Coupled-mode induced transparency via Ohmic heating in a single polydimethylsiloxane-coated microbubble resonator.

We demonstrate an approach for the realization of coupled-mode induced transparency (CMIT) in a hybrid polydimethylsiloxane (PDMS)-coated silica microbubble resonator, with an Au microwire inserted in the hollow channel. Owing to the large negative thermo-optics coefficient of PDMS, different radial order modes with opposite thermal sensitivities can coexist in this hybrid microcavity. By applying a current through the Au microwire, which acts as a microheater, the generated Ohmic heating could thermally tune the resonance frequencies and the frequency detuning of the coupled mode to achieve controllable CMIT. This platform offers an efficient and convenient way to obtain controllable CMIT for applications, such as label-free biosensing and quantum information processing.

Optofluidic microbubble Fabry-Pérot cavity.

An optofluidic microbubble Fabry-Pérot (OMBFP) cavity was investigated. In contrast to plane-plane FP (PPFP) cavities, the optical mode confinement and stability in an OMBFP were significantly enhanced. The optical properties of the OMBFP cavity, including the quality (Q) factor, effective mode area, mode distribution as a function of the core refractive index, microbubble position, and mirror tilt angle, were investigated systematically using the finite element method. In optofluidic lasing experiments, a low lasing threshold of 1.25 µJ/mm2, which was one order magnitude lower than that of the PPFP, was achieved owing to improved modal lateral confinement. Since the microbubble acts as a micro-lens and microfluidic channel in the parallel FP cavity, mode selection and cell-dye laser were easily realized in the OMBFP cavity.

Tunable optofluidic liquid metal core microbubble resonator.

This study introduces design and coupling techniques, which bridge an opaque liquid metal, optical WGM mode, and mechanical mode into an opto-mechano-fluidic microbubble resonator (MBR) consisting of a dielectric silica shell and liquid metal core. Benefiting from the conductivity of the liquid metal, Ohmic heating was carried out for the MBR by applying current to the liquid metal to change the temperature of the MBR by more than 300 °C. The optical mode was thermally tuned (>3 nm) over a full free spectral range because the Ohmic heating changed the refractive index of the silica and dimeter of the MBR. The mechanical mode was thermally tuned with a relative tuning range of 9% because the Ohmic heating changed the velocity and density of the liquid metal.

SERS-based cascade amplification bioassay protocol of miRNA-21 by using sandwich structure with biotin-streptavidin system.

In our bioassay protocol, the Ag@4MBA@DNA-biotin probes were synthesized by linking biotin-modified DNA and 4-mercaptobenzoic acid-covered Ag nanoparticles, and the Si@Ag@anti-digoxin/digoxin-DNA substrate was fabricated by immune linking of digoxin-DNA and anti-digoxin immobilized on a Ag-coated wafer. Then, the probes, miRNA-21 and the substrate were constructed into a "sandwich structure" to detect the variation in the SERS signals with respect to miRNA-21 concentrations. Next, streptavidin and extra probes were alternately introduced to implement the cascade amplification of the SERS signal to increase the detection sensitivity. The results show that the limit of detection (LOD) with cascade amplification is remarkably improved from 97.81 pM to 38.02 fM, which is three orders of magnitude higher than the original data without cascade amplification. Furthermore, the SERS-based cascade amplification mechanism was analyzed and is attributed to the "hot spots effect" of the noble metal nanostructure. The biotin-streptavidin (B-S) system was introduced into the SERS detection platform, and the novel SERS-based cascade amplification bioassay protocol has significant creativity for the detection of nucleic acids.

Controllable and selective single-mode lasing in polymer microbottle resonator.

We report a single-mode dye-doped polymer microbottle resonator (MBR) laser. The selective single-mode lasing from different order whispering gallery modes is achieved by precisely controlling the axial and radial coupling position between a tapered nanofiber and an MBR, respectively. The side-mode suppression ratio is above 20 dB. By doping different fluorescence dyes into the MBR, single-mode lasers at various colors are demonstrated.

Extreme terahertz electric-field enhancement in high-Q photonic crystal slab cavity with nanoholes.

