Detection of Human Leukocyte Antigen Biomarkers in Breast Cancer Utilizing Label-free Biosensor Technology

According to the American Cancer Society, more than 200,000 women will be diagnosed with invasive breast cancer each year and approximately 40,000 will die from the disease. The human leukocyte antigen (HLA) class I samples peptides derived from proteasomal degradation of cellular proteins and presents these fragments on the cell surface for interrogation by circulating cytotoxic T lymphocytes (CTL). Generation of T-cell receptor mimic (TCRm) monoclonal antibodies (mAbs) which recognize breast cancer specific peptide/HLA-A*02:01 complexes such as those derived from macrophage migration inhibitory factor (MIF_19-27) and NY-ESO-1_157-165 enable detection and destruction of breast cancer cells in the absence of an effective anti-tumor CTL response. Intact class I HLA/peptide complexes are shed by breast cancer cells and represent potentially relevant cancer biomarkers. In this work, a breakthrough biomarker screening system for cancer diagnostics incorporating T-cell receptor mimic monoclonal antibodies combined with a novel, label-free biosensor utilizing guided-mode resonance (GMR) sensor technology is presented. Detection of shed MIF/HLA-A*02:01 complexes in MDA-MB-231 cell supernatants, spiked human serum, and patient plasma is demonstrated. The impact of this work could revolutionize personalized medicine through development of companion disease diagnostics for targeted immunotherapies.     

Application of a Plasmonic Biosensor for Detection of Human-Liver Tissues

A recently published plasmonic biosensor based on birefringent solid-core microstructured optical fiber is applied for detection of five types of human-liver tissues (normal N, metastatic MET, non-cancerous metastatic (NMET), hepatocellular carcinoma (HCC), and non-cancerous hepatocellular carcinoma (NHCC)). The birefringent behavior is obtained by removing five central air holes of a two-ring hexagonal lattice of holes in a gold covered silica fiber with the liver layer surrounding the fiber. The loss spectra show two resonant peaks corresponding to the phase matching points. To distinguish between normal and malignant liver tissues, we compare the relevant parameter for the type I and II core modes. Thus, for a decrease of the real part of the refractive index from 1.373431 (human-liver N) to 1.354602 (human-liver MET), the resonance spectral width δλ _0.5 is increased from 44.3 to 54.2 nm for the core mode II. In addition, the amplitude sensitivity S _A is decreased from 158.6 to 88.4 RIU⁻¹ for the same core mode. The advantages of another recently proposed plasmonic sensor based on a Bragg fiber are the larger values of the transmission loss, maximum value of the amplitude sensitivity, figure of merit, power fraction in a normal liver layer, and power fraction in the gold layer as compared with that for a microstructured fiber when applied for detection of a normal liver tissue. Another advantage of the Bragg fiber is related to the smaller value of the difference between maximal amplitude sensitivity and resonant wavelengths.

     

Application of a Plasmonic Biosensor for Detection of Human Blood Groups

A recently published plasmonic biosensor based on birefringent solid-core microstructured optical fiber is applied for the detection of human blood groups. The birefringent behavior is obtained by removing five central air holes of a two-ring hexagonal lattice of holes in a gold-covered silica fiber with the blood layer surrounding the fiber. The sensing performance of two resonant modes (I based on a phase matching point and II based on a loss matching point) are analyzed. For an increase of the refractive index from 1.3768 (human blood group A) to 1.3796 (human blood group O), the resonance spectral width δλ _0.5 is decreased from 26.8 to 25.8 nm for the core mode I and δλ _0.5 is increased from 28.3 to 33.2 nm for the core mode II. In addition, the amplitude sensitivity S _A is increased from 329.7 to 372.2 RIU^?1 for the core mode I and S _A is decreased from 298.2 to 283.7 RIU^?1 for the core mode II. The average value (26.20 nm for core mode I and 31.07 nm for core mode II) of δλ _0.5 from the human blood groups A, B, and O for our plasmonic biosensor is smaller in comparison with a recently published average value (39.10 nm) of the full width at half maximum (FWHM). Our biosensor can be calibrated for a glycerol-water solution by using the linear dependence between the refractive index n _a and the mass fraction w of the solutes.     

