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Early diagnosis of liver cancer plays a significant role in reducing its high mortality. In this preliminary study, the feasibility of using serum surface-enhanced Raman spectroscopy (SERS) to identify liver cancer was studied. Serum samples were obtained from liver cancer patients and healthy controls. The differences between the SERS spectra of pre-operation and post-operation of liver cancer patients were also analyzed. The general shape and trend of SERS spectra of health control and liver cancer patients were similar. Multivariate analysis, e.g., PLS-SVM, might be useful for the discrimination of serum SERS spectra of pre-operation and post-operation.

In this paper, optical coherence tomography (OCT) and surface-enhanced Raman spectroscopy (SERS) were used to characterize normal knee joint (NKJ) tissue and knee osteoarthritis (KOA) tissue ex vivo. OCT images show that there is a clear hierarchical structure in NKJ tissue, including surface layer, transitional layer, radiation layer and cartilage matrix calcification layer tissue structure, while the hierarchical structure of KOA tissue is not clear and unevenly distributed, and the pathological tissues at different stages also show significant differences. SERS shows that NKJ tissue and mild osteoarthritic knee cartilage (MiKOA) tissue have strong characteristic Raman peaks at 964, 1073 (1086), 1271, 1305, 1442, 1660 and 1763[Formula: see text]cm[Formula: see text]. Compared with the Raman spectrum of NKJ tissue, the Raman characteristic peaks of MiKOA tissue have some shifts, moving from 1073[Formula: see text]cm[Formula: see text] to 1086[Formula: see text]cm[Formula: see text] and from 1542[Formula: see text]cm[Formula: see text] to 1442[Formula: see text]cm[Formula: see text]. There is a characteristic Raman peak of 1271[Formula: see text]cm[Formula: see text] in MiKOA tissue, but not in NKJ tissue. Compared with NKJ tissue, severely degenerated cartilage (SdKOA) tissues show some new SERS peaks at 1008, 1245, 1285, 1311 and 1321[Formula: see text]cm[Formula: see text], which are not seen in SERS spectra of NKJ tissue. Principal component analysis (PCA) was used to analyze the Raman spectra of 1245–1345[Formula: see text]cm[Formula: see text] region. The results show that PCA can distinguish NKJ, MiKOA and SdKOA tissues and the accuracy is about 90%. These results indicate that OCT can clearly distinguish NKJ, MiKOA, moderate osteoarthritic knee cartilage (MoKOA) and SdKOA tissue, while SERS can provide further judgment basis. The results also prove that the contents of protein and polysaccharide in knee tissue are changed during the pathological process of knee tissue, which is the cause of pain caused by poor friction in knee joint during movement.

Renal ischemia–reperfusion (IR) is inevitable in partial nephrectomy and kidney transplantation. Acute tubular necrosis (ATN) induced by renal IR causes the loss of functional units in the kidney, pathologically presenting as the nonhomogeneous distribution of normal uriniferous tubules and usually used to characterize kidney activity. Optical coherence tomography (OCT) has been proven to have the ability to image the kidney microstructure in vivo and in real time. However, a fast image analysis method is needed for clinical application purpose. In this work, a new method for assessing renal IR injury was developed using a fractal-dimension-based texture of the OCT kidney image. Thirty-five Wistar rats were divided into seven groups for renal ischemia–reperfusion: control and various ischemia-time groups. A time series of 3D OCT kidney images was obtained. We calculated the fractal dimension (FD) of OCT en face images and found that the value increased gradually and finally became stable after 90 min of reperfusion. The stable value in the long-ischemia-time group was smaller than that in the short-ischemia-time group. The FD value of the OCT kidney image was highly responsive to renal IR injury. The proposed method is promising for a fast diagnostic application.

Introduction: Nasopharyngeal carcinoma, an epithelial-derived malignant tumor which because of its anatomical location and atypical early symptoms, when diagnosed invasion and metastasis often have occurred. This requires a better understanding of the development mechanism, identifying diagnostic markers, and developing new treatment strategies. Objective: To study the relationship of LMP1 and Cripto-1 in nasopharyngeal carcinoma. Methods: The expression of LMP1 and Cripto-1 in specimens obtained from nasopharyngeal carcinoma patients (n = 42) and nasopharyngitis patients (n = 22) were examined. The expression of LMP1 and Cripto-1 in LMP1-negative and LMP1-positive (CNE1-LMP1) cells were also examined. Results: The expression of LMP1 and Cripto-1 was significantly higher in nasopharyngeal carcinoma than in nasopharyngitis (p