A one-dimensional photonic-crystal (PC) cavity with nanoholes is proposed for extreme enhancement of terahertz (THz) electric fields using the electromagnetic (EM) boundary conditions. Both slot (for the perpendicular component of the electric displacement field) and anti-slot (for the parallel component of the electric field) effects contribute to the considerable field enhancement. The EM energy density can be enhanced by a factor of (εh/εl)2 in the high-refractive-index material, where εh and εl are the permittivities of the high- and low-refractive-index materials, respectively. Correspondingly, the mode volume can be reduced by a factor of 288, compared with a conventional THz PC cavity, and is three orders of magnitude smaller than the diffraction limitation. Further, the proposed THz cavity design also supports modes with high quality factors (Q) > 104, which induces strong Purcell enhancement by a factor exceeding 106. Our THz cavity design is feasible and attractive for experimental demonstrations, because the semiconductor layer in which the EM is maximized can naturally be filled with quantum-engineered active materials. Thus, the proposed design can possibly be used to develop room-temperature coherent THz radiation sources.

Packaged Droplet Microresonator for Thermal Sensing with High Sensitivity.

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.

PINK1 is required for timely cell-type specific mitochondrial clearance during Drosophila midgut metamorphosis.

Mitophagy is the selective degradation of mitochondria by autophagy, which is an important mitochondrial quality and quantity control process. During Drosophila metamorphosis, the degradation of midgut involves a large change in length and organization, which is mediated by autophagy. Here we noticed a cell-type specific mitochondrial clearance process that occurs in enterocytes (ECs), while most mitochondria remain in intestinal stem cells (ISCs) during metamorphosis. Although PINK1/PARKIN represent the canonical pathway for the elimination of impaired mitochondria in varied pathological conditions, their roles in developmental processes or normal physiological conditions have been less studied. To examine the potential contribution of PINK1 in developmental processes, we monitored the dynamic expression pattern of PINK1 in the midgut development by taking advantage of a newly CRISPR/Cas9 generated knock-in fly strain expressing PINK1-mCherry fusion protein that presumably recapitulates the endogenous expression pattern of PINK1. We disclosed a spatiotemporal correlation between the expression pattern of PINK1 and the mitochondrial clearance or persistence in ECs or ISCs respectively. By mosaic genetic analysis, we then demonstrated that PINK1 and PARKIN function epistatically to mediate the specific timely removal of mitochondria, and are involved in global autophagy in ECs during Drosophila midgut metamorphosis, with kinase-dead PINK1 exerting dominant negative effects. Taken together, our studies concluded that the PINK1/PARKIN is crucial for timely cell-type specific mitophagy under physiological conditions and demonstrated again that Drosophila midgut metamorphosis might serve as an elegant in vivo model to study autophagy.

Effects of different-intensity laser acupuncture at two adjacent same-meridian acupoints on nitric oxide and soluble guanylate cyclase releases in human.

OBJECTIVES: The aim of this study was to detect the influences of LA at nonacupoint and two adjacent acupoints of pericardium meridian on the releases of NO and sGC in 20 healthy subjects. METHODS: Different intensities (12, 24, 48 mW) of infrared laser were used for irradiating Jianshi (PC5), Ximen (PC4) acupoints and nonacupoint for 20, 40 minutes, respectively. Semi-circular tubes were taped to the skin surface and filled with NO-scavenging compound for 20 minutes to capture NO and sGC, which were measured using spectrophotometry in a blinded fashion. RESULTS: As the increase in the intensity of LA stimulation, the levels of NO releases over acupoints all were significantly increased, NO releases in nonacupoints following the same treatment only changed slightly, sGC amounts were observably enhanced over acupoints, but did not any change in nonacupoint area. Different intensities of LA treatments can sensitively affect the NO and sGC releases over acupoints. This indicated that LA-induced releases of the NO and sGC were specific to acupoints. CONCLUSIONS: This is the first evidence reporting that LA induced significant elevations of NO-sGC releases over acupoints, and the enhanced signal molecules contribute to local circulation, which improves the beneficial effects of the therapy.

Wide-field microscopic FRET imaging using simultaneous spectral unmixing of excitation and emission spectra.

Simultaneous spectral unmixing of excitation and emission spectra (ExEm unmixing) has the inherent ability to resolve donor emission, fluorescence resonance energy transfer (FRET)-sensitized acceptor emission and directly excited acceptor emission. We here develop an ExEm unmixing-based quantitative FRET measurement method (EES-FRET) independent of excitation intensity and detector parameter setting. The ratio factor (rK), predetermined using a donor-acceptor tandem construct, of total acceptor absorption to total donor absorption in excitation wavelengths used is introduced for determining the concentration ratio of acceptor to donor. We implemented EES-FRET method on a wide-field microscope to image living cells expressing tandem FRET constructs with different donor-acceptor stoichiometry.