Plasmonic Biosensor Controlled by DNAzyme for On‐Site Genetic Detection of Pathogens

On‐site predetection of pathogens could significantly decrease of a disease outbreak or national loss in most of the countries. However, conventional detection techniques are limited in use for on‐site detection due to the necessity of specialized skill or equipment. Therefore, it is necessary to develop a new technique that can predetect pathogens in the field without special skills or equipment. Here, a DNAzyme strategy to control a plasmonic biosensor for rapid and simple visual detection of Salmonella choleraesuis is adopted. Multicomponent DNAzyme formed by target addition can cleave the linker effectively at 50 °C. Linker cleavage induces dispersion of two DNA‐immobilized gold nanoparticles and color change. Under optimized assay conditions, the target could be detected via visual discrimination sensitively and specifically. Moreover, the biosensor shows the possibility of practical use with contaminants and a 16S rRNA real target. As a result, the proposed plasmonic biosensor can visually detect S. choleraesuis without unstable enzymes, a specialized technique, or equipment. Therefore, these advantages could allow that this biosensor would be used for on‐site predetection to lower the risk of transmission of infectious diseases.     

Microfluidic Endothelium for Studying the Intravascular Adhesion of Metastatic Breast Cancer Cells

Background

The ability to properly model intravascular steps in metastasis is essential in identifying key physical, cellular, and molecular determinants that can be targeted therapeutically to prevent metastatic disease. Research on the vascular microenvironment has been hindered by challenges in studying this compartment in metastasis under conditions that reproduce in vivo physiology while allowing facile experimental manipulation.

Methodology/Principal Findings

We present a microfluidic vasculature system to model interactions between circulating breast cancer cells with microvascular endothelium at potential sites of metastasis. The microfluidic vasculature produces spatially-restricted stimulation from the basal side of the endothelium that models both organ-specific localization and polarization of chemokines and many other signaling molecules under variable flow conditions. We used this microfluidic system to produce site-specific stimulation of microvascular endothelium with CXCL12, a chemokine strongly implicated in metastasis.

Conclusions/Significance

When added from the basal side, CXCL12 acts through receptor CXCR4 on endothelium to promote adhesion of circulating breast cancer cells, independent of CXCL12 receptors CXCR4 or CXCR7 on tumor cells. These studies suggest that targeting CXCL12-CXCR4 signaling in endothelium may limit metastases in breast and other cancers and highlight the unique capabilities of our microfluidic device to advance studies of the intravascular microenvironment in metastasis.     

Analysis of Detection Processes for Breast Cancer

Most existing records of detection processes for breast cancer are in the form of cancer registries or are results of large clinical trials. Statistical modelling can be applied to these data sets to study various properties of breast cancer. In particular we estimate the probability of cure given the size of the tumour at detection, the distribution of tumour growth rates and the distribution of the size of the tumour at detection. There has been a strong recent interest in early detection methods. These consist of giving regular examinations, called screenings. The effect of screening design on the probability of cure is considered. The results of an existing screening trial are used to derive another estimate of the tumour growth rate distribution which agrees well both with our earlier estimate and the most widely used empirical estimate in the literature. The calculation of lead time, which is the time gained in detection when screenings are given, is also discussed.     

A Hybrid Plasmonic Bimetallic Nanoshell-Microsphere Sensor for Cancer Market Protein Detection

Plasmonics - In this paper, the detection of a thyroid cancer market (Thyroglobulin, Tg) protein has demonstrated by using a hybrid plasmonic bimetallic nanoshell-microsphere sensor based on the...     

Alphabetic-Core Assisted Microstructure Fiber Based Plasmonic Biosensor

Light control capability of photonic crystal fiber (PCF) is a unique feature which can be applied to improve biosensing and plasmonic performance. Here, we reported alphabetic-core microstructure fiber-based plasmonic biosensor. Three different alphabetic R-, M-, and S-shaped cores of PCF-based plasmonic microstructures show controllable light propagation to enhance biosensor sensitivity and resolution. The light-guiding properties and sensing performance are investigated numerically using the finite element method (FEM). The proposed R-shaped core (RSC), M-shaped core (MSC), and S-shaped core (SSC) PCF-based plasmonic sensors show the maximum wavelength and amplitude sensitivities of 12,000, 11,000, 10,000 nm/RIU and 478, 533, and 933 RIU⁻¹, respectively, in the refractive index (RI) range of 1.33 to 1.40. The sensors also exhibit promising wavelength resolution of 8.33 × 10⁻⁶, 9.09 × 10⁻⁶, and 1.0 × 10⁻⁶ RIU, with figure of merit (FOM) of 108, 143, and 217 RIU⁻¹ for RSC, MSC, and SSC PCFs, respectively. The tunable sensing performance is also observed in design structures due to controllable light traveling path and their interaction with analytes. The proposed alphabetic-core PCF SPR sensors would be a promising candidate for the application of light controlling, trapping in microscale environment, and biosensing.