The mechanical properties of cells could serve as an indicator for disease progression and early cancer diagnosis. This study utilized atomic force microscopy (AFM) to measure the viscoelastic properties of ovarian cancer cells and then examined the association with the invasion of ovarian cancer at the level of living single cells. Elasticity and viscosity of the ovarian cancer cells OVCAR-3 and HO-8910 are significantly lower than those of the human ovarian surface epithelial cell (HOSEpiC) control. Further examination found a dramatic increase of migration/invasion and an obvious decease of microfilament density in OVCAR-3 and HO-8910 cells. Also, there was a significant relationship between viscoelastic and biological properties among these cells. In addition, the elasticity was significantly increased in OVCAR-3 and HO-8910 cells after the treatment with the anticancer compound echinomycin (Ech), while no obvious change was found in HOSEpiC cells after Ech treatment. Interestingly, Ech seemed to have no effect on the viscosity of the cells. Ech significantly inhibited the migration/invasion and significantly increased the microfilament density in OVCAR-3 and HO-8910 cells, which was significantly related with the elasticity of the cells. An increase of elasticity and a decrease of invasion were found in OVCAR-3 and HO-8910 cells after Ech treatment. Together, this study clearly demonstrated the association of viscoelastic properties with the invasion of ovarian cancer cells and shed a light on the biomechanical changes for early diagnosis of tumor transformation and progression at single-cell level.

The objective of this paper is to evaluate the penetration and accumulation of SiO2 nanoparticles (NPs) in vitro human placental tissue as a function of NP size and electroporation (EP) and microneedle (MN) treatments. The results show that the penetration and accumulation of SiO2 NPs has a significant influence on the optical properties. Optical coherence tomography (OCT) monitoring and diffuse reflectance (DR) spectra measurements indicate that 30 nm SiO2 NPs have a tendency to generate greater signal intensities, while 15 nm NPs penetrated faster and had a higher penetration depth. The reduction in average attenuation coefficients of human placental tissue when the SiO2 NPs size is constant is found to show the following trend: SiO2 NPs in combination with EP and MN treatment > SiO2 NPs in combination with MN > SiO2 NPs with EP > only SiO2 NPs. It can be concluded that EP and MN treatments dramatically increase the penetration of SiO2 NPs into human placental tissue. The results prove that OCT and DR spectra can be combined with EP and MN treatments to establish a theoretical basis for the safe use of SiO2 NPs on human placental tissue and can potentially become a powerful tool for early diagnosis and monitoring of tissue diseases.

Dye-doped polymer microdroplet resonators were fabricated by injecting dye solutions into a low refractive index UV curable polymer. The self-assembled microdroplets had the various sizes ranging from 5 to 200 μm. Pumped by a pulse laser, whispering-gallery-mode (WGM) lasing emission from the microresonators was achieved. Experimental results show that the microresonators had the advantages of high-Q factors, low lasing thresholds, and good long-term stabilities. The injection method can provide a promising approach for fabricating the high-Q WGM microresonators, which had some potential applications in the fields of tunable microlasers and on-chip biosensing system.

We propose and theoretically investigate an all-dielectric bowtie whisperinggallery-mode (WGM) resonator which consists of two tip-to-tip coupled semiconductor nanorings with triangular cross section separated by low refractive index material gap. Mode splitting of symmetric WGM and antisymmetric WGM is observed and analyzed. Due to extremely field enhancements by the “slot” and “tip” effects, strong localization of light in the gap of symmetric WGMs leads to ultrasmall modal volume of 0.3μm3. This value is two orders of magnitude smaller than that in toroidal microresonator which is the typical WGM microcavity with tight mode confinement. Importantly, large amount of light confined in the gap in bowtie WGM resonator not only suppresses the radiation loss (radiation-loss-related quality factor is above 108), but also makes it as an ideal platform for Purcell effect enhancement, ultrasensitive sensing, and optical trapping of nanoparticles. Calculation results show that Purcell factor can reach to 108 at room temperature when assuming quantum dots or atoms placed in the gap. Refractive index sensitivity is improved to 700 nm/RIU as compared with conventional slot waveguide with rectangular cross section. The optical gradient force is greatly enhanced and allows efficient trapping of single nanoscale particle with diameter of 5 nm even at a relatively large gap of 100 nm.