In vitro investigation on Ho:YAG laser-assisted bone ablation underwater.

Liquid-assisted hard tissue ablation by infrared lasers has extensive clinical application. However, detailed studies are still needed to explore the underlying mechanism. In the present study, the dynamic process of bubble evolution induced by Ho:YAG laser under water without and with bone tissue at different thickness layer were studied, as well as its effects on hard tissue ablation. The results showed that the Ho:YAG laser was capable of ablating hard bone tissue effectively in underwater conditions. The penetration of Ho:YAG laser can be significantly increased up to about 4 mm with the assistance of bubble. The hydrokinetic forces associated with the bubble not only contributed to reducing the thermal injury to peripheral tissue, but also enhanced the ablation efficiency and improve the ablation crater morphology. The data also presented some clues to optimal selection of irradiation parameters and provided additional knowledge of the bubble-assisted hard tissue ablation mechanism.

In vitro assessment of effects of hyperglycemia on the optical properties of blood during coagulation using optical coherence tomography.

No published reports have demonstrated the capability of the optical coherence tomography technique for quantifying the optical coherence tomography signal slope, 1/e light penetration depth, and attenuation coefficient of hyperglycemic blood by an in vitro assessment. The purpose of this study was to investigate the effects of hyperglycemia on optical properties during in vitro blood coagulation by optical coherence tomography. Normal whole blood acted as the control group. After 1-h coagulation, the average optical coherence tomography signal slope decreased approximately 23.3 and 16.7%, and the 1/e light penetration depths increased approximately 21.5 and 19.2% for the control and hyperglycemic groups, respectively. It could be seen from the 1/e light penetration depth evolution curves that the blood coagulation time was about (425 ± 19) s for normal whole blood and (367 ± 15) s for the hyperglycemic blood. The coagulation time decreased 13.6% for the hyperglycemic blood compared with that for normal whole blood. There was statistically significant difference in blood coagulation time between the hyperglycemic and normal whole blood (p < 0.05). The results suggested that hyperglycemia has a procoagulant effect. Our experiment was the first reported study of monitoring hyperglycemic blood coagulation using OCT. We conclude that OCT is potential technique to quantify and follow the liquid-gel transition of hyperglycemic blood coagulation.

Real-time optical diagnosis for surgical margin in low rectal cancer using multiphoton microscopy.

BACKGROUND: Multiphoton microscopy (MPM), based on advances in the field of nonlinear optics and femtosecond lasers, has been shown to provide detailed real-time information on tissue architecture and cell morphology in live tissue. The purpose of this study was to evaluate the feasibility of using MPM to make real-time optical diagnoses for surgical margins in low rectal cancers. METHODS: Thirty fresh, unfixed, and unstained full-thickness surgical margins of low rectal cancers underwent MPM examination and then went through intraoperative frozen procedures and routine pathological procedures. MPM images were compared with the gold standard hematoxylin-eosin (H-E) stained images. RESULTS: MPM images were acquired by two channels: broadband autofluorescence from cells and second harmonic generation (SHG) from tissue collagen. Peak multiphoton signal intensity was detected in mucosa excited at 800 nm. There were significant differences between negative surgical margins and positive surgical margins under MPM examination. In negative surgical margins, MPM revealed regular tissue architecture and cell morphology, including a typical foveolar pattern with central, round crypt openings, and glands lined by epithelial and goblet cells. SHG signals could be detected around the glands. In positive surgical margins, MPM demonstrated irregular tubular structures, reduced stroma, and cellular and nuclear pleomorphisms. Cancer cells were characterized by an irregular size and shape, enlarged nuclei, and an increased nuclear-cytoplasmic ratio. SHG signals were significantly decreased in positive surgical margins compared with negative surgical margins. MPM images were comparable to H-E stained images. CONCLUSIONS: We demonstrated the feasibility of using MPM to make real-time optical diagnoses for surgical margins in low rectal cancer. With the miniaturization and integration of colonoscopy or probes, MPM has the potential to provide real-time noninvasive optical diagnosis for surgical margins in low rectal cancer in the near future.

Evidence for A1 and A 3 receptors mediating adenosine-induced intracellular calcium release in the dorsal root ganglion neurons by using confocal microscopy imaging.