     

Carcinoembryonic Antigen in Patients With Breast or Colon Cancer

The rationale and results of clinical use of carcinoembryonic antigen (CEA) tests in patients with carcinoma of the breast and colon deserve review. Plasma CEA levels have been found to correlate with the extent of tumor invasion and site of metastatic spread, and CEA titers have diagnostic and prognostic value. Although postresectional serial CEA testing is not as useful in cases of breast carcinoma, in cases of carcinoma of the colon it may indicate recurrence or progression of the lesion. However, there are limitations and CEA results should be interpreted in conjunction with other clinical information.     

微流控芯片在乳腺癌骨转移研究中的应用

乳腺癌骨转移患者死亡率高达70%～80%,目前缺乏有效的治疗药物.微流控芯片技术能够有效模拟骨组织的生化和生物物理微环境,便捷地实现模拟骨微环境中乳腺癌骨转移的研究,这将为探索乳腺癌骨转移的细胞和分子机制、进而进行抗乳腺癌骨转移药物高通量筛选提供有价值的技术方法和平台.本综述简要介绍了乳腺癌骨转移的分子机制和治疗药物研究现状,详细阐述了乳腺癌骨转移的微流控芯片模型,分析了基于微流控芯片技术进行抗乳腺癌骨转移药物高通量筛选的优势和挑战,旨在为乳腺癌骨转移机制研究和药物筛选提供参考.     

One Dimensional Plasmonic Grating: High Sensitive Biosensor

We report a simple 1D grating device fabrication on ～50 nm gold (Au) film deposited on glass, which is employed as a high performance refractive index (RI) sensor by exploiting the surface plasmon polaritons (SPP) excited by the grating device along the Au/analyte interface. A finite element analysis (FEA) method is employed to maximize the sensitivity of the sensor for a fixed period and thickness of a gold film and its close correspondence with experiment has given the insight for high sensitivity and enhanced transmission. Significantly, in the context of economic design and performance, it is shown that an optimally designed and fabricated 1D grating can be as sensitive as 524 nm/RIU (linearity RI?=?1.33303 to 1.47399), which is remarkably higher than existing reports operating in a similar wavelength region.     

Biosensor Systems for Antibiotic Detection

Antibiotics are widely used in medicine, veterinary medicine, and the food industry. However, the active use of antibacterial drugs leads to environmental pollution. In this regard, there is a great need for monitoring and determining antibiotics in various environments such as drinking water, food, drinks, waste water from pharmaceutical factories, etc. A number of methods, including those based on biosensors, have been developed to determine antibiotics. Biosensor methods of analysis are widely used and are an integral part of environmental monitoring. Electrochemical, optical, acoustic, microbial biosensors, immuno- and aptasensors, as well as sensors based on molecularly imprinted polymers are in the most demand for the analysis of antibiotics. This article provides a brief overview of biosensor methods and approaches for the determination of antibiotics. The most promising biosensor systems for determining antibacterial drugs were analyzed.

     

A Tunable Plasmonic Refractive Index Sensor with Ultrabroad Sensing Range for Cancer Detection

Plasmonics - Contribution of quantum dots (QDs) and nano dots (NDs) in boosting the plasmonic behavior of noble metal nano cavity structure and its refractive index (RI) sensing is...     

Circulating microRNAs as Specific Biomarkers for Breast Cancer Detection

Background

We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection.

Methodology/Principal Findings

TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%.

Conclusions

These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.     

Cancer Detection with Surface Plasmon Resonance-Based Photonic Crystal Fiber Biosensor

Plasmonics - In this study, early cancer detection of a single living cell is investigated by employing a surface plasmon resonance (SPR)-based photonic crystal fiber (PCF) biosensor structure. The...     

All-Optical Tunable Plasmonic Biosensor Made of Graphene and Metamaterial

Plasmonics - We demonstrate a novel, label-free and real-time tunable infrared biosensor by employing surface-plasmon polaritons in asymmetric Mach–Zehnder interferometer. The waveguides...     

