Munich, Germany (2019.6.23-2019.6.27)] 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) - Anisotropic Fluorescence Emission at the Surface of 1D-Photonic Crystal Biochips
摘要： Novel disposable optical biochips based on one-dimensional photonic crystals (1DPC) sustaining Bloch surface waves (BSW) are a desirable tool for the detection of several disease-related biomarkers. In particular, cancer biomarkers have gained considerable attention, due to the increasing demand for cancer treatment. Within this framework, the herein proposed optical biochips can quantify low concentration (sub ng/mL) of the ERBB2 breast cancer biomarker in biological complex matrices. To discriminate ERBB2 levels in several different cell lysate samples, we made use of a biosensing platform based on 1DPC biochips and on a reading instrument that can work in both a label-free and a fluorescence detection mode. Such combined configuration provides the advantage of complementary information and lower limit of detection (LoD) in the fluorescence mode [1]. In the label-free configuration the BSW excitation is achieved by a prism coupling system (Kretschmann-Raether configuration), like in the surface plasmon resonance (SPR) technique, resulting in a dip in the angular reflectance spectrum, shifting its position due to the refractive index changes [2]. The fluorescence mode is carried out by making use of dye labeled antibodies bound at the 1DPC surface. Coupling between the dye labels and a BSW results in strongly directional fluorescence emission. The advantages brought by the 1DPC, when compared to metal structures, are smaller energy dissipation and narrower resonances [3]. Presently, there is no study about photobleaching in experiments with BSW sustained by 1DPC, while it is evident that such phenomenon cannot be neglected in biosensing assays carried out close to the LoD, where quantitative and accurate information is needed. Here we report for the first time on cancer detection assays carried out with our platform, in which the trustworthiness of the output is put in doubt by photobleaching, which not only affects the overall emission intensity but also its polarization distribution via the TE and TM BSW modes provided by the 1DPC. The experimental data is interpreted by means of a theoretical model for the orientational distribution of dye labels over time, taking into account the density of the optical states of the 1DPC, photobleaching and rotational diffusion of surface bound emitters. The approach permits to model anisotropic fluorescence emission and to manage photobleaching effects in biosensing assays, leading to their correct interpretation.
关键词： one-dimensional photonic crystals,optical biochips,Bloch surface waves,cancer biomarkers,fluorescence emission,photobleaching
更新于2025-09-12 10:27:22