Adenosine exerts a key role in analgesia. In the present study, adenosine-induced Ca(2+) responses were revealed by using confocal microscopy imaging in the rat dorsal root ganglia (DRG) neurons in vitro. Our results showed that adenosine could evoke increases in the intracellular Ca(2+) concentration in the DRG neurons. In addition, by application of selective receptor antagonists, two types of receptors, A1R and A3R, were identified to be involved in the adenosine-induced Ca(2+) release from intracellular stores in neurons. Altogether, these results suggest that confocal microscopy imaging combined with fluorescent dyes could help to detect the analgesic-induced ion signaling in single cell.

Mechanism study of laser cochleostomy-induced early hearing loss in a rat model.

Hearing loss following laser-assisted ear surgery has been reported. However, the mechanism responsible for the hearing loss remains largely speculative. The aim of this study was to investigate the correlation between laser-induced hearing loss and changes in the number of hair cell ribbon synapses and ultrastructure in the cochlea. Laser cochleostomy was performed with a superpulsed carbon dioxide (CO2) laser at 2 and 5 W in Sprague-Dawley rats. Auditory brainstem responses (ABRs) were measured preoperatively and 2 days after surgery. The synapse numbers in apical and middle cochlear turns were quantified. Transmission electron microscopy was employed to further examine the subcellular changes in the cochlea. Click and tonal ABR threshold shifts in both 2 and 5-W groups displayed a frequency-dependent loss within the frequency range measured. Laser cochleostomy induced a significant decrease of synapse numbers in the middle turn in both groups (p < 0.05). Electron microscopy data indicated varying degrees of auditory nerve degeneration in both groups. Auditory nerve degeneration might contribute to laser-caused hearing loss even under low-energy laser cochleostomy. The high-energy laser-induced hearing loss was associated with more reduction of synapse number.

Feasibility study on quantitative measurements of singlet oxygen generation using singlet oxygen sensor green.

The purpose of this study is to investigate the feasibility for quantitative measurement of singlet oxygen ((1)O(2)) generation by using a newly developed (1)O(2)-specific fluorescence probe Singlet Oxygen Sensor Green reagent (SOSG). (1)O(2) generation from photoirradiation of a model photosensitizer Rose Bengal (RB), in initially air-statured phosphate buffered saline (PBS) was indirectly monitored with SOSG. In the presence of (1)O(2), SOSG can react with (1)O(2) to produce SOSG endoperoxides (SOSG-EP) that emit strong green fluorescence with the maximum at 531 nm. The green fluorescence of SOSG-EP is mainly dependent on the initial concentrations of RB and SOSG, and the photoirradiation time for (1)O(2) generation. Furthermore, kinetic analysis of the RB-sensitized photooxidation of SOSG is performed that, for the first time, allows quantitative measurement of (1)O(2) generation directly from the determination of reaction rate. In addition, the obtained (1)O(2) quantum yield of porphyrin-based photosensitizer hematoporphyrin monomethyl ether (HMME) in PBS by using SOSG is in good agreement with the value that independently determined by using direct measurement of (1)O(2) luminescence. The results of this study clearly demonstrate that the quantitative measurement of (1)O(2) generation using SOSG can be achieved by determining the reaction rate with an appropriate measurement protocol.

[Low level laser irradiation in the visible spectra induces HeLa cells proliferation].

The aim of this in vitro study was to evaluate the effects of low level laser irradiation on the proliferation of HeLa cells using 405 nm diode laser, 514 nm argon laser, 633 nm He-Ne laser, or 785 nm diode laser, The cells were seeded on 96-well microplates for 24 h in 5% fetal bovine serum containing medium, then irradiated with the laser at dose of 100 and 1 000 J x m(-2), respectively. At the time point of 24, 48, 72 h after irradiation, cell viability was assessed by MTT assay. The results show that 405, 633 and 785 nm laser irradiation induces wavelength-dependent and time-dependent proliferation. 633 nm laser irradiation results in a stimulatory proliferation effect that is most significant, whereas 514 nm laser irradiation produces little increase in cell proliferation. Low level laser irradiation increases cell proliferation in a dose-dependent manner. 1 000 J x m(-2) laser irradiation is more effective in increasing cell proliferation than 100 J x m(-2) laser irradiation using 405 nm diode laser, 633 nm He-Ne laser, or 785 nm diode laser, but not as effective as using 514 nm argon laser.

[Comparative study of time-correlated temperature and back-scattered light intensity for human Hegu acupoint and non-acupoint tissue irradiated by near-infrared laser].