分子诊断技术在乳腺癌检测中的最新进展

乳腺癌是一种严重危害女性健康的恶性肿瘤,对其致病基因的检测有助于肿瘤早期诊断、精准治疗及预后评估.本文总结了近年来乳腺癌相关的热点基因,并对相关基因的分子诊断技术、检测方法及应用进行了综述.首次评述了数字PCR方法用于乳腺癌分子检测的进展.全面对比不同分子诊断技术的差别与优缺点,为乳腺癌关键基因的检测提供指导建议与理论支持,并对未来发展趋势做出展望.     

Development of a Biosensor for Detection of Pleural Mesothelioma Cancer Biomarker Using Surface Imprinting

Hyaluronan-linked protein 1 (HAPLN1) which has been shown to be highly expressed in malignant pleural mesotheliomas (MPM), was detected in serum using an electrochemical surface-imprinting method. First, the detection method was optimized using Bovine serum albumin (BSA) as a model protein to mimic the optimal conditions required to imprint the similar molecular weight protein HAPLN1. BSA was imprinted on the gold electrode with hydroxyl terminated alkane thiols, which formed a self-assembled monolayer (SAM) around BSA. The analyte (BSA) was then washed away and its imprint (empty cavity with shape-memory) was used for detection of BSA in a solution, using electrochemical open-circuit potential method, namely potentiometry. Factors considered to optimize the conditions include incubation time, protein concentration, limit of detection and size of electrode. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to confirm selectivity of imprints. With the obtained imprinting control parameters, HAPLN1 was imprinted in duplicate and the detection of spiked HAPLN1 was successfully conducted in serum.     

Plasma MicroRNA Panel for Minimally Invasive Detection of Breast Cancer

Over the last few years, circulating microRNAs (miRNAs) have emerged as promising novel and minimally invasive markers for various diseases, including cancer. We already showed that certain miRNAs are deregulated in the plasma of breast cancer patients when compared to healthy women. Herein we have further explored their potential to serve as breast cancer early detection markers in blood plasma. Circulating miR-127-3p, miR-376a and miR-652, selected as candidates from a miRNA array-based screening, were found to be associated with breast cancer for the first time (n = 417). Further we validated our previously reported circulating miRNAs (miR-148b, miR-376c, miR-409-3p and miR-801) in an independent cohort (n = 210) as elevated in the plasma of breast cancer patients compared to healthy women. We described, for the first time in breast cancer, an over-representation of deregulated miRNAs (miR-127-3p, miR-376a, miR-376c and miR-409-3p) originating from the chromosome 14q32 region. The inclusion of patients with benign breast tumors enabled the observation that miR-148b, miR-652 and miR-801 levels are even elevated in the plasma of women with benign tumors when compared to healthy controls. Furthermore, an analysis of samples stratified by cancer stage demonstrated that miR-127-3p, miR-148b, miR-409-3p, miR-652 and miR-801 can detect also stage I or stage II breast cancer thus making them attractive candidates for early detection. Finally, ROC curve analysis showed that a panel of these seven circulating miRNAs has substantial diagnostic potential with an AUC of 0.81 for the detection of benign and malignant breast tumors, which further increased to 0.86 in younger women (up to 50 years of age).     

血清CA153、TK1、TSGF联合检测对乳腺癌诊断的价值

目的：探讨细胞表面糖蛋白（CA153）、胸苷激酶（TKl）、肿瘤生长因子（TSGF）等联合检测在乳腺癌诊断中的应用价值。方法：73例确诊为乳腺癌患者的血清标本作为实验组;66例乳腺良性疾病（包括乳腺纤维瘤、囊肿、增生等）及50例健康人群血清标本作为对照组。采用电化学发光法检测血清CAl53,免疫化学发光法检测TKl,化学显示法检测TSGF的表达。结果：血清CAl53、TKl及TSGF对乳腺癌的敏感性分别为54．8％、53．4％及79．5％,特异性分别为87．9％、81．8％及83．3％;血清CAl53、TKl、TSGF联合检测乳腺癌的敏感性为89．0％,特异性为92．4％。结论：与单项指标检测相比,多个指标联合检测提高了对乳腺癌早期诊断的敏感性．同时又有较好的特异性．有助于良、恶乳腺疾病的鉴别．具有一定的临床应用价值．