Latent membrane protein 1 (LMP1) is known as an oncoprotein in nasopharyngeal carcinoma (NPC) cells, which is considered to have a strong association with growth, invasion and metastasis of NPC cells through lipid rafts. Methyl-β-cyclodextrin (MβCD) can disrupt lipid rafts through cholesterol depletion. In this study, we revealed that MβCD induced apoptosis in two kinds of NPC cells including CNE1 cells, a LMP1-negative nasopharyngeal squamous carcinoma cell line, and CNE1-LMP1 cells, a LMP1-positive nasopharyngeal squamous carcinoma cell line. Furthermore, the impact of MβCD on LMP1 was investigated by fluorescence resonance energy transfer (FRET) method in NPC cells. Synchronized tempo-spatial and spectral detection of LMP1/LMP1 interaction were performed using fluorescence microscope and spectrograph. FRET efficiency indicated that LMP1/LMP1 interaction gradually enhanced after MβCD treatment. MTT assays showed that MβCD caused strong cytotoxicity in CNE1 cells, but caused relatively weaker cytotoxicity in CNE1-LMP1 cells, which indicated that LMP1 may regulate sensitivity of NPC cells to MβCD. Then, detection of cleaved caspase-3 in two kinds of NPC cells indicated that LMP1 may inhibit activation of caspase-3. These results strongly suggested that MβCD can induce apoptosis of NPC cells, but enhancing of LMP1/LMP1 interaction may likely resist apoptosis through inhibiting cleavage of caspase-3.

The binding interaction between tetra-(p-sulfoazophenyl-4-aminosulfonyl)-substituted aluminum (III) phthalocyanine (AlPc), and two-serum albumins (bovine serum albumin (BSA) and human serum albumin (HSA)) has been investigated. AlPc could quench the intrinsic fluorescence of BSA and HSA through a static quenching process. The primary and secondary binding sites of AlPc on BSA were domain I and III of BSA. The primary binding site of AlPc on HSA was domain I, and the secondary binding sites of AlPc on HSA were found at domains I and II. Our results suggest that AlPc readily interact with BSA and HSA implying that the amphiphilic substituents AlPc may contribute to their transportation in the blood.

Optical whispering-gallery-mode (WGM) microresonator-based sensors with high sensitivity and low detection limit down to single unlabeled biomolecules show high potential for disease diagnosis and clinical application. However, most WGM microresonator-based sensors, which are packed in a microfluidic cell, are a “closed„ sensing configuration that prevents changing and sensing the surrounding liquid refractive index (RI) of the microresonator immediately. Here, we present an “open„ sensing configuration in which the WGM microdisk laser is directly covered by a water droplet and pumped by a water-immersion-objective (WIO). This allows monitoring the chemical reaction progress in the water droplet by tracking the laser wavelength. A proof-of-concept demonstration of chemical sensor is performed by observing the process of salt dissolution in water and diffusion of two droplets with different RI. This WIO pumped sensing configuration provides a path towards an on-chip chemical sensor for studying chemical reaction kinetics in real time.

Far-field fluorescence microscopy has made great progress in the spatial resolution, limited by light diffraction, since the super-resolution imaging technology appeared. And stimulated emission depletion (STED) microscopy and structured illumination microscopy (SIM) can be grouped into one class of the super-resolution imaging technology, which use pattern illumination strategy to circumvent the diffraction limit. We simulated the images of the beads of SIM imaging, the intensity distribution of STED excitation light and depletion light in order to observe effects of the polarized light on imaging quality. Compared to fixed linear polarization, circularly polarized light is more suitable for SIM on reconstructed image. And right-handed circular polarization (CP) light is more appropriate for both the excitation and depletion light in STED system. Therefore the right-handed CP light would be the best candidate when the SIM and STED are combined into one microscope. Good understanding of the polarization will provide a reference for the patterned illumination experiment to achieve better resolution and better image quality.

Optical microscopy allows us to observe the biological structures and processes within living cells. However, the spatial resolution of the optical microscopy is limited to about half of the wavelength by the light diffraction. Structured illumination microscopy (SIM), a type of new emerging super-resolution microscopy, doubles the spatial resolution by illuminating the specimen with a patterned light, and the sample and light source requirements of SIM are not as strict as the other super-resolution microscopy. In addition, SIM is easier to combine with the other imaging techniques to improve their imaging resolution, leading to the developments of diverse types of SIM. SIM has great potential to meet the various requirements of living cells imaging. Here, we review the recent developments of SIM and its combination with other imaging techniques.