Characteristics and differences of temperature and back-scattered light intensity in different depths of 0.2, 0.4, 0.6, 0.8 and 1 mm for both human Hegu acupoint and non-acupoint tissue irradiated by 808 nm diode laser at the different power of 15, 25 and 35 mW were studied. The temperature and the back-scattered light intensity in different depths of 0.2, 0.4, 0.6, 0.8 and 1 mm for human Hegu acupoint and non-acupoint tissue were measured by using the infrared thermography and optical coherence tomography. The result shows few differences in the temperature and the back-scattered light intensity of human Hegu acupoint and non-acupoint tissue before irradiation. The temperature and back-scattered light intensity of Hegu acupoint and the non-acupoint after irradiation were significantly higher, and the temperature and back-scattered light intensity of Hegu acupoint significantly were higher than the non-acupoint areas. At 0-40 min after the irradiation, the temperature and back-scattered light intensity of Hegu acupoint and the non-acupoint area will fluctuate and gradually decrease with the passage of time. From the results above, it is clearly seen that Hegu acupoint is different from non-acupoint both in the back-scattered light intensity and temperature after irradiation, and Hegu acupoint is more sensitive to laser irradiation than non-acupoint tissue.

Label-free surface enhanced Raman spectroscopy analysis of blood serum via coffee ring effect for accurate diagnosis of cancers.

Surface-enhanced Raman spectroscopy (SERS) is considered as an ultrasensitive, non-invasive as well as rapid detection technology for cancer diagnosis. In this study, we developed a novel blood serum analysis strategy using coffee ring effect-assisted label-free SERS for different types of cancer screening. Additionally, the pretreated Ag nanoparticles (Ag NPs) were mixed with the serum from liver cancer patients (n = 40), prostate cancer patients (n = 32) and healthy volunteers (n = 30) for SERS measurement. The droplets of Ag NPs-serum mixture formed the coffee ring on the peripheral after air-drying, and thus extremely enhancing Raman signal and ensuring the stability and reliability of SERS detection. Partial least square (PLS) and support vector machine (SVM) algorithms were utilized to establish the diagnosis model for SERS spectra data classifying, yielding the high diagnostic accuracy of 98.04% for normal group and two types of cancers simultaneously distinguishing. More importantly, for the unknown testing set, an ideal diagnostic accuracy of 100% could be achieved by PLS-SVM algorithm for differentiating cancers from the normal group. The results from this exploratory work demonstrate that serum SERS detection combined with PLS-SVM diagnostic algorithm and coffee ring effect has great potential for the noninvasive and label-free detection of cancer.

Study on degranulation of mast cells under C48/80 treatment by electroporation-assisted and ultrasound-assisted surface-enhanced Raman spectrascopy.

Both electroporation-assisted and ultrasound-assisted delivery methods can rapidly deliver nanoparticles into living cells for surface-enhanced Raman scattering (SERS) detection, but these two methods have never been compared. In this study, electroporation-assisted SERS and ultrasound-assisted SERS were employed to detect the biochemical changes of degranulated mast cells induced by mast cell stimulator (C48/80). The results showed that the cell damage of electroporation based on controllable electric pulse was smaller than that of ultrasound based on cavitation. Transmission electron microscope images of cells indicated that the nanoparticles delivered by electroporation were mainly distributed in the cytoplasm, while ultrasound could transport nanoparticles to the cytoplasm and nucleus. Therefore, electroporation-assisted SERS mainly detects the biochemical information of cytoplasm, while ultrasound-assisted SERS gets more spectral signals of nucleic acid. Both methods can obtain high quality SERS signal of cells. With drug treatment, the SERS peak intensity of 733 cm-1 attributed to phosphatidylserine decreased significantly, which may be due to the activation of mast cell degranulation pathway stimulated by C48/80 agonist, resulting in a large amount of intracellular serine being used to synthesize tryptase, while the production of phosphatidylserine decreased. Further, based on principal component analysis and linear discriminant analysis (PCA-LDA approach), ultrasound-assisted SERS could achieve better sensitivity, specificity and accuracy in the discrimination and identification of drug-treated degranulated mast cells than electroporation assisted SERS. This exploratory work is helpful to realize the real-time dynamic SERS detection of intracellular biochemical components, and it also has great potential in intracellular SERS analysis, such as the cytotoxicity assay of anti-tumor drugs or cancer cell screening.