Liquid droplet and quasi-droplet whispering gallery mode (WGM) microcavities have been widely studied recently for the enhanced spatial overlap between the liquid and WGM field, especially in sensing applications. However, the fragile cavity structure and the evaporation of liquid limit its practical applications. Here, stable, packaged, quasi-droplet and droplet microcavities are proposed and fabricated for thermal sensing with high sensitivity. The sensitivity and electromagnetic field intensity distribution are analyzed by Mie theory, and a quantified definition of the quasi-droplet is presented for the first time to the best of our knowledge. By doping dye material directly into the liquid, lasing packaged droplet and quasi-droplet microcavity sensors with a high thermal sensitivity of up to 205.3 pm/°C are experimentally demonstrated. The high sensitivity, facile fabrication, and mechanically robust properties of the optofluidic, packaged droplet microresonator make it a promising candidate for future integrated photonic devices.

Histopathology forms the gold standard for the diagnosis of breast cancer. Multiphoton microscopy (MPM) has been proposed to be a potentially powerful adjunct to current histopathological techniques. A label-free imaging based on two- photon excited fluorescence and second-harmonic generation is developed for differentiating normal breast tissues, benign, as well as breast cancer tissues. Human breast biopsies (including human normal breast tissues, benign as well as breast cancer tissues ) that are first imaged (fresh, unfixed, and unstained) with MPM and are then processed for routine H-E histopathology. Our results suggest that the MPM images, obtained from these unprocessed biopsies, can readily distinguish between benign lesions and breast cancers. In the tissues of breast cancers, MPM showed that the tumor cells displayed marked cellular and nuclear pleomorphism. The tumor cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, infiltrated into disrupted connective tissue, leading to the loss of second-harmonic generation signals. For breast cancer, MPM diagnosis was 100% correct because the tissues of breast cancers did not have second-harmonic generation signals in MPM imaging. On the contrary, in benign breast masses, second-harmonic generation signals could be seen easily in MPM imaging. These observations indicate that MPM could be an important potential tool to provide label-free noninvasive diagnostic impressions that can guide surgeon in biopsy and patient management.

Since changes in the basement membranes are the critical indicators for differentiating normal, precancerous, and cancerous colonic tissues, direct visualization of these warning signs is essential for the early diagnosis and treatment of colonic cancer. Here, we present that second harmonic generation (SHG) microscopy can probe the changes of basement membranes in different colonic cancer stages. Our results also show the capability of using the quantitative analyses of images for quantifying these changes in different cancer stages. These results suggest that SHG microscopy has the potential in label-freely imaging the changes of basement membranes for effectively distinguishing between normal, precancerous, and cancerous colonic tissues. To our knowledge, this is the first demonstration of the dynamics of basement membrane changes in different colonic cancer stages using entirely intrinsic source of contrast.

The aim of this study is to develop a light-emitting diode- (LED-) based illumination system that can be used as an alternative light source for in vitro photodynamic therapy (PDT). This illumination system includes a red LED array composed of 70 LEDs centered at 643 nm, an air-cooling unit, and a specific-designed case. The irradiance as a function of the irradiation distance between the LED array and the sample, the homogeneity and stability of irradiation, and the effect of long-time irradiation on culture medium temperature were characterized. Furthermore, the survival rate of the CNE1 cells that sensitized with 5-aminolevulinic acid after PDT treatment was evaluated to demonstrate the efficiency of the new LED-based illumination system. The obtained results show that the LED-based illumination system is a promising light source for in vitro PDT that performed in standard multiwell plate.

In this paper, by introducing a new flux variable, two decoupled and linearized blockcentered finite difference methods are developed and analyzed for the nonlinear symmetric regularized long wave equation, where the two-step backward difference formula and Crank-Nicolson temporal discretization combined with linear extrapolation technique are employed. Under a reasonable time stepsize ratio restriction, i.e., t = o(h1=4), second-order convergence for both the primal variable and its flux are rigorously proved on general non-uniform spatial grids. Moreover, based upon the convergence results and inverse estimate, stability of two methods are also demonstrated. Ample numerical experiments are presented to confirm the theoretical analysis. [ABSTRACT FROM AUTHOR]